VA/DoD CLINICAL PRACTICE GUIDELINE FOR 

THE MANAGEMENT OF TYPE 2 DIABETES 

MELLITUS IN PRIMARY CARE

Department of Veterans Affairs

Department of Defense

QUALIFYING STATEMENTS

The Department of Veterans Affairs and the Department of Defense guidelines are based upon the best 

information available at the time of publication. They are designed to provide information and assist 

decision-making. They are not intended to define a standard of care and should not be construed as 

one. Neither should they be interpreted as prescribing an exclusive course of management.

This Clinical Practice Guideline is based on a systematic review of both clinical and epidemiological 

evidence. Developed by a panel of multidisciplinary experts, it provides a clear explanation of the logical 

relationships between various care options and health outcomes while rating both the quality of the 

evidence and the strength of the recommendations.

Variations in practice will inevitably and appropriately occur when clinicians take into account the needs 

of individual patients, available resources, and limitations unique to an institution or type of practice. 

Every healthcare professional making use of these guidelines is responsible for evaluating the 

appropriateness of applying them in the setting of any particular clinical situation. 

These guidelines are not intended to represent Department of Veterans Affairs or TRICARE policy. 

Further, inclusion of recommendations for specific testing and/or therapeutic interventions within these 

guidelines does not guarantee coverage of civilian sector care. Additional information on current 

TRICARE benefits may be found at www.tricare.mil or by contacting your regional TRICARE Managed 

Care Support Contractor. 

Version 5.0 – 2017 

April 2017 Page 1 of 160 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 2 of 160

Prepared by:

The Management of Type 2 Diabetes Mellitus in Primary Care

Work Group

With support from:

The Office of Quality, Safety and Value, VA, Washington, DC

& 

Office of Evidence Based Practice, U.S. Army Medical Command

Version 5.0 – 2017 

Based on evidence reviewed through March 2016
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 3 of 160

Table of Contents

I. Introduction............................................................................................................................. 5

II. Background.............................................................................................................................. 5

A. Description of Diabetes Mellitus................................................................................................ 5

B. Epidemiology and Impact........................................................................................................... 7

III. About this Clinical Practice Guideline........................................................................................ 8

A. Methods...................................................................................................................................... 8

B. Summary of Patient Focus Group Methods and Findings........................................................ 12

C. Conflict of Interest.................................................................................................................... 13

D. Scope of this Clinical Practice Guideline................................................................................... 14

E. Highlighted Features of this Clinical Practice Guideline........................................................... 15

F. Shared Decision-making and Patient-centered Care................................................................ 15

G. Implementation........................................................................................................................ 16

IV. Guideline Work Group............................................................................................................17

V. Algorithm...............................................................................................................................18

A. Algorithm.................................................................................................................................. 19

VI. Recommendations .................................................................................................................21

A. General Approach to T2DM Care ............................................................................................. 23

B. Glycemic Control Targets and Monitoring................................................................................ 28

C. Non-pharmacological Treatments............................................................................................ 36

D. Inpatient Care ........................................................................................................................... 41

E. Selected Complications............................................................................................................. 46

VII. Pharmacological Therapy........................................................................................................52

A. Summary of the Evidence - Monotherapy and Non-Insulin Two-Drug Combination

Therapy..................................................................................................................................... 54

B. Triple Therapy........................................................................................................................... 56

C. Insulin Therapy ......................................................................................................................... 57

D. Cardiovascular Outcomes Trials ............................................................................................... 61

VIII. Knowledge Gaps and Recommended Research .......................................................................65

Appendix A: Evidence Review Methodology..................................................................................67

A. Developing the Scope and Key Questions................................................................................ 67

B. Conducting the Systematic Review .......................................................................................... 71
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 4 of 160

C. Convening the Face-to-face Meeting ....................................................................................... 75

D. Grading Recommendations...................................................................................................... 76

E. Recommendation Categorization............................................................................................. 79

F. Drafting and Submitting the Final Clinical Practice Guideline.................................................. 81

Appendix B: Pharmacotherapy......................................................................................................83

A. Alpha-glucosidase inhibitors..................................................................................................... 83

B. Amylin analog ........................................................................................................................... 84

C. Biguanides................................................................................................................................. 85

D. Dipeptidyl-peptidase 4 inhibitors............................................................................................. 86 

E. Glucagon-like 1 peptide receptor agonists............................................................................... 87

F. Insulin ....................................................................................................................................... 88

G. Meglitinides.............................................................................................................................. 89

H. Sodium glucose co-transporter 2 (SGLT2) inhibitors................................................................ 90

I. Sulfonylureas............................................................................................................................ 91

J. Thiazolidinediones.................................................................................................................... 92

Appendix C: FDA Approved/ Studied Combination Therapy............................................................93

Appendix D: Patient Focus Group Methods and Findings ...............................................................94

A. Methods.................................................................................................................................... 94

B. Patient Focus Group Findings................................................................................................... 95

Appendix E: Evidence Table..........................................................................................................97

Appendix F: 2010 Recommendation Categorization Table ...........................................................101

Appendix G: Participant List........................................................................................................131

Appendix H: Literature Review Search Terms and Strategy ..........................................................133

A. Topic-specific Search Terms ................................................................................................... 133

Appendix I: Acronym List...........................................................................................................148

References.....................................................................................................................................151
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 5 of 160

I. Introduction

The Department of Veterans Affairs (VA) and Department of Defense (DoD) Evidence-Based Practice 

Work Group (EBPWG) was established and first chartered in 2004, with a mission to advise the “...Health 

Executive Council on the use of clinical and epidemiological evidence to improve the health of the 

population across the Veterans Health Administration and Military Health System,” by facilitating the 

development of clinical practice guidelines for the VA and DoD populations.[1] This clinical practice 

guideline (CPG) is intended to provide healthcare providers with a framework by which to evaluate, 

treat, and manage the individual needs and preferences of patients with diabetes mellitus (DM), thereby 

leading to improved clinical outcomes.

The first VA/DoD CPG for the Management of Diabetes Mellitus, based upon earlier iterations in 1997 

and 2000, was published in 2003.[2] It established a risk stratification approach for setting individualized 

target goals based upon life expectancy, comorbid conditions, patient preferences, and absolute 

benefits and potential risks of therapy.[2] It also emphasized the risks of hypoglycemia. In 2010, the VA 

and DoD published a CPG for the Management of Diabetes Mellitus (2010 DM CPG), which was based on 

evidence reviewed through June 2009. Since the release of that guideline, a growing body of research 

has expanded the general knowledge and understanding of DM. Follow-up of major clinical trials of 

intensive therapy, as well as advances in physiological, behavioral, nutritional, and pharmacological 

research have led to the emergence of new strategies to manage and treat patients with DM.

Consequently, a recommendation to update the 2010 DM CPG was made and the update to the 2010 

DM CPG was initiated in 2015. The updated CPG includes evidence-based recommendations and 

additional information on the management of DM. It is intended to assist healthcare providers in all 

aspects of patient care, including diagnosis, treatment, and follow-up. The system-wide goal of 

evidence-based guidelines is to improve the patient’s health and well-being by guiding health providers, 

especially in primary care, to the management pathways that are supported by evidence. The expected 

outcome of successful implementation of this guideline is to:

• Emphasize shared decision-making to establish patient goals

• Assess the patient’s situation and determine, in collaboration with the patient, the treatment

methods to achieve the goals.

• Reduce the risk of preventable complications while improving quality of life (QoL).

II. Background

A. Description of Diabetes Mellitus

Diabetes mellitus is a disease caused by an absolute or relative insulin deficiency resulting in

hyperglycemia. Type 1 DM (T1DM) is due to insulin secretion deficiency not resulting from insulin 

resistance, while type 2 DM (T2DM) is due to insulin resistance that can eventually also result in insulin 

secretion deficiency. The insulin resistance resulting in T2DM is thought to be due to excess adiposity, 

especially central distribution of adiposity, but can be due to other factors, such as corticosteroid 

treatment or Cushing’s syndrome. Gestational diabetes (GDM) is DM present during pregnancy. Other 

more unusual types of DM also exist, such as maturity onset diabetes of the young (MODY), latent 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 6 of 160

autoimmune diabetes of adult (LADA) and those related to pancreatic disease or acromegaly, but the

current guideline is focused on T2DM.

Several criteria exist to diagnose T2DM and prediabetes based on biomarker levels. The criteria used by

this Work Group are summarized in Table 1. Prediabetes is a condition where blood glucose levels are

higher than normal but the patient does not meet the criteria for DM.[3] Hyperglycemia not sufficient to

meet the diagnostic criteria for DM has historically been categorized as either impaired fasting glucose

(IFG), or impaired glucose tolerance (IGT) depending on the methodology through which it is identified.

The use of hemoglobin A1c (HbA1c) in the diagnosis of diabetes is derived from a study of the linear 

relationship between HbA1c values and microvascular complications, specifically retinopathy, with the 

diagnostic level occurring at the inflection point of rise in incidence. However, differences among

laboratories in the acceptable variability of HbA1c test values, as well as evidence suggesting that there

may be racial/ethnic differences, suggests that reliance upon HbA1c test results alone are not congruent 

with fasting blood glucose levels.[4,5] Racial differences were reported among participants in the

Diabetes Prevention Program. Despite having comparable measures of glycemia, African Americans had

significantly higher HbA1c levels (6.2%) than Whites (5.8%).[6] The VA/DoD DM CPG recommends that 

HbA1c values between 6.5%-7.0% be confirmed with fasting plasma glucose levels to improve diagnostic

specificity.

Table 1: Criteria for the diagnosis of diabetes mellitus and prediabetes [6]

Status Fasting Plasma Glucose 1,2 or Hemoglobin A1c 3

Diabetes Mellitus

FPG ≥ 126 mg/dL (7.0 mmol/L) on two occasions

OR

HbA1c ≥ 6.5% with a confirmatory FPG ≥ 126 mg/dL (7.0 mmol/L)

OR

HbA1c ≥ 7.0% on two occasions

FPG ≥ 100 mg/dL and < 126 mg/dL on two occasions

OR

Prediabetes

OR

HbA1c ≥ 5.7% and FPG ≥ 100 mg/dL and < 126 mg/dL (7.0 mmol/L)

2-hr plasma glucose 140-199 mg/dL (7.8-11.0 mmol/L) (IGT)

Normal FPG < 100 mg/dL

HbA1c < 5.7%

Abbreviations: dL: deciliter; FPG: fasting plasma glucose; HbA1c: hemoglobin A1c; hr: hour; IGT: impaired glucose tolerance; 

L: liter; mg: milligram; mmol: millimole 

1 Fasting is defined as no caloric intake for at least eight hours. 2 FPG is the preferred test for diagnosis, but either of the two listed is acceptable. In the absence of unequivocal hyperglycemia

with acute metabolic decompensation, one of these two tests should be done on different days.

3 Using a clinical laboratory (not a point-of-care) methodology standardized to the National Glycohemoglobin Standardization 

Program (NGSP)

An oral glucose tolerance testing (OGTT) is most commonly done to diagnose gestational diabetes. 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 7 of 160

Patients with one or more of the following risk factors are at higher risk for T2DM: 

• Age ≥ 45 years

• Family history (first-degree relative with DM)

• Member of a high-prevalence population (e.g., African American, Hispanic American, Native

American, Asian American, Pacific Islander)

• Prediabetes (HbA1c ≥ 5.7% [39 mmol/mol], fasting blood glucose 100-125 mg/dl IGT [7], or IFG

on previous testing)

1

• Hypertension (blood pressure ≥ 140/90 mmHg or on therapy for hypertension)

1

• High-density lipoprotein cholesterol (HDL-C) level < 35 mg/dL (0.90 mmol/L) and/or a triglyceride

(TG) level > 250 mg/dL (2.82 mmol/L)1

• History of cardiovascular disease (CVD)1

• Overweight (body mass index [BMI] ≥ 25 kg/m2 or ≥ 23 kg/m2 in Asian Americans)

1

• Abdominal obesity1

• Women with polycystic ovary syndrome (PCOS)1

• History of GDM or history of delivering babies weighing > 9 lbs (about 4 kg)

• Other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis

nigricans)

• Physical inactivity/sedentary lifestyle

• Patients using antipsychotics or statins

B. Epidemiology and Impact

The prevalence of diabetes is increasing around the world, mostly due to the increase in obesity and 

sedentary lifestyles.[8] The number of Americans with diagnosed DM has increased four-fold between 

1980 and 2014.[9] In the United States (U.S.), a total of 29.1 million people, or 9.3% of the population, 

have DM (type 1 or type 2), of which 21 million are diagnosed and 8.1 million are undiagnosed.[10] 

In the military population enrolled in the Military Health System (MHS), the prevalence of diagnosed DM 

ranged from 7.3% to 11.2% in 2006 and from 8.3% to 13.6% in 2010.[11] Although the prevalence 

among Active Duty Service Members remained stable, a significant increase was observed over time 

among Non-Active Duty Service Members.[11] In 2010, the prevalence among Non-Active military men 

and women were 15.0% and 13.3% respectively for those aged 45-64 years, 32.9% and 26.9% respectively 

for those aged 65-74 years, and 31.5% and 25.7% respectively for those aged 75 years and older.[11]

According to the Veterans Health Administration (VHA), nearly one in four Veterans (1.6 million 

individuals) who are receiving care from the VA has DM. Veterans 65 years and older comprise 70% of 

those with diabetes, reflecting the older age distribution of this population.[12] 

1 Associated with insulin resistance
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 8 of 160

DM can cause microvascular complications such as retinopathy, nephropathy, and neuropathy as well as 

macrovascular complications, including ischemic heart disease, stroke, and peripheral vascular 

disease.[13] In addition to the complications of T2DM, conditions such as chronic obstructive pulmonary 

disease (COPD), substance use disorder (SUD), and depression can affect the management of DM. For 

guidance on how to address those comorbidities, see the respective VA/DoD Clinical Practice Guidelines 

for the Management of COPD, SUD and Major Depressive Disorder (MDD).

2,3,4 DM is a major cause of 

morbidity and mortality in the U.S. It is associated with a two-fold to four-fold increased risk for 

atherosclerotic CVD, resulting in substantial morbidity and mortality from coronary events. For the 

management of CVD risk factors, refer to the VA/DoD Clinical Practice Guidelines for the Management 

of Hypertension, Chronic Kidney Disease (CKD), and Dyslipidemia.

5,6,7 The total costs of diagnosed DM in 

the U.S. were $245 billion in 2012, including $176 billion for direct medical costs and $69 billion in 

reduced productivity.[14] Direct costs in the VHA and MHS are not known.

III. About this Clinical Practice Guideline

This guideline represents a significant step toward improving the treatment and management of 

patients with DM in the VA and DoD. As with other CPGs, however, challenges remain, including 

evidence gaps, the need to develop effective strategies for guideline implementation and to evaluate 

the effect of guideline adherence on clinical outcomes. This guideline is intended for VA and DoD 

healthcare practitioners including physicians, nurse practitioners, nurses, physician assistants, 

dietitians/nutritionists, diabetes educators, pharmacists, and others involved in the care of Service 

Members or Veterans with DM.

As elaborated in the qualifying statement on page one, this CPG is not intended to serve as a standard of 

care. Standards of care are determined on the basis of all clinical data available for an individual patient

and are subject to change as scientific knowledge and technology advance and patterns evolve. This CPG 

is based on information available by March 2016 and is intended to provide a general guide to best 

practices. The guideline can assist care providers, but the use of a CPG must always be considered as a 

recommendation, within the context of a provider’s clinical judgment and patient values and 

preferences, for the care of an individual patient.

A. Methods

The current document is an update to the 2010 DM CPG. The methodology used in developing the 2017 

CPG follows the Guideline for Guidelines,[1] an internal document of the VA and DoD EBPWG. The 

2 See the VA/DoD Clinical Practice Guideline for the Management of Chronic Obstructive Pulmonary Disease (COPD). Available 

at: http://www.healthquality.va.gov/guidelines/CD/copd/

3 See the VA/DoD Clinical Practice Guideline for the Management of Substance Use Disorders (SUD). Available at: 

http://www.healthquality.va.gov/guidelines/MH/sud/

4 See the VA/DoD Clinical Practice Guideline for the Management of Major Depressive Disorder (MDD). Available at: 

http://www.healthquality.va.gov/guidelines/MH/mdd/

5 See the VA/DoD Clinical Practice Guideline for the Diagnosis and Management of Hypertension in Primary Care. Available at: 

http://www.healthquality.va.gov/guidelines/CD/htn/

6 See the VA/DoD Clinical Practice Guideline for the Management of Chronic Kidney Disease (CKD) in Primary Care. Available at: 

http://www.healthquality.va.gov/guidelines/CD/ckd/

7 See the VA/DoD Clinical Practice Guideline for the Management of Dyslipidemia for Cardiovascular Risk Reduction. Available at: 

http://www.healthquality.va.gov/guidelines/CD/lipids/
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 9 of 160

Guideline for Guidelines can be downloaded from http://www.healthquality.va.gov/policy/index.asp. 

This document provides information regarding the process of developing guidelines, including the 

identification and assembly of the Guideline Champions (Champions), and other subject matter experts 

from within the VA and DoD, known as the Work Group, and ultimately, the development and 

submission of a new or updated DM CPG.

The Champions and Work Group for this CPG were charged with developing evidence-based clinical 

practice recommendations and writing and publishing a guideline document to be used by providers 

within the VA/DoD healthcare systems. Specifically, the Champions and Work Group members for this

guideline were responsible for identifying the key questions (KQs) of the most clinical relevance, 

importance, and interest for the management of patients with DM. The Champions and the Work Group 

also provided direction on inclusion and exclusion criteria for the evidence review and assessed the level 

and quality of the evidence. The amount of new scientific evidence that had accumulated since the 

previous version of the CPG was also taken into consideration in the identification of the KQs. In 

addition, the Champions assisted in:

• Identifying appropriate disciplines of individuals to be included as part of the Work Group

• Directing and coordinating the Work Group

• Participating throughout the guideline development and review processes

The VA Office of Quality, Safety and Value, in collaboration with the Office of Evidence Based Practice, U.S. 

Army Medical Command, the proponent for CPGs for the DoD, identified two clinical leaders as Champions 

for the 2017 DM CPG. Leonard Pogach, MD, MBA is the Champion from the VA and Maj Jeffrey A. Colburn, 

MD is the Champion for the DoD. Maj Colburn replaced the previous DoD Champion who left the Work 

Group after the in-person Work Group meeting in June 2016 due to a conflict of interest (COI). 

The Lewin Team, including the Lewin Group, Duty First Consulting, ECRI Institute, and Sigma Health 

Consulting, LLC, was contracted by the VA and DoD to support the development of this CPG and conduct 

the evidence review. The first conference call was held in December 2015, with participation from the 

contracting officer’s representative, leaders from the VA Office of Quality, Safety and Value and the DoD 

Office of Evidence Based Practice, and the Champions. During this call, participants discussed the scope 

of the guideline initiative, the roles and responsibilities of the Champions, the project timeline, and the 

approach for developing and prioritizing specific research questions on which to base a systematic 

review (SR) about the management of DM. The group also identified a list of clinical specialties and 

areas of expertise that are important and relevant to the management of DM, from which Work Group 

members were recruited. The specialties and clinical areas of interest included endocrinology, internal 

medicine, nutrition, pharmacy, health education, nursing, medical management, ambulatory care, and 

family practice.

The guideline development process for the 2017 CPG update consisted of the following steps:

1. Formulating and prioritizing KQs

2. Conducting a patient focus group

3. Conducting the SR
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 10 of 160

4. Convening a face-to-face meeting with the Champions and Work Group members

5. Drafting and submitting a final CPG about the management of DM to the VA/DoD EBPWG

Appendix A provides a detailed description of each of these tasks.

a. Grading Recommendations

The Champions and Work Group used the Grading of Recommendations Assessment, Development and 

Evaluation (GRADE) system to assess the quality of the evidence base and assign a grade for the strength 

for each recommendation. The GRADE system uses the following four domains to assess the strength of 

each recommendation:[15]

• Confidence in the quality of the evidence 

• Balance of desirable and undesirable outcomes 

• Patient or provider values and preferences

• Other implications, as appropriate, e.g.,:

 Resource use

 Equity

 Acceptability

 Feasibility

 Subgroup considerations

Using this system, the Champions and Work Group determined the relative strength of each 

recommendation (Strong or Weak). A strong recommendation indicates that the Work Group is highly 

confident that desirable outcomes outweigh undesirable outcomes. If the Work Group is less confident 

of the balance between desirable and undesirable outcomes, they give a weak recommendation.

They also determined the direction of each recommendation (For or Against). Similarly, a 

recommendation for a therapy or preventive measure indicates that the desirable consequences 

outweigh the undesirable consequences. A recommendation against a therapy or preventive measure 

indicates that the undesirable consequences outweigh the desirable consequences.

Using these elements, the grade of each recommendation is presented as part of a continuum:

• Strong For (or “We recommend offering this option ...”)

• Weak For (or “We suggest offering this option ...”)

• Weak Against (or “We suggest not offering this option ...”)

• Strong Against (or “We recommend against offering this option ...”)

The grade of each recommendation made in the 2017 DM CPG can be found in the section on 

Recommendations. Additional information regarding the use of the GRADE system can be found in 

Appendix A.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 11 of 160

It is important to note that the GRADE system grades the strength of recommendations based on four 

domains—(1) confidence in the quality of evidence; (2) balance of benefits and harms; (3) patient values 

and preferences; and (4) other considerations, which can include resource use, equity and acceptability. 

Most other grading systems, such as U.S. Preventive Services Task Force (USPSTF), use only two 

domains—(1) certainty of net benefit and (2) magnitude of net benefit (i.e., balance of benefits and 

harms). Thus, differences in recommendations across guidelines may reflect differences in the grading 

system used as well as differences in the evidence reviewed and/or how the strength of the evidence is 

evaluated by the Work Group.

b. Reconciling 2010 Clinical Practice Guideline Recommendations

Evidence-based CPGs should be current, which typically requires revisions of previous guidelines based 

on new evidence, or as scheduled, subject to time-based expirations.[16] For example, the USPSTF has a 

process for refining or otherwise updating its recommendations pertaining to preventive services.[17]

Further, the inclusion criteria for the National Guideline Clearinghouse specify that a guideline must 

have been developed, reviewed, or revised within the past five years. 

The DM Guideline Work Group focused largely on developing new and updated recommendations 

based on the evidence review conducted for the priority areas addressed by the KQs. In addition to 

those new and updated recommendations, the Guideline Work Group considered, without complete 

review of the relevant evidence, the current applicability of other recommendations that were included 

in the previous 2010 DM CPG, subject to evolving practice in today’s environment. 

A set of recommendation categories was adapted from those used by the National Institute for Health 

and Care Excellence (NICE).[18,19] These categories, along with their corresponding definitions, were 

used to account for the various ways in which previous recommendations could have been updated. In 

brief, the categories took into account whether or not the evidence that related to a recommendation 

was systematically reviewed, the degree to which the recommendation was modified, and the degree to 

which a recommendation is relevant in the current patient care environment and within the scope of 

the CPG. Additional information regarding these categories and their definitions can be found in 

Appendix A. The categories for the recommendations included in the 2017 version of the guideline can 

be found in the section on Recommendations. The categories for the recommendations from the 2010 

DM CPG are noted in Appendix F.

The CPG Work Group recognized the need to accommodate the transition in evidence-rating systems 

from the 2010 DM CPG to the current CPG. In order to report the strength of all recommendations using 

a consistent format (i.e., the GRADE system), the CPG Work Group converted the USPSTF strengths of 

the recommendation accompanying the carryover recommendations from the 2010 guideline to the 

GRADE system. As such, the CPG Work Group considered the strength of the evidence cited for each 

recommendation in the 2010 DM CPG as well as harms and benefits, values and preferences, and other 

implications, where possible. The CPG Work Group referred to the available evidence as summarized in 

the body of the 2010 DM CPG and did not re-assess the evidence systematically. In some instances, 

peer-reviewed literature published since the 2010 DM CPG was considered along with the evidence base 

used for that CPG.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 12 of 160

Where such newer literature was considered when converting the strength of the recommendation 

from the USPSTF to the GRADE system, it is referenced in the discussion that follows the corresponding 

recommendation, as well as in Appendix E.

The CPG Work Group recognizes that, while there are practical reasons for incorporating findings from a 

previous SR, previous recommendations,[20] or recent peer-reviewed publications into an updated CPG, 

doing so does not involve an original, comprehensive SR and, therefore, may introduce bias. 

c. Peer Review Process 

The CPG was developed through an iterative process in which the Work Group produced multiple drafts 

of the CPG. The process for developing the initial draft is described in more detail in Drafting and 

Submitting the Final Clinical Practice Guideline. 

Once a near-final draft of the guideline was agreed upon by the Champions and Work Group members, 

the draft was sent out for peer review and comment. The draft was posted on a wiki website for a 

period of 14 business days. The peer reviewers comprised individuals working within the VA and DoD 

health systems as well as experts from relevant outside organizations designated by the Work Group 

members. External organizations that participated in the peer review included the following:

• Academy of Nutrition and Dietetics

• Center for Drug Evaluation and Research, U.S. Food and Drug Administration (FDA)

• Coverage and Analysis Group, Centers for Medicare and Medicaid Services (CMS)

• Geisel School of Medicine, Dartmouth College

• Health Resources and Services Administration (HRSA)

• National Institute on Aging, National Institutes of Health (NIH)

• Office of Rural Health Policy, U.S. Department of Health and Human Services (HHS)

The VA and DoD Leadership reached out to both the internal and external peer reviewers to solicit their 

feedback on the CPG. Reviewers were provided a hyperlink to the wiki website where the draft CPG was 

posted. For transparency, all reviewer feedback was posted in tabular form on the wiki site, along with 

the name of the reviewer. All feedback from the peer reviewers was discussed and considered by the 

Work Group. Modifications made throughout the CPG development process were made in accordance 

with the evidence.

B. Summary of Patient Focus Group Methods and Findings

When forming guideline recommendations, consideration should be given to the values of those most 

affected by the recommendations. Patients bring perspectives, values, and preferences into their 

healthcare experience, and more specifically their DM care experience, that vary from those of 

clinicians. These differences and the variability between patients’ perspectives can affect decision 

making in various situations, and should thus be highlighted and made explicit due to their potential to 

influence a recommendation’s implementation.[21,22] Focus groups can be used as an efficient method 

to explore ideas and perspectives of a group of individuals with an a priori set of assumptions or 

hypotheses and collect qualitative data on a thoughtfully predetermined set of questions. 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 13 of 160

Therefore, as part of the effort to update this CPG, VA and DoD Leadership, along with the DM CPG 

Work Group and Lewin, held a patient focus group on March 8, 2016, at the VA Puget Sound Health Care 

System - American Lake Division in Tacoma, Washington. The aim of the focus group was to further the 

understanding of the perspective of patients receiving treatment for DM within the VA and/or DoD 

healthcare systems. The focus group explored patient perspectives on a set of topics related to 

management of DM in the VA and DoD healthcare systems, including patients’ knowledge of DM 

treatment options, views on the delivery of care, patients’ perspective on their needs and preferences, 

and the impact of DM on their lives.

It is important to note the focus group was a convenience sample and the Working Group recognizes the 

limitations inherent in the small sample size. Less than 10 people were included in the focus group 

consistent with the requirements of the federal Paperwork Reduction Act, 1980. The Work Group 

acknowledges that the sample of patients included in this focus group may not be representative of all 

VA and DoD patients receiving treatment for DM. Patient perspective and input provided, while 

invaluable, is not generalizable given the broad characteristics of various key demographic groups of 

persons with DM. Further, time limitations for the focus group prevented exhaustive exploration of all 

topics related to DM treatment in the VA and DoD and the patients’ broader experiences with their care. 

Thus, the Working Group made decisions regarding the priority of topics to discuss at the focus group. 

These limitations, as well as others, were considered throughout the use of the information collected 

from the discussion for guideline development. 

Recruitment for participation in the focus group was managed by the Champions and VA and DoD 

Leadership, with assistance from coordinators at the facility at which the focus group took place. 

The following concepts are aspects of care that are important to patients that emerged from the 

discussion. These concepts were needed and important parts of the participants’ care and added to the 

Work Group’s understanding of patient values and perspectives. Additional details regarding the patient 

focus group methods and findings can be found in Appendix D.

DM CPG Patient Focus Group Concepts

A. Using shared decision-making, consider all treatment options and develop a treatment plan based on the 

balance of risks, benefits, and patient-specific goals, values, and preferences.

B. Guide patients on the self-management of their DM and glucose monitoring, including benefits and risks, and 

their expectations.

C. Educate and involve family caregivers and co-workers in accordance with patient preferences regarding core 

knowledge of DM management.

D. Within and between VA and DoD healthcare systems, work with appropriate providers to ensure continuity of 

high-quality care and timely referral to an endocrinologist.

E. Create a support system for patients with DM such as online groups, chats, other support groups, and 

diabetes education classes to enhance involvement and support among patients with DM.

C. Conflict of Interest

At the start of this guideline development process and at other key points throughout, the project team 

was required to submit disclosure statements to reveal any areas of potential COI in the past 24 months. 

Verbal affirmations of no COI were used as necessary during meetings throughout the guideline 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 14 of 160

development process. The project team was also subject to random web-based surveillance (e.g., 

ProPublica). 

If a project team member reported a COI (actual or potential), measures were in place to mitigate the 

introduction of bias into the guideline development process. Identified COIs would be reported to the 

Office of Evidence Based Practice and disclosed to the EBPWG in tandem with their review of the 

evidence and development of recommendations. The EBPWG and the DM CPG Work Group would then 

determine whether or not action, such as restricting participation and/or voting on sections related to 

the conflict or removal from the Work Group, was necessary. If deemed necessary, action to mitigate 

the COI was taken by the Champions and Office of Evidence Based Practice, based on the level and 

extent of involvement. 

In order to mitigate the risk of bias while maximizing the contributions of those with expertise in a 

specific area of DM, the Champions asked Work Group members to disclose relevant relationships 

during related guideline development discussions. Members with potential COIs contributed to the 

discussions related to their particular areas of expertise as well as the overarching guideline document 

in order to ensure differing viewpoints and experiences were adequately represented.

The initially appointed DoD Champion disclosed a COI at the in-person meeting and VA and DoD 

Leadership determined the COI would preclude him from continuing his role on the DM CPG Work 

Group. Maj Jeffrey A. Colburn, already a DM CPG Work Group member, was selected as the new DoD

Champion. The work on the guideline when the initial DoD Champion was present was reviewed and 

steps were taken to ensure that no biases were introduced and that the initial work on the DM CPG with 

the former DoD Champion did not negatively affect the objectivity of the DM CPG development. 

D. Scope of this Clinical Practice Guideline

Regardless of setting, any patient in the VA/DoD healthcare systems should be offered access to the 

interventions that are recommended in this guideline after taking into consideration the patient’s specific 

circumstances. 

This CPG is designed to assist providers in managing or co-managing patients with T2DM. Moreover, the 

patient population of interest for this CPG is adults who are eligible for care in the VA and DoD 

healthcare delivery systems, which includes Veterans, deployed and non-deployed Active Duty Service 

Members, and their adult family members, and retirees and their beneficiaries or dependents. This CPG 

does not provide recommendations for the management of DM in children, adolescents, or 

pregnant/nursing women. 

The literature review encompassed interventional studies (primarily randomized controlled trials [RCTs]) 

and observational studies published between January 2009 and March 2016, and targeted nine KQs 

focusing on the means by which the delivery of healthcare could be optimized for patients with DM. 

KQ7 required updated searches through June 14, 2016. The selected KQs were prioritized from many 

possible KQs. Due to resource constraints, a review of the evidence in all important aspects of care for 

patients with DM was not feasible for the update of this CPG. For example, treatments specific to obese 

patients, such as bariatric surgery, are not addressed in this CPG but are addressed in the VA/DoD 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 15 of 160 

Clinical Practice Guideline for Screening and Management of Overweight and Obesity (VA/DoD Obesity 

CPG).8

E. Highlighted Features of this Clinical Practice Guideline

The 2017 edition of the VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes 

Mellitus in Primary Care is the fourth update to the original CPG. It provides practice recommendations 

for the care of patients with DM. A particular strength of this CPG is the multidisciplinary stakeholder 

involvement from its inception, ensuring representation from the broad spectrum of clinicians engaged 

in the treatment and management of patients with DM. 

The framework for recommendations in this CPG considered factors beyond the strength of the 

evidence, including balancing desired outcomes with potential harms of treatment, the potential for 

variation in patient values and preferences, and other considerations such as resource use and equity. 

Applicability of the evidence to VA/DoD populations was also taken into consideration. A structured 

algorithm accompanies the guideline to provide an overview of the recommendations in the context of 

the flow of patient care and clinician decision making and to assist with training providers. The algorithm 

may be used to help facilitate translation of guideline recommendations into effective practice.

F. Shared Decision-making and Patient-centered Care

Throughout this VA/DoD CPG, the authors encourage clinicians to focus on shared decision-making 

(SDM). The SDM model was introduced in Crossing the Quality Chasm, an Institute of Medicine (now the 

National Academy of Medicine) report, in 2001.[23] It is readily apparent that patients with DM, 

together with their clinicians, make decisions regarding their plan of care and target glycemic range; 

however, these patients require sufficient information to be able to make informed decisions. Clinicians 

must be skilled at presenting their patients with understandable and actionable information regarding 

both individual treatments and levels and locations of care. 

Therefore, the VA/DoD CPG recommendations are intended to promote SDM and be patient-centered. 

VA/DoD CPGs encourage clinicians to use SDM to individualize treatment goals and plans based on 

patient capabilities, needs, goals, prior treatment experience, and preferences. Good communication 

between healthcare professionals and the patient is essential and should be supported by evidencebased information tailored to the patient’s needs. Use of an empathetic and non-judgmental (versus a 

confrontational) approach facilitates discussions sensitive to gender, culture, and ethnic differences. The 

information that patients are given about treatment and care should be culturally appropriate and also 

available to people with limited literacy skills. It should also be accessible to people with additional 

needs such as physical, sensory, or learning disabilities. Family involvement should be considered if 

appropriate, especially in elderly patients.[24] When properly executed, SDM [25,26] may decrease 

patient anxiety, increase trust in clinicians,[27] and improve treatment adherence.[28] Improved 

patient-clinician communication can be used to convey openness to discuss any future concerns. 

As part of the patient-centered care approach, clinicians should review the outcomes of previous selfchange efforts, past treatment experiences, and outcomes (including reasons for treatment drop-out) 

 

8 See the VA/DoD Clinical Practice Guideline for Screening and Management of Overweight and Obesity. Available at: 

http://www.healthquality.va.gov/guidelines/CD/obesity/
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 16 of 160

with the patient. Lastly, they should involve the patient in prioritizing problems to be addressed and in 

setting specific goals regardless of the selected setting or level of care.

G. Implementation

This CPG and algorithm are designed to be adapted by individual healthcare providers with 

consideration of local needs and resources. The algorithm serves as a tool to prompt providers to 

consider key decision points in the course of an episode of care. 

Although this CPG represents the recommended practice on the date of its publication, medical practice 

is evolving and this evolution requires continuous updating based on published information. New 

technology and more research will improve patient care in the future. The CPG can assist in identifying 

priority areas for research and to inform optimal allocation of resources. Future studies examining the 

results of CPG implementation may lead to the development of new evidence particularly relevant to 

clinical practice. 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 17 of 160

IV. Guideline Work Group

Guideline Work Group*

Department of Veterans Affairs Department of Defense

Leonard Pogach, MD, MBA, FACP (Champion) Maj Jeffrey A. Colburn, MD, FACP (Champion)

David C. Aron, MD, MS Elizabeth Rees Atayde, RN, MSN, FNP, CCM, CPHM

Paul R. Conlin, MD Amy M. Lugo, PharmD, BCPS, BC-ADM, FAPhA

Mercedes Falciglia, MD, FACP Susan McReynolds, RD, CDE

Chester B. Good, MD, MPH, FACP Maj Tracy L. Snyder, MS, RD

Mary M. Julius, RDN, CDE Evan N. Steil, MD, MBA, MHA

Deborah Khachikian, PharmD Elaine P. Stuffel, RN, BSN, MHA

Rose Mary Pries, DrPH COL Gwendolyn H. Thompson, PharmD

Sharon A. Watts, DNP, FNP-BC, CDE LCDR Mark P. Tschanz, DO, MACM, FACP

Nina A. Watson, MSN, RN, CDE

Office of Quality, Safety and Value

Veterans Health Administration

Office of Evidence Based Practice

U.S. Army Medical Command

Eric Rodgers, PhD, RNP-BC

James L. Sall, PhD, FNP-BC

Rene Sutton, BS, HCA

Corinne K. B. Devlin, MSN, RN, FNP-BC

Elaine P. Stuffel, RN, BSN, MHA

Lewin Group ECRI Institute

Clifford Goodman, PhD

Christine Jones, MS, MPH, PMP

Raksha Adhikari, MSPH, CPH

Nicolas Stettler-Davis, MD, MSCE

Kristen E. D’Anci, PhD

Jane S. Jue, MD

Nancy M. Sullivan, BA

Edmond Baganizi, MPH

Oluwasean Akinyede, MPH

Eileen Erinoff, MSLIS

Sigma Health Consulting, LLC Duty First Consulting

Frances Murphy, MD, MPH Megan McGovern, BA

Anita Ramanathan, BA

*Additional contributor contact information is available in Appendix G.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 18 of 160

V. Algorithm

This CPG includes an algorithm which is designed to facilitate understanding of the clinical pathway and 

decision-making process used in management of DM. The use of the algorithm format as a way to 

represent patient management was chosen based on the understanding that such a format may 

promote more efficient diagnostic and therapeutic decision making and has the potential to change 

patterns of resource use. Recognizing that some clinical care processes are non-linear, the algorithm 

format allows the provider to follow a simplified linear approach in assessing the critical information 

needed at the major decision points in the clinical process, and includes:

• An ordered sequence of steps of care

• Relevant observations and examinations

• Decisions for consideration

• Actions to be taken

A clinical algorithm diagrams a guideline into a step-by-step decision tree. Standardized symbols are 

used to display each step in the algorithm and arrows connect the numbered boxes indicating the order 

in which the steps should be followed.[29] 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 19 of 160 

A. Algorithm 

a. Module A: General Care and Treatment 

Abbreviations: T2DM: Type 2 diabetes mellitus

*For sequential treatment of DM, see Figure 1

†Target range incorporates the known variation in the HbA1c test from the laboratory used by the patient

^Use the Teach-Back Method: Tool #5. Content last reviewed February 2015. Agency for Healthcare Research and Quality, Rockville, MD. 

http://www.ahrq.gov/professionals/quality-patient-safety/quality-resources/tools/literacy-toolkit/healthlittoolkit2-tool5.html
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 20 of 160 

b. Module B: Diabetes Self-Management Education 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 21 of 160

VI. Recommendations

# Recommendation Strength* Category†

A. General Approach to T2DM Care

1. We recommend shared decision-making to enhance patient knowledge 

and satisfaction.

Strong for Reviewed, 

New-added

2. We recommend that all patients with diabetes should be offered ongoing 

individualized diabetes self-management education via various modalities 

tailored to their preferences, learning needs and abilities based on 

available resources.

Strong for Reviewed, 

New-replaced

3. We suggest offering one or more types of bidirectional telehealth 

interventions (typically health communication via computer, telephone or 

other electronic means) involving licensed independent practitioners to 

patients selected by their primary care provider as an adjunct to usual 

patient care.

Weak for Reviewed, 

New-replaced

B. Glycemic Control Targets and Monitoring

4. We recommend setting an HbA1c target range based on absolute risk 

reduction of significant microvascular complications, life expectancy, 

patient preferences and social determinants of health. 

Strong for Reviewed, 

New-added

5. We recommend developing an individualized glycemic management plan, 

based on the provider’s appraisal of the risk-benefit ratio and patient 

preferences.

Strong for Reviewed, 

Amended

6. We recommend assessing patient characteristics such as race, ethnicity, 

chronic kidney disease, and non-glycemic factors (e.g., laboratory 

methodology and assay variability) when interpreting HbA1c, 

fructosamine and other glycemic biomarker results.

Strong for Reviewed, 

New-added

7. We recommend an individualized target range for HbA1c taking into 

account individual preferences, presence or absence of microvascular 

complications, and presence or severity of comorbid conditions (See Table

2). 

Strong for Reviewed, 

New-replaced

8. We suggest a target HbA1c range of 6.0-7.0% for patients with a life 

expectancy greater than 10-15 years and absent or mild microvascular 

complications, if it can be safely achieved (See Table 2).

Weak for Reviewed, 

New-replaced

9. We recommend that in patients with type 2 diabetes, a range of HbA1c 

7.0-8.5% is appropriate for most individuals with established 

microvascular or macrovascular disease, comorbid conditions, or 5-10

years life expectancy, if it can be safely achieved (See Table 2).

Strong for Reviewed, 

New-added

10. We suggest a target HbA1c range of 8.0-9.0% for patients with type 2 

diabetes with life expectancy <5 years, significant comorbid conditions, 

advanced complications of diabetes, or difficulties in self-management

attributable to e.g., mental status, disability or other factors such as food 

insecurity and insufficient social support. (See Table 2).

Weak for Reviewed, 

New-replaced

11. We suggest that providers be aware that HbA1c variability is a risk factor 

for microvascular and macrovascular outcomes.

Weak for Reviewed, 

New-added

C. Non-pharmacological Treatments

12. We recommend offering therapeutic lifestyle changes counseling that 

includes nutrition, physical activity, cessation of smoking and excessive 

use of alcohol, and weight control to patients with diabetes (See VA/DoD 

CPGs for obesity, substance use disorders, and tobacco use cessation). 

Strong for Not Reviewed, 

Amended
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 22 of 160

# Recommendation Strength* Category†

13. We recommend a Mediterranean diet if aligned to patient’s values and 

preferences.

Strong for Reviewed, 

New-added

14. We recommend a nutrition intervention strategy reducing percent of energy 

from carbohydrate to 14-45% per day and/or foods with lower glycemic 

index in patients with type 2 diabetes who do not choose the 

Mediterranean diet. 

Strong for Reviewed, 

New-added

D. Inpatient Care

15. We recommend against targeting blood glucose levels <110 mg/dL for all 

hospitalized patients with type 2 diabetes receiving insulin. 

Strong 

against

Reviewed, 

Amended

16. We recommend insulin be adjusted to maintain a blood glucose level

between 110 and 180 mg/dL for patients with type 2 diabetes in critically 

ill patients or those with acute myocardial infarction.

Strong for Reviewed, 

Amended

17. We recommend against the use of split mixed insulin regimen for all 

hospitalized patients with type 2 diabetes.

Strong 

against

Reviewed, 

New-added

18. We suggest a regimen including basal insulin and short-acting meal time or 

basal insulin and correction insulin for non-critically ill hospitalized 

patients with type 2 diabetes.

Weak for Reviewed, 

New-added

19. We suggest providing medication education and diabetes survival skills to 

patients before hospital discharge.

Weak for Reviewed, 

Amended

E. Selected Complications and Conditions

20. We recommend performing a comprehensive foot risk assessment 

annually.

Strong for Not Reviewed, 

Amended

21. We recommend referring patients with limb-threatening conditions to the 

appropriate level of care for evaluation and treatment.

Strong for Not Reviewed, 

Amended

22. We recommend a retinal examination (e.g., dilated fundus examination by 

an eye care professional or retinal imaging with interpretation by a 

qualified, experienced reader) be used to detect retinopathy. 

Strong for Not Reviewed, 

Amended

23. We suggest screening for retinopathy at least every other year (biennial 

screening) for patients who have had no retinopathy on all previous 

examinations. More frequent retinal examinations in such patients should 

be considered when risk factors associated with an increased rate of 

progression of retinopathy are present. Patients with existing retinopathy 

should be managed in conjunction with an eye care professional and 

examined at intervals deemed appropriate for the level of retinopathy.

Weak for Not Reviewed, 

Amended

24. We recommend that all females with pre-existing diabetes or personal 

history of diabetes and who are of reproductive potential be provided 

contraceptive options education and education on the benefit of 

optimizing their glycemic control prior to attempting to conceive.

Strong for Not Reviewed, 

Amended

25. We recommend that all females with pre-existing diabetes or personal 

history of diabetes who are planning pregnancy be educated about the 

safest options of diabetes management during the pregnancy and referred 

to a maternal fetal medicine provider (when available) before, or as early 

as possible, once pregnancy is confirmed. 

Strong for Not Reviewed,

Amended

*For additional information, please refer to Grading Recommendations.

†For additional information, please refer to Recommendation Categorization and Appendix F.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 23 of 160

A. General Approach to T2DM Care

Recommendation

1. We recommend shared decision-making to enhance patient knowledge and satisfaction.

(Strong for | Reviewed, New-added)

Discussion

SDM is the process by which the patient and family in conjunction with the provider of care come to an 

agreement about a plan of care and treatment. Key principles include the patient/family readiness, 

provision of benefits and harms of all options in understandable tools, and incorporation of 

preferences.[25,26] SDM includes eight steps: 1) Ask – identify Issues; 2) Prioritize – explore what the 

patient wants; 3) Assess – look for barriers to the SDM; 4) Advise – benefits, risks of patient choice; 5) 

Acknowledge – criteria of the basis for the decision; 6) Assist- explore the options; 7) Make the decision; 

and 8) Evaluate – how did the choice work? Be prepared to review and revisit as needed. Is the patient 

satisfied with the outcome?[25]

Confidence in the quality of evidence was high regarding SDM for improving patients’ knowledge, 

satisfaction and engagement with their treatment plan.[30-32] A prescribed type of approach to SDM is 

not well defined in the literature for individual patient groups and represents a research gap in this area. 

Patient preference must be a consideration. However, the studies utilized for this recommendation 

noted patients may have varying responses to their clinical providers when approached to engage in 

SDM processes. Patients that are diagnosed with DM may respond differently to SDM depending on 

personal goals, life experiences, and coping strategies.[30-32] SDM should not be used just for a patient 

with stable glycemic controls; it should be used to assist those patients that may not be able or willing to 

make those lifestyle changes and decisions that affect their health condition at any time during the 

course of their disease. This should include, at a minimum, diagnosis, difficulties in management, and 

times of transition or development of complications.[32]

Shared understanding is critical to the SDM process. Health coaching and motivational interviewing 

strategies can assist clinicians to understand patients' perceptions, values and beliefs regarding their 

condition, treatment and self-management options, particularly when patients appear to be reluctant to 

fully participate in decisions and care. Studies indicate there may be other approaches that use health 

coaching and motivational interviewing approaches to promote medication compliance/adherence and 

follow through. Using motivational interviewing techniques can make it easier to understand the specific 

level of patients’ perception of the disease process and their comfort level discussing this process. 

Motivational interviewing is one of the techniques that may be used in the process of SDM. It provides a 

communication skill which may be lacking in some patient arenas. When a provider uses motivational 

interviewing skills it may increase the dialogue between provider and patient thus developing a trust 

level more rapidly and more effectively. 

Sharing healthcare decisions requires a healthcare system which supports the process, and patients, 

providers, and healthcare team members who are encouraged to share decisions. The benefits of SDM 

usually outweigh the harms with increase in patient satisfaction and treatment “buy-in” regarding the 

ways and methods to reach that particular goal or treatment plan.[30] When patient preferences are 

considered, it reinforces a trusted therapeutic relationship and creates “good-will” as a shared 

responsibility for patient health outcomes. 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 24 of 160

SDM may be time intensive as the provider has to create an environment of consideration and goal 

formation. Clinical training in these communication skills may be a win as research indicates that 

patients most likely to participate in this SDM process are comfortable speaking with their providers and 

have some level of knowledge of their specific disease process.[33] Our challenge is to help patients 

understand how they can successfully manage DM and partner with their providers and healthcare 

teams to share their goals and preferences to individualize healthcare decisions. Providing system 

supports, SDM tools, and assuring that providers and teams can use patient-centered communication 

skills will increase patients’ willingness to share decisions. These factors are the key to SDM. 

Recommendation

2. We recommend that all patients with diabetes should be offered ongoing individualized 

diabetes self-management education via various modalities tailored to their preferences, 

learning needs and abilities based on available resources.

(Strong for | Reviewed, New-replaced)

Discussion

Diabetes Self-Management Education (DSME) and Diabetes Self-Management Support (DSMS) provide a 

framework involving a collaborative, on-going, interactive process focusing on the patient with DM to 

gain knowledge, modify behavior, and successfully manage the disease. The process requires ongoing 

interactive information-sharing between the diabetes team and the patient.

The goal of diabetes education in SDM is to ensure the patient has sufficient knowledge and skills to 

achieve the treatment goals they agreed upon with their healthcare provider. Participants in the patient 

focus group emphasized the importance of DSME and that understanding diabetes is important for selfmanagement of the disease. A strong message from the focus group was that clinicians need to account 

for the specific circumstances (e.g., cognitive impairment, changing life situations, culture/belief system) 

of each patient, have detailed knowledge about the various treatment options, and plan accordingly for 

each patient.

The reviewed literature acknowledged the value of DSME-DSMS to facilitate patient management, 

improve patient outcomes, as well as reduce overall diabetes-related costs. DSME is differentiated from 

traditional education which is didactic and tends to be delivered in lecture format only.[34] DSME as 

described in the literature is a dynamic process that provides knowledge and self-management skillbuilding activities based on individual needs, attitudes, beliefs, and ever-changing life situations.[34,35]

The content of DSME varied between studies, but the following topics were consistently covered during 

study interventions: knowledge about diabetes and treatment options, medications, nutrition, exercise, 

hypoglycemia, monitoring of glucose and HbA1c, psychosocial and behavioral components, risk 

reduction, foot care, smoking cessation, chronic complications, and sick day management.[35-39]

DSME may be delivered via various modalities, including group sessions/discussion, telephone, webbased technology, multimedia presentations, teach-back, and role play. The reviewed literature 

addressed various modes of delivery and varied in the content of educational materials and time 

allotted for the intervention (varied from 1 to >20 hours), as well as the specific population subgroups 

that were studied. Due to wide variability in the evidence reviewed, the Work Group classified the 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 25 of 160

confidence level for the quality of evidence as low. Most studies favored group DSME over usual care 

(individual visit with primary care provider).[34,36,40] When comparing different modalities of 

providing DSME, the evidence identified positive patient outcomes for DSME delivered in group settings, 

individual settings, or using technology-based systems (e.g., telephone, internet).[38,41,42] Pillay et al. 

concluded that the greater the time spent with the patient was associated with improved outcomes and 

there is a need to provide DSME, DSMS, and/or behavioral programs to assist with lifestyle change.[40]

DSME-DSMS may be provided individually or in a group, based on available resources. Group-based 

DSME-DSMS is cost-effective and provides foundational support for individuals with diabetes to meet 

and discuss common issues.[34,36] Individual education can be time and resource intensive, but should 

be considered especially for individuals with special needs (e.g., cognitive issues, hearing or sight 

impairment). While the evidence did not favor group over individual DSME, individuals with poor 

glycemic management benefitted more from individual interventions than those with good glycemic 

management.[39] A combination of group and individual DSME-DSMS may be effective in providing 

general information and developing personalized goals/treatment plans more efficiently.

Success of DSME in the literature was dependent on program intensity and the delivery personnel or 

format.[34] DSME-DSMS was shown to require substantial contact time and a support component to 

train individuals in self-care skills. Tailoring DSME to ethnic minorities was shown to be beneficial.[35]

Resources to provide DSME will vary greatly and may be limited at some facilities due to inadequate 

staffing or lack of trained personnel. When DSME is not easily available, refer to the network based on 

your organization’s policies. Other options may include community-based programs, web-based 

education, or phone applications.[43]

This Work Group studied one SR,[43] one network meta-analysis,[40] and three RCTs [37,38,44] in an 

effort to evaluate the effectiveness of technology-based DSME programs to aid in guiding this 

recommendation. 

In the SR by Pal et al., technology-based DSME was significantly more effective at six months (-0.2%,

95% CI: -0.4 to -0.1), however, the effect diminished over time and was shown to not be significant 

beyond six months (-0.1%, 95% CI: -0.3 to 0.1).[43] Patients who received technology-based DSME 

reported greater self-efficacy at six to 18 months relative to patients in the control group.

Tang et al. assessed the effectiveness of internet-based DSME in a group of 415 patients with an average 

age of 54 years.[44] Internet-based DSME was associated with greater HbA1c reductions at six months 

(internet-based: Mean Difference [MD] -1.32; usual care [standard-of-care treatment with reminders for 

annual laboratory tests and screenings]: MD -0.66, p <0.001); however, at 12 months follow-up, these 

differences lost statistical significance (internet-based: MD -1.14; usual care: MD -0.95, p=0.133). 

However, treatment satisfaction at 12 months was greatest in patients who received internet-based 

DSME relative to patients who received usual care (p <0.001).[44]

In summary, the reviewed research demonstrated that internet-based DSME is comparable to the 

traditional in-person group DSME class for improvement in HbA1c outcomes.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 26 of 160

The individuals who participated in the patient focus group shared similar and intertwined goals and 

preferences, including maintaining their current work, minimizing treatment side effects, maintaining a 

functional life, and improving QoL. A key suggestion made by the focus group participants was to create 

a formal support system for patients with diabetes such as web-based, online chats, or other types of 

support groups and diabetes education classes to enhance involvement and support.

Incorporation of online learning into the DSME model appears to allow expansion of options for individual 

learners with diabetes who may prefer an online program over an in-person group program. Online 

learning allows the learner to engage in topics of personal interest and reinforce concepts by repeating 

online classes during asynchronous, flexible times. It also allows learners, family members, and co-workers 

the ability to acquire needed information without taking time away from their work schedule.

The literature supports using alternative delivery systems of DSME to provide support and maximize 

learning while presenting core curriculum. The goal of an internet-based strategy is not to replace group 

or individualized DSME programs but to allow adult learners the ability to flexibly engage and invest in 

their diabetes care needs.

DSMS is a recent concept as of this CPG update, and not yet consistently defined or supported in the 

literature. Broadly defined, DSMS is the notion of ongoing support of the individual after receiving 

DSME. While the literature reviewed did not specifically address DSMS, programs that provided ongoing 

support (e.g., periodic follow-up, evaluating and re-establishing goals, support groups) showed better 

outcomes after the initial educational intervention than isolated educational events.[34-36] As stated, 

DSME is a dynamic, on-going process where educational needs will vary and fluctuate with changes to

medication regimens, medical conditions, and life situations.[34,35] Positive patient outcomes, such as 

improved HbA1c levels, increases in physical activity, emotional stability, and decreased BMI typically 

peaked at three to six months; but without ongoing support programs in place, the benefits will likely 

decline.[40,43] This was further validated by the patient focus group who advocated for on-going 

support to enhance self-management. The expectation, then, should be to use SDM to reassess patient 

treatment goals and educational needs. Ideally, this should be conducted at each visit and addressed 

accordingly using education resources available to the medical treatment facility. 

Evidence shows that self-management training is effective, but most reviews called for further research 

by way of well-designed and long-term studies. Computer-based diabetes self-management 

interventions have limited evidence supporting their use and more research is needed for design, 

delivery and effectiveness. There is also a need to identify effective modalities (e.g., internet, satellite) 

to provide education in areas where an educator is not available.

Recommendation

3. We suggest offering one or more types of bidirectional telehealth interventions (typically health 

communication via computer, telephone or other electronic means) involving licensed 

independent practitioners to patients selected by their primary care provider as an adjunct to 

usual patient care.

(Weak for | Reviewed, New-replaced)
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 27 of 160

Discussion

Available telehealth studies were limited and heterogeneous in design and outcome; telehealth had a 

different meaning in each study. Moreover, most studies looked at telehealth as an adjunct to usual 

care. Tildesley et al. conducted a small study in which 46 patients were randomized to an internet-based 

glucose monitoring system (IBGMS) uploaded every two weeks to a secure, commercially available 

website plus conventional care with endocrinology or to conventional care with endocrinology only.[45]

There was a statistically significant decrease in HbA1c for the IBGMS group (adjusted HbA1c difference -

1.3%) compared to the control group (adjusted HbA1c difference -0.1%) for up to six months of followup. However, patients were returned to conventional care after six months and the effect was not 

sustainable at the 12-month mark. Luchsinger et al., the only large study in the evidence base (N=2,169),

evaluated registered nurse (RN) case management telehealth versus usual care in patients aged ≥ 55 

years.[46] The intervention included a home telemedicine unit with a web-enabled computer and 

modem connection to an existing telephone line. Patients in the telehealth intervention had statistically 

significant sustained reductions of HbA1c over five years of follow-up, but the difference in HbA1c 

reduction was not clinically significant (telemedicine: mean 7.09 ± 0.06 versus usual care: mean 7.38 

±0.06; treatment effect: 0.29, 95% CI: 0.12 to 0.46). 

Two other studies involved primary care providers utilizing telehealth. Holbrook et al. (N=511) evaluated a 

web-based diabetes tracker shared between patients and their primary care providers.[47] There was a 

statistically significant improvement in HbA1c, but not in quality of life, in the intervention group 

compared to the control group. Wakefield et al. (N=108) evaluated the effectiveness of short-term 

targeted use of remote data transmission on treatment in patients who had out of range HbA1c 

measurements.[48] Transmitted data was reviewed by the clinic RN and if issues were identified, they 

were shared with the provider. There was no significant difference in changes in HbA1c from baseline to 

six months of follow-up. Pacaud et al. compared three models of education and communication support in 

newly diagnosed patients (N=68): web static (virtual appointments using asynchronous communication) 

versus web interactive (electronic communication and virtual appointments using synchronous and 

asynchronous communication) versus a control group (face-to-face education, both synchronous and 

asynchronous).[49] There were no overall significant differences among the three groups.

The evidence review focused on the comparative effectiveness of telehealth requiring physician 

interaction or supervision versus standard patient management in improving T2DM-related outcomes. 

However, only three of the five studies identified involved physician interaction and the quality of this 

evidence was graded as low. One study evaluated patient education only via telehealth.[49] Another

study, graded as moderate quality, utilized a RN for case management.[46] Based on the evidence, the 

Work Group determined a team approach incorporating all licensed independent providers was

warranted, which is reflected in the recommendation language.

In summary, data on telehealth outcomes were variable from no benefit to some statistically significant,

but clinically insignificant benefits. Yet, no single study showed harm associated with telehealth; 

outcomes were either neutral or a little to moderately beneficial. Confidence in the quality of the 

evidence regarding the effectiveness of diabetes telehealth education and support is limited. 

Improvements were seen in HbA1c when patients had the ability to upload glucose monitoring device 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 28 of 160

data for review by the RN case manager or provider. Dedication of this resource to high-risk elevated 

HbA1c populations may help control outcomes where utilized. 

B. Glycemic Control Targets and Monitoring

Recommendation

4. We recommend setting an HbA1c target range based on absolute risk reduction of significant 

microvascular complications, life expectancy, patient preferences and social determinants of 

health.

(Strong for | Reviewed, New-added)

Discussion

Consensus suggests that, for summarizing evidence, estimates of absolute risk, rather than relative risk

should be consistently provided for both benefits and harms or burdens.[50-52] The scientific basis for 

presumed benefits and harms derives from the absolute differences in achieved mean updated HbA1c 

levels (not a single point in time) between intervention and control groups and meaningful outcomes in 

clinical trials over a time period of many years. 

As a clinical example on how framing of trial results differs, we use the results from the United Kingdom 

Prospective Diabetes Study 33 (UKPDS) which showed that the major benefit of lowering HbA1c from 

7.9% (average) to 7.0% (average) over 10 years for recent onset disease was prevention of advanced 

microvascular complication, predominantly laser photocoagulation (absolute risk reduction [ARR] was 

3.1/100 persons treated for 10 years).[53] The ARR of any microvascular complication was 5.0/100 and 

the number needed to treat was 19.6. The relative risk reduction was a 37% decrease in risk for 

microvascular complications and was continuous and without a threshold.[53,54] However, the ARR for 

each 1% reduction in HbA1c was less at lower levels of initial HbA1c. The microvascular benefit was 

sustained for 10 years after the trial was completed, although the average HbA1c values converged in 

the treatment groups.[55]

There were three major trials conducted in the 2000s that tested the hypothesis that intensive glycemic 

control (target goal of <7%) improved cardiovascular outcomes in patients with T2DM. Action to Control 

Cardiovascular Risk in Diabetes (ACCORD) [56], Veteran Affairs Diabetes Trial (VADT) [57], and Action in 

Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation 

(ADVANCE) [58] trials were conducted to answer the question of the macrovascular benefit of intensive 

control in patients with diabetes of longer duration. 

Over the course of the randomized trial frame of the studies, there was no cardiovascular benefit in 

ADVANCE or VADT and there was increased mortality in ACCORD, leading to early termination of the 

study. After 10 years of follow-up, patients in VADT had 8.6 fewer major cardiovascular events but no 

survival benefit.[57] There was no cardiovascular benefit in the long-term follow-up of subjects in 

ADVANCE.[58] However, a microvascular benefit was observed during the follow-up period. For ADVANCE, 

the in-trial reductions in the risk of end stage renal disease (ESRD) (7 versus 20 events, hazard ratio [HR]: 

0.35, p=0.02) persisted after 9.9 years of overall follow-up (29 versus 53 events, HR: 0.54, p <0.01). These 

effects were greater in earlier-stage CKD (p=0.04) and at lower baseline systolic blood pressure levels 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 29 of 160

(p=0.01). The effects of glucose lowering on the risks of death, cardiovascular death, or major 

cardiovascular events did not differ by levels of kidney function (p >0.26).[58]

These studies have established that the microvascular benefit of intensive control in patients who were 

older than those enrolled in the UKPDS with longer duration of diabetes was less than in the UKPDS 

study. Macrovascular benefits were not observed. These studies establish that intensive control in an 

older population with established disease should not be routinely implemented. 

Three SRs have examined the effect of intensive glycemic control compared to standard/conventional 

glycemic control in managing adults with T2DM and the recommendations in this guideline are 

consistent with the individual RCTs and follow-up studies.[59-61]

Three medications—metformin, empagliflozin, and liraglutide—have demonstrated a medicationspecific benefit on cardiovascular outcomes in patients with T2DM at high risk for cardiovascular 

events.[62-64] However, while each of these medications lower average blood glucose, the mechanism 

remains unknown and the improved cardiovascular outcomes cannot be ascribed to intensive glycemic 

control.

In recommending a target HbA1c goal for an individual patient, the clinician should take into account the 

patient’s diabetes status (e.g., new onset, intermediate duration, long standing), diabetes complications,

and an estimate of the life expectancy of the patient. We recommend that physicians discuss the 

magnitude of expected benefit using principles of ARR or number needed to treat, not relative risk. The 

aforementioned studies can provide an order of magnitude of expected benefit, especially in older 

adults.[53-61] Additionally, comorbid conditions and social determinants of health that could impact 

harms need to be assessed. 

Patient preferences for a target range are dependent upon individual assessments of the risks and 

benefits of tighter glucose control as well as the use of medications to control hyperglycemia and impact 

upon lifestyle. SDM is a key process in setting HbA1c target ranges, as discussed in Recommendation 1.

We recommend a target HbA1c range rather than an all or none HbA1c target value for several reasons:

1) The clinical trials upon which the benefit of glycemic control is based use an updated HbA1c 

value over time; this cannot be generalized to maintaining an HbA1c value less than any single 

level.

2) Additionally, a single HbA1c measurement even from a high quality laboratory has a range 

around it (i.e., coefficient of variation [CV]). In many laboratories, sequential HbA1c values that 

are within 0.5% HbA1c are not significantly different unless the assay CV is less than 3%, ideally 

2%.[65] Comparing HbA1c tests performed in different clinical laboratories introduces another 

source of error, as does use of point-of-care testing, which tends to have higher CV than 

laboratory assays. 

3) There may be racial differences between estimated average glucose (eAG) and HbA1c values in 

patients with T2DM based upon 7-point glucose testing.[66]

4) Disease states that alter red blood cell turnover may falsely raise or lower HbA1c values 

discordant with actual blood glucose levels.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 30 of 160

Recommendation

5. We recommend developing an individualized glycemic management plan, based on the 

provider’s appraisal of the risk-benefit ratio and patient preferences.

(Strong for | Reviewed, Amended)

Discussion

The most effective diabetes treatment plan is individualized to the patient. The benefits and risks of 

therapy are different for each patient, depending upon the individual’s medical, social, psychological 

status, and personal goals and preferences. Understanding the patient’s goals, lifestyle, and preferences 

helps the provider and team work collaboratively with the patient to create a personalized diabetes care 

plan that integrates the patient’s values and preferences into the provider’s assessment of the riskbenefit ratio.[26] Thus, the risks of a proposed therapy are balanced against the potential benefits. The 

partnership between the patient, provider, and healthcare team optimally begins at the time of initial 

diagnosis. The provider and team should stress that although diabetes is a serious condition, the patient 

can successfully manage it with attention to medications, diet, and physical activity. The other important 

part of this initial message is that there are a number of ways that diabetes can be successfully treated 

and that the best treatment plan is one that meets the patient’s needs and preferences so that the 

patient will be more likely to take steps to successfully manage his or her diabetes each day. Patients 

should be encouraged to work with their provider and team to share decision making regarding glycemic 

targets, therapies, and goals of treatment.[31] Given the limited time available for visits, the healthcare 

team can gain useful information to help them tailor the risks and benefits of possible treatment plans 

to the individual patient. 

Given these considerations, the Work Group advocates for an individualized approach based on the 

patient's absolute risk for developing microvascular complications balanced against known comorbidities, 

projected life expectancy, presence or absence of pre-existing microvascular complications, the risk of 

polypharmacy with attendant drug-drug interactions, exposure to medications with limited post-marketing 

experience, the risk of and ability to perceive hypoglycemia, possible benefits to other comorbidities (such 

as beneficial effects on weight or hypertension), and patient preferences.[67]

Recommendation

6. We recommend assessing patient characteristics such as race, ethnicity, chronic kidney disease, 

and non-glycemic factors (e.g., laboratory methodology and assay variability) when interpreting 

HbA1c, fructosamine and other glycemic biomarker results.

(Strong for | Reviewed, New-added)

Discussion

If the provider suspects the HbA1c to be discordant from the patient’s true level of glycemia, the 

provider should collect and interpret actual glucose levels to inform clinical decisions. Many factors 

affect the measurement of HbA1c besides the level of glycemia.[68] Some of these are well established. 

For example, since HbA1c is dependent upon duration of erythrocytes exposure to glucose, conditions 

that alter erythrocyte life span will affect the measured level of HbA1c.[69,70] Iron deficiency anemia, 

which prolongs red cell life and exposes the cell to glucose for a longer period of time, is associated with 

false elevations of HbA1c.[71] In contrast, conditions that reduce red cell life span (e.g., hemolytic 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 31 of 160

anemia) may result in falsely low HbA1c levels. A variety of other conditions may result in alterations in 

HbA1c measurement (e.g., CKD). Hemoglobin variants can result in either falsely elevated or falsely 

lowered HbA1c, depending on the specific assay used.[4,5,72] In addition, oral hypoglycemic agents 

(metformin or sulfonylureas) may alter the relationship between blood glucose levels and HbA1c, 

although the clinical significance is unclear.[73] There are racial/ethnic differences in HbA1c levels for a 

given level of glycemia. African Americans have, on average, about 0.4% higher HbA1c levels than 

Whites and this difference cannot be explained by measured differences in glycemia or 

sociodemographic factors, clinical factors, access to care, or quality of care. 

Racial differences were reported among participants in the Diabetes Prevention Program. Despite 

having comparable measures of glycemia, African Americans had significantly higher HbA1c levels 

(6.2%) than Whites (5.8%).[6]

Racial differences have also been reported in patients with longer duration of diabetes. In the A 

Diabetes Outcome Progression Trial (ADOPT), baseline HbA1c levels adjusted for age, sex, and BMI were 

0.7% higher in African Americans (8.0% ± 1.1) than Whites (7.3% ± 0.8) despite comparable fasting 

glucose levels (153 mg/dL versus 151 mg/dL).[74] 

Whether these differences are of sufficient magnitude to alter therapy (e.g., use different HbA1c target 

levels depending upon race), is still a matter of controversy.[75,76] Further research is required to 

determine if racial/ethnic differences in HbA1c vary depending on the level of glycemic control, its 

clinical significance, and most importantly, implications for therapy. In light of this, the VA/DoD DM CPG

continues to recommend that a new diagnosis of diabetes be based upon a confirmatory fasting blood 

glucose level ≥126 mg/dL if the initial HbA1c value is between 6.5% and 6.9%.

How and where the HbA1c level is measured can also affect the result because of intra-laboratory 

variation (the variation in test accuracy and precision) and inter-laboratory variation (variation related to 

using different methodologies for the tests themselves). The National Glycohemoglobin Standardization 

Program (NGSP) not only establishes standards but also reports on intra-laboratory variation, typically 

expressed as CV. Of particular note is that point-of-care measurements of HbA1c (e.g., fingerstick HbA1c 

tests) tend to have higher levels of CV, indicating that they may produce less accurate results. An 

analytical CV ≤2% will produce a 95% probability that a difference of ≥0.5% HbA1c between successive 

patient samples is due to a significant change in glycemic control (when HbA1c is 7% [53 

mmol/mol]).[65] Therefore, using HbA1c for diagnosis and treatment requires a highly accurate 

methodology of a degree not required by regulation and that may vary among laboratories.

Consequently, providers and patients need to be aware that HbA1c results can differ based upon 

laboratory factors as well as clinical factors.

Assessing the impact of these patient characteristics and non-glycemic factors that affect HbA1c levels 

allows for better individualization of management. For example, treatment decisions based upon HbA1c 

alone without consideration for glucose monitoring may result in unnecessary initiation or 

intensification of therapy. Thus, we recommend that treatment goals involve target ranges for HbA1c 

rather than levels above or below a specific target value for most persons with diabetes. This approach 

may avoid unnecessary intensification of medication due to random fluctuations within the range 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 32 of 160

related to laboratory variation. This recommendation allows for individualized treatment plans and is 

consistent with patient values. 

Data on other markers are lacking and continuous glucose monitoring is out of the scope of this CPG.

Recommendations

7. We recommend an individualized target range for HbA1c taking into account individual 

preferences, presence or absence of microvascular complications, and presence or severity of 

comorbid conditions (See Table 2).

(Strong for | Reviewed, New-replaced)

8. We suggest a target HbA1c range of 6.0-7.0% for patients with a life expectancy greater than 10-

15 years and absent or mild microvascular complications, if it can be safely achieved (See Table 2).

(Weak for | Reviewed, New-replaced)

9. We recommend that in patients with type 2 diabetes, a range of HbA1c 7.0-8.5% is appropriate 

for most individuals with established microvascular or macrovascular disease, comorbid 

conditions, or 5-10 years life expectancy, if it can be safely achieved (See Table 2).

(Strong for | Reviewed, New-added)

10. We suggest a target HbA1c range of 8.0-9.0% for patients with type 2 diabetes with life 

expectancy <5 years, significant comorbid conditions, advanced complications of diabetes, or 

difficulties in self-management attributable to e.g., mental status, disability or other factors such 

as food insecurity and insufficient social support. (See Table 2).

(Weak for | Reviewed, New-replaced)

Discussion

A substantial body of evidence demonstrates a direct relationship between glucose control and 

microvascular complications (e.g., retinopathy, neuropathy, nephropathy). Higher levels of HbA1c carry 

greater risk of complications and lowering HbA1c prospectively reduces risk.[53,64,77] The relationship 

between HbA1c and the risk of microvascular complications is continuous, and may accelerate with 

HbA1c levels >9%.[78] There is no apparent threshold above which benefits are not accrued by lowering 

HbA1c. However, in contrast to the relative risk of reduction of microvascular complications, which 

remains constant across HbA1c levels, the ARR is less at lower levels of mean achieved HbA1c than at 

higher levels.[54] Conversely, there are no data on the lower limit for achieved HbA1c, albeit there are 

strong data on the risks of hypoglycemia, as HbA1c is targeted to near normal levels for patients 

receiving insulin.[59] Lower levels of HbA1c (closer to 6%) may be reasonable in patients treated with 

metformin alone. 

Microvascular complications develop over an extended period of time. Thus, the subset of individuals 

with longer life expectancy and absent or mild microvascular complications (e.g., early background 

retinopathy, microalbuminuria, mild neuropathy) are most likely to benefit from tight HbA1c control 

(i.e., 6.0-7.0%), see Table 2. 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 33 of 160

Diabetes also confers substantial risk of CVD, but there is no evidence that lowering HbA1c to <8.5% 

reduces mortality, although it reduces the risk of non-fatal myocardial infarction (MI).[79] Indeed, in 

clinical trials of patients treated to HbA1c levels <7% [79-81], not only was there no benefit on CVD risk 

but one trial showed increased mortality during the course of the RCT.[80] Consistent with these 

findings, three SRs comparing intensive and conventional glucose control showed no significant 

differences in all-cause mortality or death from CVD, but did demonstrate significant risk reduction for 

microvascular complications such as nephropathy, retinopathy, and lower extremity amputation.[59-61]

In some circumstances, aggressive glucose management may cause harms due to medication therapy. 

This is particularly true for patients with T2DM treated with insulin. Intensive glucose control 

significantly increases the risk of severe hypoglycemia (e.g., requiring help from another person) by twofold when compared to conventional control. Follow-up of ACCORD study patients for a median of 8.8 

years showed a significant 20% increased relative risk of death from cardiovascular events with intensive

glycemic control, but the absolute risk difference of 0.13% per year was minimal, compared to standard,

glycemic control.[82] Intensive control is also associated with increased weight gain.[81] It remains 

unknown if the risk/benefit ratio for intensive glucose control will differ with newer medications and/or 

extend to include macrovascular benefits. However, the FDA does provide clinical alerts regarding 

complications of individual or classes of medications for complications including osteoporosis, 

congestive heart failure, urinary tract infections, dehydration, and acute kidney injury, among others. 

The risk of complications may be exacerbated by underlying comorbid conditions.

Safely achieving intensive control requires attention to the risk factors for hypoglycemia. In addition to 

the higher risk of hypoglycemia with specific drugs (insulin and sulfonylureas), factors associated with 

risk of hypoglycemia include advanced age (especially >75 years), cognitive impairment, and chronic

renal insufficiency (including causes unrelated to diabetic nephropathy).[83-85] Additional factors 

associated with hypoglycemia risk include lack of appropriate glucose monitoring, inadequate diabetes 

education, lack of family and social support systems, and food insufficiency. As a result of these factors, 

some patients may have life expectancies exceeding 10 years, yet be considered for less intensive 

glycemic control. 

The results of recent trials of intensive glycemic control evaluating cardiovascular outcomes can help to 

inform the target HbA1c range of a patient population that is unlikely to benefit from intensive control 

(HbA1c 6.0-7.0%). Three major intensive control studies were designed to evaluate cardiovascular 

outcomes (ACCORD [56], VADT [57], and ADVANCE [58]), but varied somewhat in study populations, 

definition of intensive control, and intervention strategies. Nonetheless, the overall results did not show 

a reduction in macrovascular disease outcomes with intensive glucose control, while it did show a 

significantly increased risk of hypoglycemia. The target HbA1c in the standard control arm in ACCORD 

was 7.0-7.9%, in ADVANCE the achieved HbA1c was 7.3%, and in VADT the achieved HbA1c in the 

standard control group averaged 8.4%. By considering the severity of diabetes complications, comorbid 

conditions, and estimation of life expectancy, clinicians can recommend a glycemic target range to be 

discussed with the individual patient. This is especially important for patients who would not have been 

candidates for the RCT because of decreased life expectancy, significant comorbid conditions, and social 

determinants of health that place them at greater risk for adverse events from medication therapy.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 34 of 160

Newer therapeutic options have been introduced since these major trials were completed, and further 

research is needed to understand which populations may benefit from the effects of newer therapies on 

macrovascular disease outcomes and/or lower HbA1c targets.

In summary, the reviewed evidence supports a clinically significant benefit from intensive glycemic 

control (HbA1c 6.0-7.0%) in individuals with longer life expectancy, short duration of diabetes, and 

absent or mild microvascular complications. Life expectancy estimates are not always reliable, but can 

be estimated based on information discussed between patients and providers such as functional status, 

history of multiple recent hospitalizations, organ failure (advanced renal disease, liver disease, or heart 

failure), cancer diagnoses and their treatment plans, and advanced medical directives. For most patients 

with established microvascular or macrovascular disease, comorbid conditions, or less than 10 years life 

expectancy, it is reasonable to achieve a target HbA1c between 7.0-8.5%, after discussion of the risks 

and benefits, see Table 2. For patients with a life expectancy <5 years, the upper limit of HbA1c should 

reflect the need to avoid symptoms of hyperglycemia. As discussed in Recommendation 6, HbA1c is 

influenced by many factors, including age, race/ethnicity and anemia/hemoglobinopathies. In 

considering upper target levels, especially for individuals with comorbid conditions and limited life 

expectancy, the Work Group balanced benefit, safety, and preferences, and set that level at 9.0%. 

Preferably, decisions on intensification of therapy should be based on glucose levels and not HbA1c 

values. Additionally, there should be consideration of hyperglycemic and hypoglycemic symptoms, and 

patient preferences, especially regarding initiation or change in insulin dosage. The overarching purpose 

of these four recommendations is to move away from a one-size-fits-all approach, to individualized 

treatment plans and HbA1c target range that are tailored to a patient’s unique characteristics and goals 

of care. The target range should be reviewed at least annually, or as a result of a request by the patient 

or healthcare team, or as a result of changes in the patient's medical status.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 35 of 160

Table 2: Determination of average target HbA1c level over time 1,2,3,4,5,12

Major Comorbidity6 or 

Physiologic Age

Microvascular Complications

Absent or Mild 7 Moderate 8 Advanced 9

Absent*

> 10-15 years of life

expectancy

6.0-7.0%† 7.0-8.0% 7.5-8.5%‡

Present 10

5-10 years of life expectancy 7.0-8.0%† 7.5-8.5% 7.5-8.5%‡

Marked 11

<5 years of life expectancy 8.0-9.0%‡ 8.0-9.0%‡ 8.0-9.0%‡

*Progression to major complications of diabetes is likely to occur in individuals with longer than 15-20 years of life expectancy.

Therefore, goal ranges are more beneficial early in disease in younger individuals, or healthier older adults with a longer life 

expectancy.

†Without significant side effects, including but not limited to hypoglycemia.

‡Further reductions may be appropriate, balancing safety and tolerability of therapy. 

HbA1c laboratory considerations:

1 Based upon the NGSP reference standard. Clinicians need to obtain information regarding the CV from the methodology used at 

their site. As an example, an HbA1c of 8.0% from a laboratory with a CV of 3% would be within a 7.76-8.24% range 13 out of 20 

times (1 standard deviation), and would be between a 7.53-8.47% range 19 out of 20 times (2 standard deviations).

2 The HbA1c range reflects an “HbA1c average goal” over time. Intensification or relaxation of therapy should be undertaken

based upon individual clinical circumstances and treatment options. 

3 A medication change in response to a single HbA1c test that encompasses the "goal" is discouraged, especially if it is 

discordant with self-monitoring of blood glucose (SMBG) results. 

4 African Americans, on average, have higher HbA1c levels than Whites and this difference cannot be explained by measured 

differences in glycemia. Caution is recommended in changing medication therapy based upon HbA1c results, especially for 

patients on insulin therapy, without correlation with SMBG results.

5 For all of the above reasons, the VA/DoD DM CPG does not recommend the use of estimated average glucose.

Comorbid illness considerations: 

6 Major comorbidity includes, but is not limited to, any or several of the following active conditions: significant CVD, severe CKD, 

severe COPD, severe chronic liver disease, recent stroke, and life-threatening malignancy.

7 Mild microvascular disease is defined by early background retinopathy, and/or microalbuminuria, and/or mild neuropathy.

8 Moderate microvascular disease is defined by pre-proliferative (without severe hemorrhage, intra-retinal microvascular 

anomalies [IRMA], or venous bleeding) retinopathy or persistent, fixed proteinuria (macroalbuminuria), and/or demonstrable 

peripheral neuropathy (sensory loss).

9 Advanced microvascular disease is defined by severe non-proliferative (with severe hemorrhage, IRMA, or venous bleeding), 

or proliferative retinopathy and/or renal insufficiency (serum creatinine level > 2.0 mg/dL), and/or insensate extremities or

autonomic neuropathy (e.g., gastroparesis, impaired sweating, orthostatic hypotension).

10 Major comorbidity is present, but is not end-stage and management is achievable.

11 Major comorbidity is present and is either end-stage or management is significantly challenging. This can include mental 

health conditions and substance/opioid use.

Social determinant considerations:

12 Social determinants of health, including social support, ability to self-monitor on insulin, food insufficiency, and cognitive 

impairment need to be considered. Additionally, side effects of medications and patient preferences need to be considered in 

a process of shared decision-making.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 36 of 160

Recommendation 

11. We suggest that providers be aware that HbA1c variability is a risk factor for microvascular and

macrovascular outcomes.

(Weak for | Reviewed, New-added)

Discussion

HbA1c variability refers to variation in glycemic control over the long-term as assessed by measurement 

of HbA1c, not the day-to-day variation in blood glucose levels. A variety of measures of HbA1c variability 

were used including the standard deviation (SD) (how much values differ from the group mean) and also 

as a CV (the ratio of SD to the mean). 

An SR of 13 studies found consistent associations between HbA1c variability and micro- and 

macrovascular complications and mortality in T1DM and T2DM.[86] The association was greatest with 

mortality. However, the quality of evidence was low because of high risk of bias due to concerns

regarding the small number of studies for analyses, the observational nature of the studies, 

retrospective design of some studies, unclear or short follow-up periods, and lack of adjustment for 

some potential confounders. Notably, the number of HbA1c measurements per patient ranged from 

three to a median of 79 and follow-up periods were similarly variable. More recently, a retrospective 

study involving Veterans (N >50,000) showed a similar association with mortality as well as MI and 

stroke over a mean period of 3.3 years.[87] 

Although HbA1c variability is an independent predictor of adverse health outcomes compared to mean 

HbA1c alone, there is insufficient information to make any statement about a causal effect of HbA1c

variability on these outcomes. Thus, it is unknown whether reducing HbA1c variability will have 

beneficial or adverse effects. Further research is necessary to assess whether HbA1c variability would be 

useful clinically for risk stratification and whether it might be a valuable therapeutic target. 

The benefits of assessment of HbA1c variability outweigh the harms, and data from the patient focus 

group and elsewhere indicate that there is an interest among patients to have more information about 

DM management and optimal treatment. There are implications for resource use and feasibility related 

to the effort required to obtain the necessary data to calculate the degree of variability. There may be 

particular implications for DoD due to changes related to deployment (operations tempo [OPTEMPO]). 

Further research is required to determine the best measures of HbA1c variability and practical means to 

communicate them, whether or not there is a dose-response relationship of magnitude of variability or 

exposure to variability, and most importantly whether interventions to reduce HbA1c variability affects 

outcomes.

C. Non-pharmacological Treatments

Recommendation

12. We recommend offering therapeutic lifestyle changes counseling that includes nutrition,

physical activity, cessation of smoking and excessive use of alcohol, and weight control to

patients with diabetes (See VA/DoD CPGs for obesity, substance use disorders, and tobacco

use cessation).

(Strong for | Not Reviewed, Amended)
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 37 of 160

Discussion

All patients with diabetes should be given lifestyle counseling. Lifestyle changes counseling is indicated 

for all diabetes patients and should include nutrition guidance, physical activity, cessation of smoking 

and excessive use of alcohol, and weight control.[88-91] Based on the VA/DoD Obesity CPG, the 

definition of comprehensive lifestyle intervention is, "interventions that combine three critical lifestyle 

components (i.e., dietary, physical activity and behavioral components) and include at least 12 

intervention sessions over a 12-month period (See Recommendations 7, 10, 18, 23, 24, 31 and Appendix 

G in the VA/DoD Obesity CPG9

).

The confidence in the quality of evidence for this recommendation is moderate and the benefits of 

therapeutic lifestyle changes counseling outweigh the harms/burden of implementing it. Among the 

included studies in the Ajala et al. SR, three of the diets were compared to standard or control diet (high 

protein diet versus standard protein diet, lower carbohydrate diet versus control diet, and 

Mediterranean diet versus control diet); the others compared one diet to a different diet (American 

Diabetes Association [ADA] diet versus ADA plus peanuts diet, Atkins diet versus ADA diet, high-protein 

diet versus low protein diet, lower carbohydrate diet versus control diet, low fat diet versus low 

glycemic load diet, Mediterranean diet versus control diet, vegan and vegetarian diets versus 

conventional diabetes diet). Only two of the diets were effective in weight management.[92] A referral 

to a dietitian to support dietary changes should occur.[93] There are benefits beyond glycemic control. 

The only harm identified is a potential increased risk of injury with physical activity. A patient’s 

preferences and current level of health and comorbidities will vary and therefore must be taken into 

consideration.

The medical nutrition therapy (MNT) process consists of distinct, interrelated steps:

• Nutrition Assessment: The registered dietitian nutritionist (RDN) collects and documents 

information such as food or nutrition-related history; biochemical data, medical tests and 

procedures; anthropometric measurements, nutrition-focused physical findings and client 

history.

• Diagnosis: Data collected during the nutrition assessment guides the RDN in selection of the 

appropriate nutrition diagnosis.

• Intervention: The RDN then selects the nutrition intervention that will be directed to the 

etiology of the nutrition problem and aimed at alleviating the signs and symptoms of the 

diagnosis.

• Monitoring/Evaluation: The final step of the process is monitoring and evaluation, which the 

RDN uses to determine if the patient/client has achieved, or is making progress toward, the 

planned goals.

Resource considerations include the cost of diabetic nurse educators, RDNs, and behaviorists. It is also 

expensive, inconvenient, and time consuming for patients to adhere to therapeutic lifestyle changes. 

Resource availability to achieve goals varies (e.g., access to a smoking cessation class). Other factors, such 

 9 See the VA/DoD Clinical Practice Guideline for Screening and Management of Overweight and Obesity. Available at: 

http://www.healthquality.va.gov/guidelines/CD/obesity/
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 38 of 160

as socioeconomic issues (especially food insecurity), conflicts with the patient’s preference and culture, 

and impact on family members must also be taken into consideration. 

For the management of obesity, in particular bariatric surgery, see the VA/DoD Obesity CPG.

10 For smoking 

cessation and alcohol use, see the VA/DoD CPG for Treating Tobacco Use and Dependence and the 

VA/DoD SUD CPG.

11,12 

Further research studies are required to address sustainability over the long-term (greater than five 

years). Research is also needed on effective methods to implement the interventions.

Recommendation 

13. We recommend a Mediterranean diet if aligned to patient’s values and preferences.

(Strong for | Reviewed, New-added)

Discussion

The ideal distribution of the three main food components, carbohydrates, proteins and fats, remains 

unclear. Dietary recommendations for improving glycemic outcomes often have focused on individual 

macronutrients, specifically carbohydrate reduction. Although carbohydrate reduction is well 

researched as a strategy for glycemic control, recent studies have focused on overall dietary patterns 

and the link to chronic disease control, prevention, and treatment. As such, a Mediterranean-style 

dietary pattern has been shown to be effective in improving glycemic control, delaying the time to first 

pharmacological intervention, in addition to reducing cardiovascular risk factors and weight in 

individuals with T2DM.[92] 

Despite known variation in the cuisine of Mediterranean countries, certain characteristic features are 

commonly used to describe a traditional Mediterranean diet: high intake of vegetables, fruits, nuts, 

unrefined grains, and olive oil; moderate intake of fish and poultry; low or moderate intake of wine; and 

low intake of red meat, processed meat, dairy, and sweets. 

In a meta-analysis of nine RCTs, Huo et al. found that a Mediterranean diet significantly reduced HbA1c 

and fasting glucose levels in patients with T2DM.[94] A similar SR by Esposito et al. found a 0.47% 

reduction in HbA1c favoring a Mediterranean diet compared to usual care or a low-fat diet.[95] 

A Mediterranean diet has also been linked to improved cardiovascular outcomes and weight loss. Huo et 

al. found a significant reduction in total cholesterol and triglyceride levels and increased HDL-C in those 

following a Mediterranean diet along with an average of weight loss of 0.29 kg.[94] 

Only three of the reviewed studies were based on the U.S. population and the availability of foods 

commonly consumed as part of a Mediterranean diet may be perceived as difficult or challenging for 

10 See the VA/DoD Clinical Practice Guideline for Screening and Management of Overweight and Obesity. Available at:

http://www.healthquality.va.gov/guidelines/CD/obesity/

11 See the VA/DoD Clinical Practice Guideline for Treating Tobacco Use and Dependence. Available at:

http://www.healthquality.va.gov/guidelines/CD/mtu/ 

12 See the VA/DoD Clinical Practice Guideline for the Management of Substance Use Disorders (SUD). Available at: 

http://www.healthquality.va.gov/guidelines/MH/sud/
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 39 of 160

individuals in the VA/DoD population. To improve compliance, MNT should be aligned with the patients’ 

values and preferences and focused on attainable and sustainable dietary modifications. 

Although a Mediterranean diet has shown to improve glycemic control, weight, and cardiovascular 

outcomes in patients with T2DM more research is needed evaluating the effects and availability of the 

diet in the U.S. population, particularly in the VA and DoD.

Recommendation

14. We recommend a nutrition intervention strategy reducing percent of energy from carbohydrate 

to 14-45% per day and/or foods with lower glycemic index in patients with type 2 diabetes who 

do not choose the Mediterranean diet.

(Strong for | Reviewed, New-added)

Discussion

A variety of dietary interventions have been shown to be effective for reducing HbA1c and other risk 

factors associated with complications of T2DM. There is increasing evidence that a lower carbohydrate 

diet improves glycemic control and leads to reduction in diabetes medication.[93,96] A lower

carbohydrate diet was shown to achieve a greater reduction in triglycerides and increases in HDL-C in 

some studies suggesting the lower carbohydrate diet may be effective in reducing cardiovascular risk in 

patients with T2DM.[96]

While the bodies of evidence for Mediterranean diet and lower carbohydrate dietary approaches 

showed their effectiveness in patients with T2DM, the evidence in support of the Mediterranean diet 

was more uniform and robust than that for the lower carbohydrate dietary approaches. Therefore, we 

recommend the Mediterranean diet be offered first to patients. However, depending on patients’ values 

and preferences, those who do not prefer the Mediterranean diet are offered lower carbohydrate 

dietary approaches.

During the VA/DoD Work Group analysis of multiple nutrition intervention strategies evaluating variable 

percentage of kilocalories (kcals) from carbohydrate, it was clear to the Work Group that in every study 

meeting GRADE requirements, the nutrition intervention strategy with a lower percent of energy coming 

from carbohydrate resulted in improved clinical surrogate markers. These markers included, but were not 

limited to HbA1c, self-monitoring of blood glucose (SMBG) values, post-prandial blood glucose, weight, 

reduction in pharmacological agent requirements, improved lipids, and improved blood pressure. While 

the Work Group is aware of the differences between the Academy of Nutrition and Dietetics’ (AND) and 

our recommendations, our approach was based on our recent SR of the literature and considerations 

specific to the VA/DoD populations.

An SR of 20 RCTs compared dietary interventions including lower carbohydrate and low glycemic index 

diets.[92] Evidence showed both dietary interventions improved glycemic control. The majority of the 

lower carbohydrate diets reviewed comprised between 14-45% of energy from carbohydrate and 25-

28% from protein. Another study, an RCT by Fabricatore et al., demonstrated that a Calorie-restricted, 

low glycemic index diet reduced HbA1c and promoted weight loss.[97]Improvement of glycemic control 

is independent of weight loss with lower carbohydrate diets. Low glycemic index diets provide patients 

with another alternative. 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 40 of 160

In a 16-week trial, Yancy et al. showed that a low carbohydrate, ketogenic diet resulted in improved 

glycemic control and discontinued or reduced diabetes medication for most participants.[98] It was 

noted in this study that patients using a low carbohydrate ketogenic diet should be under close medical 

supervision or be capable of self-adjusting medication. Evidence for a very low carbohydrate ketogenic 

diet is increasing both for T2DM and weight loss. Lower carbohydrate diets, especially those containing 

less than 70 grams carbohydrate per day, should be planned carefully to assure proper nutrition with 

the assistance of a dietitian. 

Protein and fat replaces carbohydrate in a lower carbohydrate diet, which raises concern that increased 

dietary protein could cause deterioration in renal function in patients with advanced renal disease. 

Pedersen et al. compared a high protein diet to a standard protein diet which showed no evidence that 

increased protein intake (90-120 grams protein per day, 30% of energy from protein) had any adverse 

effect on renal function in patients with mild renal impairment (estimated glomerular filtration rate 

[eGFR] >40 mL/min/1.73 m2

).[99] 

This recommendation allows for meal planning options to account for patient preferences. The patient 

focus group expressed the desire for providers to take into consideration patient treatment preferences. 

Utilizing SDM may benefit patients when initiating a dietary intervention. We suggest dietary education 

and behavioral counseling be facilitated by a RDN.[91] Studies show improved glycemic control and weight 

loss when intensive behavioral counseling and increased physical activity are combined with dietary 

interventions (see the VA/DoD Obesity CPG13).[93,96] There is no consensus on the definition of a low 

carbohydrate diet. Dietitians can offer lower carbohydrate options specifically tailored to the patient’s 

needs, ensuring nutritional adequacy, and work with providers for timely adjustments of diabetes 

medications. For patients following a lower carbohydrate diet and who are taking hypoglycemia agents, 

management by an interdisciplinary team, including a dietitian, is recommended. 

The quality of the evidence reviewed for this recommendation was low due to wide definition of 

components, imprecision, and limited duration and follow-up. Dietary intervention studies tend to 

compare diet versus diet rather than comparing diet versus control. 

Carbohydrate reduction and low glycemic index are suggested dietary options in which the benefits 

outweigh harms. Adherence to these dietary interventions may be expensive, inconvenient, and time 

consuming for patients with T2DM. Family member preferences affect the level of success of dietary 

interventions. A referral to a RDN may facilitate patient education and promote a more effective dietary 

intervention. These guidelines do not completely address the role of protein as a macronutrient in 

patients with mild renal disease.[99] However, the progression of advanced CKD (Stage 3-4) might be 

delayed by protein restriction of 0.6-0.8 g/kg/d (see the VA/DoD Clinical Practice Guideline for the 

Management of Chronic Kidney Disease in Primary Care [VA/DoD CKD CPG]14). 

13 See the VA/DoD Clinical Practice Guideline for Screening and Management of Overweight and Obesity. Available at: 

http://www.healthquality.va.gov/guidelines/CD/obesity/

14 See the VA/DoD Clinical Practice Guideline for the Management of Chronic Kidney Disease in Primary Care. Available at: 

http://www.healthquality.va.gov/guidelines/CD/ckd/
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 41 of 160

The VA/DoD population presents unique challenges of feasibility and acceptability of diet and lifestyle 

changes. Further research to determine new strategies that maximize adherence is needed for this 

population. Future research is needed to study the long-term effects of dietary modifications and 

specifically the implementation of a low glycemic index diet outside of the research setting. We did not 

address MNT in conjunction with pharmacotherapy because of lack of evidence. Research comparing 

initiating nutrition therapy as a first-line therapy versus pharmacotherapy is needed.

D. Inpatient Care

Recommendation

15. We recommend against targeting blood glucose levels <110 mg/dL for all hospitalized patients 

with type 2 diabetes receiving insulin.

(Strong against | Reviewed, Amended)

Discussion

Hyperglycemia during hospitalization is associated with adverse outcomes independent of diabetes. 

Importantly, glucose lowering interventions have been shown to reduce morbidity and mortality in 

some critically ill populations. Most of the controversies in this setting have centered on the ideal and 

exact glucose target for hospitalized patients, as well as which populations would derive benefit from 

glucose lowering interventions. Evidence to support “tight” glycemic control (80-110 mg/dL) remains 

insufficient. Randomized trials examining glycemic control and/or insulin therapy are limited to the 

study of hospitalized patients with severe illness (e.g., intensive care unit [ICU], acute myocardial 

infarction (AMI), acute stroke). In the Normoglycemia in Intensive Care Evaluation-Survival Using 

Glucose Algorithm Regulation (NICE-SUGAR) study, a blood glucose target of 180 mg/dL or less resulted 

in lower mortality (odds ratio [OR]=1.14) than did a target of 80 to 110 mg/dL in which hypoglycemia 

was more frequent (OR=14.7).[100] This data is often extrapolated to the inpatient setting at large, 

though there have been no controlled trials conducted in other settings evaluating “tight” control 

outcomes.

The Efficacy of Volume Substitution and Insulin Therapy in Severe Sepsis (VISEP) trial was a four-arm 

study examining both fluid resuscitation and “tight” glycemic control (80-110 mg/dL) in ICU patients 

with severe sepsis.[101] The trial was stopped early due to high rates of hypoglycemia (17% versus 4%).

It is important to note that only 30% of the studied patients had a prior diabetes diagnosis; presumably,

hyperglycemia in the remainder of the patients was of a different process (e.g., stress hyperglycemia of

critical illness), though the results seem to suggest that targeting lower glucose levels with insulin in the 

ICU can result in concerning rates of hypoglycemia. 

Hypoglycemia is the most common complication associated with aggressive inpatient glycemic control, 

and is one of the leading adverse outcomes limiting the quality of trials addressing the benefits of 

intensive glycemic control.[100,102,103] In a meta-analysis by Griesdale et al., among the trials that 

reported hypoglycemia, the pooled relative risk with intensive insulin therapy was 6.0 (95% CI: 4.5 to 

8.0).[104] Severe and multiple hypoglycemic episodes are associated with increased risk of death in ICU 

patients.[105]
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 42 of 160

While lower glucose levels might physiologically result in benefit, it can be logistically challenging to 

achieve them without risking hypoglycemia. In recent publications on the topic and in common 

clinical practice there is a greater appreciation of risk of harms from hypoglycemia. For these reasons 

and due to evidence suggesting harm with lower glucose levels, the Work Group strongly 

recommends 110 mg/dL as the lower limit for inpatient control. Advancement in glucose monitoring 

technologies, such as continuous glucose monitors (CGM), may improve the capability to safely target 

lower glucose levels; however, performance of these devices in acutely ill hospitalized patients is not 

well studied.

Recommendation

16. We recommend insulin be adjusted to maintain a blood glucose level between 110 and 180 

mg/dL for patients with type 2 diabetes in critically ill patients or those with acute myocardial 

infarction.

(Strong for | Reviewed, Amended)

Discussion

Many of the trials examining insulin therapy in the hospital have specifically studied glucose-insulinpotassium (GIK) infusions with little or no regard to the glucose level or treatment of hyperglycemia. 

This is particularly evident in studies of patients with AMI. SRs have generally found that GIK 

interventions do not improve outcomes especially if glucose lowering is not a goal.[103,106-108]

Moderate levels of glycemic control have not been well studied. One of the earliest randomized trials of 

insulin therapy after AMI that predates more rigorous standards, the Diabetes Mellitus Insulin-Glucose 

Infusion in Acute Myocardial Infarction (DIGAMI) trial, was able to demonstrate reduced mortality rates 

with glucose lowering <180 mg/dL.[109] Among the patients with admission blood glucose levels ≥200 

mg/dL who received the glucose-lowering intervention, mortality at one year decreased by 29%. A 58% 

relative reduction in hospital mortality in the intervention group was observed for the pre-defined subgroup of patients who were insulin naïve and low cardiovascular risk, but not for the intent-to-treat 

group. Nevertheless, since the intervention arm of DIGAMI included three months of intensive insulin 

therapy after discharge, it was not possible to discern whether the reduction in long-term morbidity and 

mortality was due to inpatient treatment, outpatient treatment, or the combination. DIGAMI-2 was 

designed to resolve this issue, but was not successful in achieving this primary goal due to insufficient 

power, and again, the inability to reach treatment goals.[110]

As standards of care have improved over the years, it has become increasingly difficult to design a study 

in which the control group is sufficiently more hyperglycemic than the intervention group to 

demonstrate a difference in outcome. The mean glucose at 24 hours of the control group in the DIGAMI1 study was 211 mg/dL.[109] In contrast, the mean glucose of the control group in the recent NICESUGAR trial was 144 mg/dL. This has several implications. First, trials such as NICE-SUGAR are examining 

the effects of “tight” glycemic control versus “good” glycemic control, not poor glycemic control, and 

therefore the absence of treatment benefit observed cannot be used to justify hyperglycemia in the 

hospital setting. Second, a narrower gap between glucose levels in both groups requires a larger sample 

size, such as that of NICE-SUGAR, to have sufficient power to observe a significant benefit. 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 43 of 160

Other important differences among inpatient insulin therapy trials include variable glucose targets and 

unknown glycemic variability. For instance, a mean glucose of 140 mg/dL in one trial may represent an 

average of many hypoglycemic and hyperglycemic episodes which may have markedly different effects 

on outcomes than what is observed in another trial where mean glucose is 140 mg/dL with little SD. 

Such information is not provided by most trials and this lack of information also limits the interpretation 

of SRs that cannot account for these differences. Similarly, there are differences in protocols among 

trials. This includes frequency and method of glucose measurement. Trials where glucose is measured 

infrequently may underestimate the rate of hypoglycemia which could significantly impact outcomes. 

Furthermore, it has been demonstrated that point-of-care testing, although the most practical method, 

is often inaccurate in critically ill patients.

Lastly, it is important to note that while much of the controversy and attention has focused on the ideal 

glucose target, there are many ways in which the care of hospitalized individuals with diabetes and 

hyperglycemia can be improved. There is a growing body of literature examining the types and methods 

by which antidiabetic agents are applied in the hospital.[111-114] While the methods to achieve 

glycemic target were not systematically reviewed as part of the literature review, we note that in the 

studies reviewed, patients in the ICU were often treated with an insulin drip if their glycemia was above 

180 mg/dL.

Glucose target considerations:

• In order to identify potentially harmful hyperglycemia and hypoglycemia, blood glucose 

monitoring may be ordered in hospitalized patients with diagnosed DM and/or hyperglycemia 

(blood glucose >180 mg/dL) on admission. There is no evidence to support a given frequency of 

monitoring. Therefore, the frequency of monitoring should be based upon clinical judgment 

taking into account the management of diabetes, the reason for admission, and the stability of 

the patient.

• Treatment goals should be periodically reassessed based upon patient specific factors, including 

changes in the patient’s health status, adverse drug reactions, and patient preferences. 

• Relative indications for raising the target glycemic goal include inability or unwillingness to 

adhere to a more intensive regimen, or an unacceptable risk of hypoglycemia relative to 

anticipated benefits of near-normal glycemia. 

• If the target range remains appropriate but has not been reached, the provider and patient 

should identify the reasons why the target has not been achieved and take appropriate action.

Recommendation

17. We recommend against the use of split mixed insulin regimen for all hospitalized patients with 

type 2 diabetes.

(Strong against | Reviewed, New-added)

Discussion

Split mixed insulin regimen is a twice-a-day insulin injection regimen with a fixed amount of mixed 

neutral protamine Hagedorn (NPH) insulin (intermediate-acting insulin) and regular insulin. This insulin 

regimen requires consistent meal times and compositions to avoid hypoglycemia. Only two small studies 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 44 of 160

could be identified to evaluate the effectiveness of split mixed insulin regimen versus basal-bolus insulin 

for hospitalized patients. It is important to note that the overall quality of evidence from these two trials 

is low to very low due to small sample sizes, poorly matched treatment arms, and concerns about 

generalizability to more broadly representative populations, including the VA/DoD patient population. 

Bellido et al. enrolled a total of 72 patients to compare split mixed to basal-bolus, with early termination 

of the trial due to increased risk for hypoglycemia in the split mixed treatment group.[115] Variations 

between the baseline patient characteristics and meal plans make this evidence difficult to generalize to 

other patient populations, but the potential harm due to hypoglycemia is important to consider. 

Umpierrez et al. compared the use of a basal-bolus insulin regimen to a split mixed insulin regimen in 

130 patients.[116] Rates of hypoglycemia did not significantly vary between treatment groups in this 

study. In both of these studies, baseline blood glucose and HbA1c did not vary between treatment 

groups, mean daily blood glucose measurements did not significantly vary between groups, and there 

were no differences between treatment groups according to length of hospital stay.[115,116]

These studies did not identify any benefit of using the split mixed insulin regimen over a basal-bolus 

insulin regimen for hospitalized patients. Split mixed regimens require consistent meal plans in order to 

avoid hypoglycemia, which is difficult to provide in the hospital. In conclusion, due to the potential 

harms of split mixed insulin and lack of any demonstrable benefit over basal-bolus insulin, we 

recommend against the use of split mixed insulin in hospitalized patients.

Recommendation

18. We suggest a regimen including basal insulin and short-acting meal time or basal insulin and 

correction insulin for non-critically ill hospitalized patients with type 2 diabetes.

(Weak for | Reviewed, New-added)

Discussion

Key factors to consider in devising a glucose control strategy are pre-hospital total daily dose of insulin, 

calorie and carbohydrate intake, other factors that can decrease insulin sensitivity (e.g., physiologic 

stressors, corticosteroids) or increase insulin sensitivity (e.g., renal failure, liver failure), and ease of 

implementation.

The physiologic human pancreas constantly secretes some “basal” insulin while fasting, and releases a 

“bolus” of insulin to cover the glucose load associated with food intake to maintain euglycemia. In 

patients with insulin deficiency (e.g., T1DM, long-standing T2DM, pancreoprivic diabetes), providing 

these modes of insulin action and adding a “pre-meal supplemental correction” insulin to cover for 

unanticipated glucose elevations will best replicate this physiology with intermittent subcutaneous 

insulin. This is referred to as a basal-bolus plus correction regimen.

Basal-bolus plus pre-meal correction regimens are underutilized in the hospital, possibly due to their 

complexity, provider fear of hypoglycemia, and poorly established patient home total daily insulin dose. 

Thus, many patients are prescribed correction insulin only, dosed based upon a number of units 

assigned to treat a pre-specified glucose range on a scale or table called sliding scale insulin (SSI). While 

sliding scale only regimens may be easiest to start, in surgical patients, utilization of basal-bolus over SSI 

alone reduced the risk of post-surgical complications.[111]
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 45 of 160

In terms of ease, a simple basal insulin dose plus pre-meal correction scale may seem more 

approachable to providers and is supported by a single study in which general medical and surgical 

patients with T2DM treated with diet, oral antidiabetic agents, or low-dose insulin at home were shown 

to have similar glycemic control and frequency of hypoglycemic events on a basal-bolus plus correction 

versus basal-bolus regimen. Both regimens resulted in better glycemic control and in fewer treatment 

failures than did the use of SSI alone.[117]

Another practice that requires more study is the application of before-bed correction insulin. In a single 

RCT, before-bed correction did not improve pre-breakfast fasting glucose levels, overall glycemic 

control, length of hospitalization, or hospital complications. While before-bed correction did not lead to 

increased rates of hypoglycemia, this study was underpowered for this outcome, and the risks from 

hypoglycemia, added complexity, and increased nursing workload suggest that routine use of beforebed correction should not be used.[114]

Recommendation

19. We suggest providing medication education and diabetes survival skills to patients before 

hospital discharge.

(Weak for | Reviewed, Amended)

Discussion

Although inpatient DSME is recommended by the Joint Commission, there is relatively little high quality 

supporting evidence for this recommendation. There are several potential times that DSME educators 

might target to provide care for patients with DM: at diagnosis, annually (to assess education, nutrition, 

and emotional needs), when new complicating factors influence self-management, and when transitions 

in care occur.[118] Diabetes care in the outpatient setting involves significant patient engagement, 

including dietary considerations, physical activity, home glucose testing, and medication management. 

The inpatient setting may provide an opportunity for providing education regarding self-management 

skills, including strategies (“survival skills”) for addressing hypoglycemia and hyperglycemia, SMBG, and 

sick day management. Theoretically, providing education on self-management of diabetes could impact 

the overall quality of care. Conversely, the inpatient setting might not be ideal for providing such 

education. The patient will likely have competing medical concerns which precipitated the hospital 

admission, and the inpatient stay is frequently fast-paced and involves procedures and testing. Thus, it is 

also possible that such training would be ineffective because patients would be unable to reliably 

engage and comprehend the care management recommendations. 

Observational studies suggest that there may be some benefit from inpatient DSME, but this evidence is 

prone to bias given the nature of the study.[119] One small RCT examined the effect of inpatient DSME

on outpatient outcomes for up to a year.[120] Although most outcomes (patient satisfaction, hospital 

readmission, and glycemic control at 12 months) were not different between intervention (multidisciplinary diabetes education) and control (usual care), there was an improvement in HbA1c at 12 

months for insulin naïve patients who received the intervention. Despite being an RCT, this study was 

limited due to small sample size and imprecision, and was judged to be of very low quality evidence to 

support inpatient diabetes education. Another RCT compared patients who received diabetes education 

from a pharmacist prior to discharge to usual care.[121] The primary outcomes were medication 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 46 of 160

adherence (using refill data) at three months and glycemic control at four months after discharge. 

Patients receiving the intervention had greater medication adherence and better glycemic control at 

follow-up. However, this study was of low quality due to methodological issues and high dropout rate;

the overall evidence to support inpatient diabetes education was very low.

There are significant gaps in the evidence to support recommendations for inpatient diabetes education. 

There is inadequate evidence to assess which patients with diabetes might benefit most from inpatient 

education; there are no high quality studies that have assessed for patient harms. Nonetheless, we 

suggest providing medication education, and basic information and skills (“survival skills”) to patients 

before discharge. Although the strength of evidence for this recommendation is low, it is likely that 

benefits outweigh harms or burden.

E. Selected Complications

Recommendation

20. We recommend performing a comprehensive foot risk assessment annually.

(Strong for | Not Reviewed, Amended)

Discussion

A foot risk assessment is recommended on an annual basis. A complete foot risk assessment 

includes:[122]

• Evaluation of the skin: breakdown, callus, erythema, tinea pedis

• Assessment of protective sensation using the Semmes-Weinstein 5.07 monofilament

• Evaluation for lower extremity vascular disease: pallor on elevation, dependent rubor, pitting 

edema, and pedal pulses 

• Evaluation for foot and/or nail deformities, trauma

• Prior history of ulcers or amputations

• Evaluation of patient’s footwear and socks

There are no harms associated with a diabetic foot risk assessment. It also offers the opportunity to 

reinforce the importance of regular foot exam by the patient. Patients with diabetes are at risk for 

developing peripheral neuropathy with loss of sensation. Patients who develop peripheral vascular 

disease or ESRD are considered high-risk for developing a foot ulcer.[122-124] There are moderate 

resources needed to accomplish this task, primarily the minimal cost of the monofilament and added 

time at the appointment.

Protective and prophylactic foot care and early detection of any deformity or skin breakdown may 

prevent the development of ulcers and risk of amputation. A person who has had a foot ulcer is at lifelong risk of further ulceration.[122-124]

Peripheral vascular diseases are associated with diabetic bilateral amputation. Preventative foot care 

programs should focus on peripheral vascular assessment to identify patients at risk and on the 

development of timely intervention strategies.[125]
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 47 of 160

The tensile strength of mature scar tissue is about 80% of original tissue strength, thus increasing the 

chance of developing further ulceration. The patient should therefore be questioned about foot ulcer 

history. Further research is required to determine the effectiveness of patient/primary care team 

sensation testing as part of self-management and if this increased engagement decreases the frequency 

of poor foot outcomes.

Recommendation

21. We recommend referring patients with limb-threatening conditions to the appropriate level of 

care for evaluation and treatment.

(Strong for | Not Reviewed, Amended)

Discussion

The confidence in the quality of evidence for this recommendation is low. However, clinical observations 

on the natural course of untreated limb-threatening conditions suggest that the equipoise necessary to 

obtain stronger evidence, such as RCTs, does not exist, and recommendations therefore need to be 

based on lower levels of evidence. The practice of referring patients with limb-threatening conditions is 

supported by the Work Group, which concluded that the benefits most likely strongly outweigh any 

potential harm for the patient.[122] Additionally, most patients are expected to value an expert 

evaluation and opinion on a limb-threatening condition; therefore, patients’ values and preferences are 

unlikely to vary significantly. There are, however, cost considerations associated with utilizing more 

specialty care and potential resource and equity issues regarding the availability of these specialists in 

smaller and remote communities. With these considerations, and considering that this is a 

recommendation carried forward from the previous version of the guideline, the Work Group felt that it 

was appropriate to maintain a strong recommendation. In the unfortunate circumstances when 

amputation is necessary, clinicians may want to refer to the VA/DoD Clinical Practice Guideline for the 

Rehabilitation of Lower Limb Amputation (VA/DoD Lower Limb Amputation CPG).

15

Below is a non-exhaustive list of conditions that should prompt the primary care provider to consider a 

timely referral to a specialist.

Systemic or Ascending (Worsening) Infection

Limb-threatening conditions could include signs and symptoms of systemic infection including gas 

gangrene, ascending cellulitis, and lymphangitis or gangrene.

Although infection is not always clinically apparent, common signs and symptoms include perilesional 

warmth, erythema, purulent drainage, odor, and involvement of bone. Pain may or may not be present. 

There may or may not be lymphangitis and lymphadenopathy, and fever and white blood cell count may 

or may not be present. Sudden loss of glycemic control often heralds serious infections.[126]

 15 See the VA/DoD Clinical Practice Guideline for the Rehabilitation of Lower Limb Amputation. Available at: 

http://www.healthquality.va.gov/guidelines/Rehab/amp/
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 48 of 160

Vascular Compromise

Absence of palpable pedal pulses – Examine the patient to determine presence of dorsalis pedis and 

posterior tibial pulses. Absent pulses and signs of acute ischemia (e.g., rest pain associated with 

dependent rubor with pallor, palpably cold extremities) warrant urgent referral to a vascular surgeon.

Acute ischemia or rest pain –Evidence of arterial insufficiency: lower limb pain at rest, dusky/blue or 

purple/black color, gangrene, or cold extremity. Pain in the toes or forefoot may be relieved by 

dependency of the limb. Assessment is needed for prompt vascular/surgical intervention. Patients with 

acute arterial occlusion will present with pain, pallor, pulselessness, paresthesia, and/or paralysis.[126]

Claudication – Severe claudication is determined by pain in the thigh or calf that occurs when walking 

less than one block and is relieved by rest. 

Foot Ulceration

Cutaneous erosion with a loss of epithelium that extends to or through the dermis can involve deeper 

tissue and is characterized by an inability to self-repair in a timely and orderly manner.[122,127-130]

Puncture Wound

A puncture wound is a lesion through the epidermis, dermis, and any other tissues caused by a piercing 

or penetrating object. Patients with diabetes with puncture wounds can quickly develop severe limbthreatening complications.

Ingrown Toenail

Ingrown toenail presents as a nail plate that has pierced the surrounding periungual tissue with 

associated erythema and drainage or an area of thick or discolored callus. The primary care provider 

should consider referral to a podiatrist for excision of infected ingrown nails, especially in the case of 

high-risk patients.[131]

Hemorrhagic Callus with or without Cellulitis

Patients with hemorrhagic callus with or without cellulitis should be promptly referred to a foot care 

specialist for complete evaluation and treatment. The provider must determine if the cellulitis may be 

associated with callus tissue or necrotic tissue that may obscure an underlying ulceration or deeper 

infection. The callus tissue must be debrided to properly assess the extent of an underlying ulceration 

and possible deeper, more serious infection. Necrotic tissue must also be debrided to help eradicate the 

infection and determine the full extent of the infection. 

Further research is required to better compare outcomes in patients being seen by specialists versus 

primary care for non-urgent conditions, such as ingrown toenails.

Recommendation

22. We recommend a retinal examination (e.g., dilated fundus examination by an eye care 

professional or retinal imaging with interpretation by a qualified, experienced reader) be used to 

detect retinopathy.

(Strong for | Not Reviewed, Amended)
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 49 of 160

Discussion

The quality of the eye examination is a critical factor in the ability to detect early retinopathy. Thus, only 

qualified eye care professionals or trained readers using validated imaging techniques should be utilized 

for retinopathy screening and surveillance. Ophthalmoscopy should be performed through dilated pupils 

using high magnification and stereo viewing. Fundus photography is also highly sensitive in detecting 

clinically significant retinopathy and, when combined with interpretation by an experienced reader, may 

exceed the sensitivity of ophthalmoscopy in retinopathy detection. Non-mydriatic digital retinal imaging 

(i.e., fundus photography through a non-dilated pupil) also provides excellent sensitivity.[132] In some 

cases small pupils and/or media opacities will cause image degradation.[133] The combination of nonmydriatic digital retinal imaging with referral to an eye care specialist for patients in whom image quality 

is sub-optimal is an appropriate screening strategy as it can achieve a high level of sensitivity in the 

detection of retinopathy. In some cases, selective use of mydriatic eye drops to facilitate improved 

image quality will enhance the diagnostic utility of digital retinal imaging.

Recommendation

23. We suggest screening for retinopathy at least every other year (biennial screening) for patients 

who have had no retinopathy on all previous examinations. More frequent retinal examinations 

in such patients should be considered when risk factors associated with an increased rate of 

progression of retinopathy are present. Patients with existing retinopathy should be managed in 

conjunction with an eye care professional and examined at intervals deemed appropriate for the 

level of retinopathy.

(Weak for | Not Reviewed, Amended)

Discussion

Patients with an acute change in vision or a change in ocular function should be urgently referred to an 

eye care provider. Symptoms such as blurring or loss of vision, severe pain or light sensitivity, double 

vision, distortion, floaters, or light flashes may indicate a serious ocular problem. Such complaints 

require urgent referral to an eye care provider. Visual symptoms clearly associated with fluctuations in 

blood glucose should be distinguished from those that are not as the former will typically resolve as 

glycemic control is improved. Nevertheless, it is prudent to seek consultation with an eye care provider 

in all instances where there has been a sudden change in vision. 

Pregnancy may be associated with rapid deterioration of existing retinopathy and a higher risk of 

progression to vision threatening disease. A woman with pre-existing diabetes who becomes pregnant 

should be examined at the time of diagnosis and if she has greater than minimal retinopathy, repeat 

examinations should be performed at four to six week intervals. Proliferative retinopathy or clinically 

significant macular edema should be treated promptly. Those with less severe retinopathy should be 

monitored closely throughout their pregnancy (i.e., during each trimester). In the absence of an eye 

examination within the previous 12 months, patients who are pregnant should have an expedited 

appointment for a retinopathy evaluation. In addition, regardless of the timing of the last eye 

examination, the patient’s eye care provider should be notified of the pregnancy.[134]

Patients with newly diagnosed T2DM may have had several years of sub-clinical or clinical diabetes prior 

to being diagnosed. Retinopathy can develop during this time and up to 40% of patients will have 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 50 of 160

evidence of diabetic eye disease at the time their diabetes is diagnosed. Although the prevalence of 

vision threatening retinopathy at the time of diagnosis is very low, there is a 3-4% prevalence of 

proliferative retinopathy within the first few years of disease. Consequently, it is recommended that 

patients with new onset T2DM who have not had a dilated eye examination within the prior 12 months 

should have one performed within six months.[135]

The inability of symptoms alone to accurately predict the presence or severity of retinopathy 

necessitates regularly scheduled retinal examinations for patients with diabetes. Some patients will 

remain retinopathy-free for several years, but the course of diabetic eye disease cannot be reliably 

predicted for a given individual. Risk factors for progression of retinopathy include: poorly controlled 

HbA1c (e.g., >9.0%), rapid and substantial HbA1c improvement (a decrease of approximately 2% or 

greater over <6 months), insulin use, the presence of microvascular disease including pre-existing 

retinopathy, nephropathy or cardiac autonomic neuropathy, longer duration of disease, hyperlipidemia, 

and poorly controlled blood pressure (e.g. systolic >160 mmHg). In light of these associations, it is 

prudent to perform more frequent retinal examinations in such patients. Clinicians should exert caution 

in extending biennial examinations to patients with factors associated with a higher likelihood of 

retinopathy progression.[135,136]

Retinopathy of any level can progress rapidly over the course of a year and occasionally even mild 

retinopathy will progress to proliferative retinopathy within that time frame. As follow-up intervals 

shorter than 12 months may be indicated for some of these individuals, patients with retinopathy who 

have not had a retinal exam within the previous year should be referred for an expedited retinal 

evaluation. Patients who have previously undergone laser therapy have already reached the stage of 

vision threatening diabetic eye disease.[135] These patients require close follow-up and in the absence 

of information to the contrary should be considered at high risk for vision loss and receive an expedited 

examination if they have not had one within the previous year.

Duration of disease is most strongly associated with retinopathy in individuals with T1DM. The 

prevalence of proliferative retinopathy approaches 30% after 15 years of diabetes and may rise to as 

much as 50% after 20 years. Although the prevalence of proliferative disease is lower in T2DM, the 

prevalence of any retinopathy approaches 75% in insulin-treated patients with longer duration of 

diabetes and the prevalence of proliferative retinopathy may exceed 20%. Different patients may exhibit 

separate and unique rates of retinopathy development or progression, but the likelihood of ocular 

involvement increases with duration of diabetes.[137]

Recommendations

24. We recommend that all females with pre-existing diabetes or personal history of diabetes and 

who are of reproductive potential be provided contraceptive options education and education 

on the benefit of optimizing their glycemic control prior to attempting to conceive.

(Strong for | Not Reviewed, Amended)

25. We recommend that all females with pre-existing diabetes or personal history of diabetes who 

are planning pregnancy be educated about the safest options of diabetes management during 

the pregnancy and referred to a maternal fetal medicine provider (when available) before, or as 

early as possible, once pregnancy is confirmed.

(Strong for | Not Reviewed, Amended)
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 51 of 160

Discussion

Hyperglycemia in pregnancy results in significantly elevated risks of both fetal and maternal harm; many 

routine medications used in T2DM are contraindicated during pregnancy. Achieving glycemic control 

with recommended medications before pregnancy may prevent adverse outcomes and is encouraged 

whenever possible.[138] This can be best achieved through a coordinated effort between the patient, 

family, and care providers encompassing the patient’s desires, lifestyle, advanced planning, and 

personal beliefs. Because of the high-risk nature of pregnancy complicated by diabetes and the need for 

intensive multidisciplinary monitoring and patient support, referral of women with diabetes to an expert 

high-risk perinatal team at the earliest possible opportunity must be considered as the standard of care. 

Ideally, such a referral should be made during the period of planned conception. While intervention 

studies will not be available to prove improved outcomes with diabetes management, significant fetal 

and maternal complications, including death and fetal demise, have been consistently associated with 

increasing HbA1c. As a result of these adverse outcomes, achieving a pre-pregnancy HbA1c of <7.0% is 

optimal. For further reference, please see the VA/DoD Clinical Practice Guideline for Management of 

Pregnancy [VA/DoD Pregnancy CPG]16).

Fetal complications of maternal hyperglycemia include:[138]

• Congenital malformations

• Stillbirth 

• Macrosomia 

• Neonatal delivery-related trauma 

• Neonatal hypoglycemia 

Maternal complications that occur at above average rates in diabetic pregnancies include:[138]

• Preeclampsia 

• Hypertension 

• Preterm labor 

• Need for cesarean section

In addition to providing intensive glycemic control, the clinician overseeing the management of 

pregnant women should:[138]

• Prescribe supplemental folic acid and a dietetic regimen to ensure appropriate caloric intake 

during pregnancy 

• Screen for autoimmune thyroid disease, hypertension, and kidney disease

 16 See the VA/DoD Clinical Practice Guideline for Management of Pregnancy. Available at: 

http://www.healthquality.va.gov/guidelines/WH/up/index.asp
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 52 of 160

VII. Pharmacological Therapy

When individualized glycemic goals are not achieved with nonpharmacological therapy such as diet

and physical activity, adjunctive therapy with medications is indicated (see Recommendation 5 for a 

discussion of evidence regarding glycemic control). The magnitude of the reduction in HbA1c necessary 

to achieve goals should be considered when choosing medications and when assessing hypoglycemia 

risk, weight gain, patient preferences, administration burden, and cost (see Recommendations 4 and 7). 

For treatment of DM in obese patients, see the VA/DoD Obesity CPG.

17

Considerations 

The evidence for pharmacological treatment options for T2DM was not systematically reviewed as part 

of this guideline update; therefore, formal recommendations could not be made. The rationale to not 

systematically review the evidence for pharmacotherapy was that the evidence in this area is rapidly 

evolving and therefore any recommendations made may be outdated during the lifetime of this 

guideline. In lieu of recommendations, the following considerations are offered based on usual care and 

recent SRs performed by other groups. Where applicable, users of this guideline are asked to refer to 

their respective agencies for guidance/criteria on the use of pharmacotherapy for T2DM that are based 

on the most current evidence. 

The following considerations are based on usual care and SRs performed by other groups: 

1. When selecting an agent, consideration must be given to efficacy, contraindications, drug

interactions, comorbidities, and potential side effects. Discuss with patients the various

treatment options and arrive at a shared treatment plan. (See Appendix B)

2. Insulin should be considered as initial therapy in any patient with hyperglycemia with significant

symptoms, if ketosis is present, and in newly diagnosed or previously unrecognized T1DM.

3. Metformin should be given as the first-line agent unless there are contraindications.

4. In patients with metformin intolerance or contraindications, other drug classes can be

considered. These include (not in order of preference): alpha-glucosidase inhibitors (AGIs),

dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) agonists, insulin,

meglitinides, sodium glucose co-transporter 2 (SGLT2) inhibitors, sulfonylureas (SU), and

thiazolidinediones (TZDs).

5. When initial therapy no longer provides adequate glycemic control, addition of a second-line

agent from another class rather than substitution is usually necessary. Substitution can be

reserved for intolerance/adverse effect to a drug. Combination of two anti-hyperglycemic drugs

has the benefit of reducing hyperglycemia by working on different mechanisms that cause

hyperglycemia (refer to Figure 1). Some agents are not generally used in combination or have not

been studied in combination (refer to Appendix C). Although the evidence is clear on the relative

efficacy of the various medications, their usage needs to be guided by clinical considerations.

17 See the VA/DoD Clinical Practice Guideline for Screening and Management of Overweight and Obesity. Available at: 

http://www.healthquality.va.gov/guidelines/CD/obesity/
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 53 of 160 

6. Addition of basal insulin to existing regimen should be considered, particularly if the desired 

decrease in HbA1c is not likely to be achieved by use of combination therapy. 

7. Patients and their families should be instructed to recognize and confirm their understanding of 

signs and symptoms of hypoglycemia and its management.

8. Given that new studies and FDA alerts will be published subsequent to the release of this

guideline, clinicians should refer to the criteria for use published by the VA Pharmacy Benefits 

Management program (VA PBM) and the Department of Defense Pharmacy and Therapeutics 

Committee (DoD P&T).

Figure 1: Sequential Treatment of Type 2 Diabetes* 

Abbreviations: DPP-4: dipeptidyl peptidase-4; DSME: diabetes self-management and education; GLP-1: glucagon-like peptide-1; 

SGLT2: sodium glucose co-transporter 2

*Bile acid sequestrants, bromocriptine quick release, and pramlintide are uncommonly used agents in the management of 

diabetes and are not included in this guideline.

†Consider a trial of metformin extended-release in those with persistent adverse gastrointestinal effects from metformin 

immediate-release

†Second-line agents listed alphabetically; not in order of preference ‡If applicable, refer to VA (http://www.pbm.va.gov/) or DoD (http://www.health.mil/PandT) guidance/criteria for further

recommendations on use of these agents
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 54 of 160

Table 3: Primary Action of Agents Used to Treat Hyperglycemia* [139] 

Agent Action Results

α-glucosidase inhibitors Inhibits intestinal α-glucosidase Delays intestinal carbohydrate absorption/

digestion

DPP-4 inhibitors Increases concentration of GLP-1 by slowing 

its inactivation via DPP-4 enzyme 

Glucose dependent; ↑ insulin secretion

Glucose dependent; ↓ glucagon secretion

GLP-1 agonists Activates GLP-1 receptors ↑ glucose dependent insulin secretion

↓ glucose dependent glucagon secretion

Slows gastric emptying

Insulin Activates insulin receptors ↓ hepatic glucose production

↑ glucose uptake by fat and muscle cells

Meglitinides Inhibits ATP-dependent potassium 

channels on pancreatic β-cells

↑ insulin secretion

Metformin Activates AMP-kinase ↓ hepatic glucose production

↑ peripheral glucose uptake 

SGLT2 inhibitors Inhibits SGLT2 in proximal tubule thereby 

reducing reabsorption of filtered glucose 

↑ urinary glucose excretion 

Sulfonylureas Inhibits ATP-dependent potassium 

channels by binding to specific sulfonylurea 

receptor on pancreatic β-cells

↑ insulin secretion

Thiazolidinediones Activates PPAR-γ receptors in adipose 

tissue, skeletal muscle, liver

↓ hepatic glucose production

↑ peripheral glucose uptake

* Agents listed in alphabetical order

Abbreviations: AMP: 5’ adenosine monophosphate-activated protein; ATP: adenosine triphosphate; DPP-4: dipeptidyl

peptidase-4; GLP-1: glucagon-like peptide-1; PPAR: peroxisome proliferator-activated receptor; SGLT2: sodium glucose cotransporter 2

A. Summary of the Evidence - Monotherapy and Non-Insulin Two-Drug

Combination Therapy

Three SRs by the Agency for Healthcare Research and Quality (AHRQ) have evaluated the comparative 

effectiveness and safety of diabetes medications.[140-143] The most recent review includes publications 

through December 2015. The evidence supports metformin as a first-line agent to treat T2DM based on 

its benefit-to-risk profile. A summary of the findings of the AHRQ reviews are summarized below.

a. Reduction in HbA1c

When used as monotherapy, metformin, SUs, TZDs, and repaglinide produced a similar reduction in 

HbA1c of about 1%. The α-glucosidase inhibitors and nateglinide reduced HbA1c to a lesser extent 

(approximately 0.5%).[140] The DPP-4 inhibitors were found to be less effective in lowering HbA1c

compared to SU and metformin with treatment differences of 0.2% and 0.4%, respectively.[141-143] 

The GLP-1 agonists and SGLT2 inhibitors were not included in the monotherapy assessments. The 

product labeling does not recommend the GLP-1 agonists as first-line therapy; however, they have been 

studied as monotherapy. Comparative trials with dulaglutide and once-weekly exenatide showed 

reductions in HbA1c comparable to metformin and pioglitazone and greater than sitagliptin.[144,145] 

Another trial showed greater reduction in HbA1c with liraglutide compared to glimepiride in patients 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 55 of 160

who were either diabetes treatment naïve or who were on prior SU at half-maximal dose.[146] As 

monotherapy, the average HbA1c reduction with the SGLT2 inhibitors is less than 1%. In a comparative 

study, empagliflozin was found to be comparable to sitagliptin.[147]

Metformin plus a second agent provided additional HbA1c lowering, ranging from 0.4% to 1.0% over 

metformin alone.[141-143] Comparisons of various two-drug metformin-based regimens show similar 

reduction in HbA1c (metformin + SU, metformin + TZD, metformin + DPP-4 inhibitor, metformin + SGLT2 

inhibitor). However, metformin + GLP-1 agonists reduced HbA1c more than metformin + DPP-4 

inhibitors (treatment difference: 0.65%).[142,143]

b. Weight

SUs, TZDs, and meglitinides are associated with weight gain, while the GLP-1 agonists and SGLT2 

inhibitors are associated with weight loss. Metformin, DPP-4 inhibitors, and α-glucosidase inhibitors are 

generally considered to be weight neutral. 

Direct comparison among the drugs associated with weight gain show the increase in weight is similar 

between SUs and meglitinides and less than TZDs. Among the weight neutral drugs, weight loss favored 

metformin compared to DPP-4 inhibitors.[141-143]

c. Hypoglycemia

SUs have a greater risk for hypoglycemia as monotherapy than metformin, TZDs, DPP-4 inhibitors, and 

GLP-1 agonists. In two-drug combination treatment comparisons, the risk of hypoglycemia with 

metformin + SU was greater than metformin + DPP-4 inhibitor, metformin + SGLT2 inhibitor, metformin 

+ GLP-1 agonist, or metformin + TZD. The risk of hypoglycemia was similar between metformin 

monotherapy and two-drug regimens of metformin plus a second agent (TZD, DPP-4 inhibitor, SGLT2 

inhibitor).[141-143]

d. Blood Pressure

Metformin, SUs, and TZDs had minimal effect on systolic and diastolic blood pressure.[140] The GLP-1 

agonists and SGLT2 inhibitors decreased systolic blood pressure by 3-5 mmHg compared to metformin, 

SUs, and DPP-4 inhibitors.[142,143]

e. Gastrointestinal (GI) Adverse Effects

Metformin, GLP-1 agonists, and acarbose are associated with more GI side effects (e.g., nausea, 

vomiting, diarrhea) than SUs, TZDs, and DPP-4 inhibitors.[140-143] The SGLT2 were not included in the 

comparisons, but are typically not associated with increased GI side effects.

f. Lipids

The TZDs are associated with increase in low-density lipoprotein cholesterol (LDL-C) and metformin is 

associated with decrease in LDL-C. The SUs, DPP-4 inhibitors, acarbose, and repaglinide have little effect 

on LDL-C. In comparative analyses, metformin decreased LDL-C levels relative to SUs, DPP-4 inhibitors, 

and TZDs.[140,141] 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 56 of 160

Pioglitazone increased HDL-C more than rosiglitazone, metformin, and SUs. The effect on HDL-C with 

metformin was comparable to SUs or rosiglitazone and greater than DPP-4 inhibitors. However, the

combination of metformin + rosiglitazone significantly increased HDL-C compared to metformin + SU.[141] 

TZDs increased HDL-C whereas the other agents had little impact on HDL-C. Only rosiglitazone was

shown to slightly increase triglycerides.

Lipids were not addressed in the most recent AHRQ review; therefore, comparative data for the GLP-1 

agonists and SGLT2 inhibitors were not available. An SR and network meta-analysis found that GLP-1 

agonists were associated with modest reduction in LDL-C and triglycerides, but no significant increase in

HDL-C.[148] 

Metformin, TZDs, SUs, DPP-4 inhibitors, acarbose, repaglinide, SGLT2 inhibitors, and GLP-1 agonists have

been associated with various changes in lipid values as noted; however, whether these changes result in

reductions in important clinical outcomes (fewer MIs, stroke, or improved total mortality) is unknown. 

Please refer to the VA/DoD Clinical Practice Guideline for the Management of Dyslipidemia for 

Cardiovascular Risk Reduction [VA/DoD Dyslipidemia CPG].18

g. Cardiovascular Mortality and Morbidity

Metformin was associated with a lower risk for cardiovascular mortality compared to SUs. There were 

insufficient data to directly compare the other agents. Non-comparative long-term cardiovascular trials

have been published for saxagliptin, alogliptin, sitagliptin, empagliflozin, liraglutide, and lixisenatide and

are discussed later.

h. Other Adverse Effects

There were insufficient comparative data on other adverse effects associated with specific drugs or drug

classes. Refer to Appendix B for adverse effects associated with each drug class.

B. Triple Therapy

A network meta-analysis evaluating triple therapy combinations found that the addition of a third agent

to dual therapy results in further reduction of HbA1c. Changes in weight were consistent with what is

expected for a given drug class. The odds of hypoglycemia increased when a third agent was added to

dual therapy. The DPP-4 inhibitors had the lowest odds of hypoglycemia and SUs and insulin had the 

highest odds.[149] 

Compared to dual therapy alone:

• The addition of a DPP-4 inhibitor to dual therapy further decreased HbA1c (estimated treatment

difference: -0.56%, 95%CI: -0.70 to -0.42). There was no appreciable change in weight.

• The addition of a SGLT2 inhibitor to dual therapy further decreased HbA1c (estimated treatment

difference -0.69%, 95%CI: -0.92 to -0.46) and decreased weight (estimated treatment difference:

-1.79 kg, 95%CI: -3.03 to -0.55).

18 See the VA/DoD Clinical Practice Guideline for the Management of Dyslipidemia for Cardiovascular Risk Reduction. Available at: 

http://www.healthquality.va.gov/guidelines/CD/lipids/
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 57 of 160

• The addition of a GLP-1 agonist to dual therapy further decreased HbA1c (estimated treatment

difference: -0.81%, 95%CI: -1.00 to -0.62) and decreased weight (estimated treatment

difference: -1.85 kg, 95%CI: -2.85 to -0.89).

• The addition of a TZD to dual therapy further decreased HbA1c (treatment difference: -0.94%,

95%CI: -1.18 to -0.70), but increased weight (estimated treatment difference: 2.72 kg, 95%CI:

1.45 to 3.99).

• The addition of a SU to dual therapy further decreased HbA1c (treatment difference: -0.59%,

95%CI: -0.90 to -0.28), but increased weight (estimated treatment difference: 3.23 kg, 95%CI:

1.56 to 4.90).

• The addition of insulin to dual therapy further decreased HbA1c (treatment difference: -0.91%,

95%CI: -1.13 to -0.69), but increased weight (estimated treatment difference: 2.34 kg, 95%CI: 1.18

to 3.50).

Direct comparison of non-insulin containing triple therapy regimens 

There are few head-to-head trials comparing non-insulin containing triple therapy regimens. Most trials 

compared a third agent as add-on to metformin + SU. All treatments provided additional HbA1c 

lowering; however, differences between treatments were relatively small. The impact on weight favored 

those drugs that are known to cause weight loss. 

Table 4: Trials comparing non-insulin containing triple therapy regimens 

Trial Author

Comparators

(First drug – 

second drug)

Addedon toDurati

on

HbA1c 

(treatment 

difference)

Weight

(treatment 

difference) Hypoglycemia

DeRosa [150] DPP-4 versus SU MET+TZ

D 

52 

weeks Similar decrease -6.5 kg N/A

Liu [151] TZD versus DPP-4 MET+SU 24 

weeks -0.23% (p=NS) 1.6 kg N/A

Schernthaner 

[152] 

SGLT2 versus DPP4 MET+SU 52 

weeks

-0.37%

(95% CI: -0.50 to -0.25) -2.4 kg Similar

Home [153] GLP-1 versus TZD MET+SU 52 

weeks

0.25%

(95% CI: 0.10 to 0.40)

-4.8 kg 31.4% versus 

21%

Abbreviations: CI: confidence interval; DPP-4: dipeptidyl peptidase-4; GLP-1: glucagon-like peptide-1; kg: kilograms; MET: 

metformin; N/A: Not applicable; NS: not significant; SGLT2: sodium glucose co-transporter 2; SU: sulfonylurea; TZD: 

thiazolidinedione

C. Insulin Therapy

Insulin requirements vary widely among people with diabetes, even when other factors are similar. 

Types, frequency, and dosages of insulin must be individualized, considering the following factors:

• Type of diabetes

• Age

• Weight (presence or absence of obesity)

• Comorbid conditions
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 58 of 160 

• Presence of autonomic neuropathy 

• Concomitant medications (specifically beta-blockers)

• Patient’s ability to perform SMBG and accurately inject insulin

• Complexity of management strategy (number of injections, variable dosing based on 

carbohydrate intake and pre-prandial glycemia)

• Risks of hypoglycemia and benefits of tight control, including psychosocial factors 

• Magnitude and pattern of hyperglycemia

• Cost

Many patients with T2DM can achieve their glycemic target with a single bedtime injection of long-acting 

insulin or pre-meal split mixed insulin, often in combination with an oral agent. Some patients will

require intensified regimens to achieve their target glycemic range. Early use of insulin should be 

considered in any patient with extreme hyperglycemia, even if transition to therapy with oral agents is 

intended as hyperglycemia improves. Other insulin options include adding basal insulin (NPH or longacting analog) and continuing therapy with one or two oral agents, adding a premixed insulin while

continuing insulin sensitizers (e.g., metformin) and discontinuing secretagogues, or adding rapid-acting 

insulin at mealtimes and continuing therapy with one or two oral agents.[154] The care of patients with

T1DM or T2DM (needing insulin) should be individualized, in consultation with a multidisciplinary 

diabetes care team. 

The GLP-1 agonists in combination with insulin were not addressed in the 2010 DM CPG and a brief

summary of the evidence is provided. An SR and meta-analysis of 15 studies (N=4,348) of at least eight 

weeks duration addressed combination use of GLP-1 receptor agonists and basal insulin.[155] Eleven 

studies evaluated the addition of a GLP-1 agonist to basal insulin compared to basal insulin alone. Both 

treatment groups allowed the use of oral agents. Four studies compared a GLP-1 agonist to mealtime 

insulin. All patients had background basal insulin with or without oral agents. The primary endpoints 

were change in glycemic control, hypoglycemia, and weight between baseline and end of intervention.

GLP-1 agonist and basal insulin combination treatment compared to other anti-hyperglycemic 

treatments showed a mean reduction in HbA1c of 0.44% (95% CI: -0.60 to -0.29), increased likelihood of 

achieving target HbA1c < 7% (relative risk: 1.92, 95% CI: 1.43 to 2.56), did not have an impact on the risk 

of hypoglycemia (0.99, 95% CI: 0.76 to 1.29) and a mean reduction in weight of -3.22 kg (95% CI: -4.90 to 

-1.54). 

Limitations of the study included the long-term durability of the treatment (mean 24.8 weeks); potential 

risk of bias with some studies having open-label design and pharmaceutical industry funding; differences 

in GLP-1 agonist preparation (short-acting, twice-daily formulations, intermediate once-daily products, 

and long-acting weekly drugs); long-term durability, safety, and side effects of GLP-1 agonists have not 

been established; and the ideal timing for the start of treatment in the clinical course of the 

disease.[155] 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 59 of 160 

Table 5: Insulin: Summary of Pharmacokinetics [139,156-161] 

Insulin Onset Peak Duration Half-life Comments

Prandial (bolus) Insulin

Rapid-Acting 

Insulin aspart NovoLog: 0.2 to 0.3 hr 

NovoLog Mix 70/30: 10 to 

20 mins 

NovoLog: 1 to 3 hrs

NovoLog Mix 70/30: 1 to 

4 hrs

NovoLog: 3 to 5 hrs

NovoLog Mix 70/30: 18 to 

24 hrs

Subcutaneous: 81 min 

(NovoLog); ≈ 8 to 9 hrs

(NovoLog Mix 70/30)

Appearance: clear; 

covers insulin needs at 

the time of the 

injection Insulin lispro Subcutaneous: 0.25 to 

0.5 hr 

Subcutaneous: 0.5 to 

2.5 hrs

Subcutaneous: ≤5 hrs Subcutaneous: ≈ 1 hr, 

IV: 51 to 55 mins

Insulin glulisine 5 to 15 mins 1.6 to 2.8 hr <5 hrs IV: 13 mins, 

Subcutaneous: 42 mins

Short-Acting

Regular insulin Subcutaneous: ≈ 0.5 hr,

IV: 10 to 15 mins 

Subcutaneous: 3 hrs U 100: 4 to 12 hrs; 

U 500: up to 24 hrs

IV: 17 mins, 

Subcutaneous: 86 to 

141 mins 

Appearance: clear; 

covers insulin needs 

for meals eaten within 

30-60 mins

Basal Insulin

Intermediate-Acting

Insulin isophane 

(NPH)

1 to 1.5 hrs 4 to 12 hrs 14.5 hrs ≈ 4.4 hrs Appearance: cloudy; 

covers insulin needs 

for about half the day 

or overnight. Often 

combined with rapidor short-acting insulin

Long-Acting (Not be mixed with other insulins)

Insulin detemir 3 to 4 hrs None Up to 24 hrs 5 to 7 hrs Appearance: clear; 

covers insulin needs 

for about 1 full day. 

Often used as needed, 

or with rapid- or shortacting insulin

Insulin glargine Lantus: 3 to 4 hrs None Lantus: Up to 24 hrs

Toujeo: ≥24 hrs Toujeo: 6 hrs

Insulin degludec 1 hr 9 hrs At least 42 hrs 25 hrs
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 60 of 160 

Insulin Onset Peak Duration Half-life Comments

Pre-Mixed Products

70 NPH/30 Regular Not to be mixed with other insulins. Cloudy/generally taken twice a day before meals.

50 NPH/50 Regular

75 NPH/25 lispro

50 NPH/50 lispro

70 aspart/30 aspart

50 aspart/50 aspart

Abbreviations: hr: hour; IV: intravenous; min: minute; NPH: neutral protamine Hagedorn
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 61 of 160

D. Cardiovascular Outcomes Trials

a. DPP-4 Inhibitors and Cardiovascular Outcomes

The long-term cardiovascular safety trials for saxagliptin (Saxagliptin Assessment of Vascular Outcomes 

Recorded in Patients with Diabetes Mellitus [SAVOR]), alogliptin (Examination of Cardiovascular 

Outcomes with Alogliptin versus Standard of Care [EXAMINE]), and sitagliptin (Trial Evaluating 

Cardiovascular Outcomes with Sitagliptin [TECOS]) were conducted in patients with T2DM who had a 

history of, or were at high risk for, cardiovascular events. The results showed that there was no increase 

or decrease in the primary endpoint (composite of cardiovascular death, nonfatal MI, or nonfatal 

ischemic stroke) between the DPP-4 inhibitors and placebo.[162-164]

A secondary endpoint from the SAVOR trial found a higher risk of hospitalization for heart failure in 

patients receiving saxagliptin relative to placebo (HR=1.27, 95%CI: 1.07 to 1.51, p=0.007). Post-hoc 

analyses of SAVOR found that patients with Class 3 or 4 heart failure, or eGFR < 60mL/min were at a 

greater risk for hospitalization for heart failure. Hospitalization due to heart failure was not a predefined 

endpoint. In the EXAMINE trial for alogliptin, a post-hoc analysis found a numerically higher risk of 

hospitalization for heart failure in patients receiving alogliptin relative to placebo (HR=1.19, 95%CI: 0.90 

to 1.58, p=0.220). A secondary endpoint in the TECOS trial found that the rate of hospitalization for 

heart failure did not differ between sitagliptin and placebo (HR=1.0, 95%CI: 0.83 to 1.20, p=0.98). It is 

unknown if true differences exist between agents as trials did not directly compare one agent to another

and study populations and methodology differed. However, two large observational studies found the 

risk for hospitalization for heart failure was not greater with saxagliptin compared to 

sitagliptin.[165,166] The long-term trial for linagliptin (Cardiovascular Outcome Trial of Linagliptin 

Versus Glimepiride in Type 2 Diabetes [CAROLINA]) is ongoing and expected to be completed in 2019. 

This is the first comparative trial evaluating linagliptin and glimepiride in patients who have early T2DM

and increased cardiovascular risk or established complications. 

The labeling for saxagliptin and alogliptin state that the risks and benefits of saxagliptin or alogliptin 

should be considered prior to initiating treatment in patients at a higher risk for heart failure. Observe 

patients for signs and symptoms of heart failure during therapy. Advise patients of the characteristic 

symptoms of heart failure and to immediately report such symptoms. If heart failure develops, evaluate 

and manage according to current standards of care and consider discontinuation of 

saxagliptin/alogliptin.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 62 of 160

Table 6: DPP-4 Cardiovascular Outcomes Trials 

Study

Treatment 

Arms Outcomes

Target 

Completion 

Date Results

SAVORTIMI [163] 

N=16,500

Saxagliptin 

versus 

placebo

Time to first confirmed 

CV event (a composite 

defined as CV-related 

death, nonfatal MI, 

nonfatal stroke, or 

unstable angina 

requiring hospitalization)

Completed Saxagliptin was non-inferior to placebo. 

Did not increase risk of CV death, MI, or 

stroke, but also did not add any benefits.

EXAMINE 

[164] 

N=5,400

Alogliptin

versus 

placebo

Completed Alogliptin was non-inferior to placebo for 

CV endpoints (composite of death from CV 

causes, nonfatal MI, or nonfatal stroke).

CAROLINA 

[167] 

N=6,115

Linagliptin 

versus 

glimepiride

February 

2019

Pending

TECOS 

[162] 

N=14,000

Sitagliptin 

versus 

placebo

Completed Sitagliptin was non-inferior to placebo for 

CV composite endpoint (first time MI, 

nonfatal stroke, unstable angina requiring 

hospitalization, or CV related death).

Abbreviations: CAROLINA: Cardiovascular Outcome Trial of Linagliptin versus Glimepiride in Type 2 Diabetes; CV: 

cardiovascular; EXAMINE: Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care; MI: myocardial 

infarction; SAVOR-TIMI: Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus - 

Thrombolysis in Myocardial Infarction; TECOS: Trial Evaluating Cardiovascular Outcomes with Sitagliptin

b. Thiazolidinediones and Cardiovascular Outcomes

The long-term cardiovascular trial for pioglitazone (Prospective Pioglitazone Clinical Trial In 

Macrovascular Events [PROactive]) was conducted in patients with T2DM and who had evidence of 

macrovascular disease.[168] There was no significant difference between pioglitazone and placebo in 

the primary endpoint (composite of all-cause mortality, non-fatal MI [including silent MI], stroke, acute 

coronary syndrome, leg amputation, coronary revascularization, or revascularization of the leg) 

(HR=0.90, 95%CI: 0.8 to 1.02, p=0.095). The main secondary endpoint (composite all-cause mortality, 

non-fatal MI, and stroke) showed a significant reduction in events with pioglitazone compared to 

placebo (HR=0.84, 95%CI: 0.72 to 0.98, p=0.027).

Heart failure (non-adjudicated) was reported more often with pioglitazone (10.8%) than placebo (7.5%). 

Hospitalization for heart failure was also reported more frequently with pioglitazone (5.7%) than 

placebo (4.1%).

Another large trial (Insulin Resistance Intervention after Stroke [IRIS]) compared pioglitazone to placebo 

in patients with insulin resistance who had had a recent ischemic stroke or transient ischemic attack 

(TIA). There was a significant reduction in the primary outcome (fatal or nonfatal stroke or MI) with 

pioglitazone compared to placebo (HR=0.76, 95% CI: 0.62 to 0.93, p=0.007).[169] 

In 2013, the Risk Evaluation and Mitigation Strategy (REMS) for rosiglitazone-containing medicines was 

removed by the FDA after determining that data from the Rosiglitazone Evaluated for Cardiac Outcomes 

and Regulation of Glycaemia in Diabetes (RECORD) trial did not show an increased risk of MI. The longterm cardiovascular trial for rosiglitazone (RECORD) was a randomized, multicenter, open-label, noninferiority trial. Patients with T2DM (N=4,447) who were receiving metformin or sulfonylurea and had 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 63 of 160

inadequate glycemic control were randomized to add-on rosiglitazone or placebo (control group). The 

primary end point was hospitalization or death from cardiovascular causes.

Results showed non-inferiority of rosiglitazone compared to placebo. The primary endpoint occurred in 

321 patients in the rosiglitazone group and 323 patients in the control group over the 5.5 year follow up 

period (HR= 0.99, 95% CI: 0.85 to 1.16). Additional results showed non-inferiority for cardiovascular 

death (HR=0.84, 95% CI: 0.59 to 1.18), MI (HR=1.14, 95% CI: 0.80 to 1.63), and stroke (HR=0.72, 95% CI: 

0.49 to 1.06). There was no significant difference between rosiglitazone and the control group regarding 

MI and death from cardiovascular causes or any cause. Similar to pioglitazone, heart failure leading to 

hospitalization was reported more often with rosiglitazone compared to placebo (HR=2.10, 95% CI: 1.35

to 3.27).

c. GLP-1 Receptor Agonists and Cardiovascular Outcomes

Liraglutide is the first of the GLP-1 class to show cardiovascular benefit (Liraglutide Effect and Action in 

Diabetes: Evaluation of Cardiovascular Outcome Results [LEADER] trial) in patients with T2DM and high 

cardiovascular risk.[62] Lixisenatide with T2DM patients who had MI or who had been hospitalized for 

unstable angina, did not show cardiovascular benefit in the Evaluation of Lixisenatide in Acute Coronary 

Syndrome [ELIXA] trial.[170] 

The primary composite outcome in the liraglutide study (LEADER) was a time-to-event analysis of the 

first occurrence of death from cardiovascular causes, nonfatal MI, or nonfatal stroke with a primary 

hypothesis of non-inferiority to placebo. The liraglutide group had significantly fewer patients with the 

primary outcome (HR=0.87, 95% CI: 0.78 to 0.97, p <0.001 for non-inferiority; p=0.01 for superiority). 

The rate of death due to cardiovascular causes (HR=0.78, 95% CI: 0.66 to 0.93, p=0.007) and death from 

any cause (HR=0.85, 95% CI: 0.74 to 0.97, p=0.02) was lower in the liraglutide group than in the placebo 

group. There were non-significant reduction in the rates of nonfatal MI, nonfatal stroke, and 

hospitalization for heart failure in the liraglutide group versus the placebo group. 

The primary composite end point of the lixisenatide study (ELIXA) was cardiovascular death, MI, stroke, or 

hospitalization for unstable angina. Lixisenatide showed non-inferiority to placebo in the primary endpoint event (HR=1.02, 95% CI: 0.89 to 1.17, p<0.001) but did not show superiority (p=0.81). The two groups 

showed no significant differences in the rate of hospitalization for heart failure (HR in the lixisenatide 

group=0.96, 95% CI: 0.75 to 1.23) or the rate of death (HR=0.94, 95% CI: 0.78 to 1.13).

Other cardiovascular safety trials with the GLP-1 class are ongoing (See Table 7).
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 64 of 160

Table 7: GLP-1 Cardiovascular Outcomes Trials* 

Study Treatment Arms Outcomes Target Completion Date

LEADER [62] 

N=9,000

Liraglutide versus 

placebo

Time to first confirmed CV 

event (a composite defined 

as CV-related death, 

nonfatal MI, nonfatal 

stroke, or unstable angina 

requiring hospitalization)

Completed: Reduced the risk 

of major adverse CV events 

EXSCEL [171]

N=14,000

Exenatide once weekly 

versus placebo

April 2018

HARMONY-OUTCOMES 

[172] 

N=9,400

Albiglutide versus 

placebo

May 2019

REWIND [173]

N=9,622

Dulaglutide versus 

placebo

July 2018

ELIXA [170] 

N=6,000

Lixisenatide versus 

placebo

Completed: Not inferior to 

placebo in CV outcomes

SUSTAIN 6 [174]

N=3,299

Semaglutide versus 

placebo

Completed: Reduced the risk 

of major adverse CV events 

* Semaglutide was not FDA approved at the time this guideline was published.

Abbreviations: CV: cardiovascular; ELIXA: Evaluation of Lixisenatide in Acute Coronary Syndrome; EXSCEL: Exenatide Study of

Cardiovascular Event Lowering; GLP-1: glucagon-like peptide-1; LEADER: Liraglutide Effect and Action in Diabetes: Evaluation of

Cardiovascular Outcome Results; MI: myocardial infarction; REWIND: Researching Cardiovascular Events with a Weekly Incretin 

in Diabetes; SUSTAIN 6: Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 

2 Diabetes

d. SGLT2 Inhibitors and Cardiovascular Outcomes

One long-term prospective cardiovascular outcomes trial has been completed with a SGLT2 inhibitor to 

date. The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPAREG OUTCOME) trial evaluated the time to first event of cardiovascular death, non-fatal MI, or non-fatal 

stroke in patients randomized to empagliflozin or placebo.[63] 

The primary composite outcome was statistically significant for patients in the empagliflozin group 

compared to placebo with a 32% relative risk reduction (2.6% ARR) in death from any cause in the 

pooled empagliflozin group. The number needed to treat was 39 patients for three years to prevent one 

death. In terms of death from cardiovascular causes, empagliflozin showed a 38% relative risk reduction 

(2.2% ARR). To prevent one death from cardiovascular causes, 45 patients would need to be treated for 

three years. 

A predefined secondary outcome (composite of the primary outcome plus hospitalization for unstable 

angina) was also statistically significant in the empagliflozin arm revealing a 35% relative risk reduction 

(1.4% ARR) in hospitalization for heart failure. Seventy-one patients would need to be treated for three

years to prevent one hospitalization. Of note, 77% of patients were taking statins concomitantly. This 

study only included patients with a high risk of CVD and did not include patients without CVD.[63] 

Other cardiovascular safety trials with the SGLT2 inhibitor class are ongoing (See Table 8).
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 65 of 160

Table 8: SGLT2 Outcomes Trials 

Study Treatment Arms Outcomes Target Completion Date

CANVAS [175] 

N=4,330

Canagliflozin 

versus placebo

Time to first confirmed CV event (a 

composite defined as CV-related death, 

nonfatal MI, nonfatal stroke, or 

unstable angina requiring 

hospitalization)

February 2017

DECLARE-TIMI

58 [176] 

N=17,276

Dapagliflozin 

versus placebo

Time to first event included in the 

composite endpoint of CV death, MI or 

ischemic stroke 

April 2019

EMPA-REG 

OUTCOME [63] 

N=7,064

Empagliflozin 

versus placebo

Time to first event of CV death, nonfatal MI, or non-fatal strokeCompleted; patients at high risk 

for CV events on empagliflozin 

had a lower rate of the primary 

composite CV outcome and of 

death from any cause compared 

to placebo

Abbreviations: CANVAS: Canagliflozin Cardiovascular Assessment Study; CV: cardiovascular; DECLARE-TIMI: Dapagliflozin Effect 

on Cardiovascular Events; EMPA-REG OUTCOME: Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus 

Patients; MI: myocardial infarction; SGLT2: sodium glucose co-transporter-2 

VIII.Knowledge Gaps and Recommended Research

During the course of guideline development, the Work Group identified important areas for future 

research to assist in the next DM CPG update.

Evidence shows that DSME is effective but most reviews called for further research by way of welldesigned longitudinal studies. Research on comparative effectiveness of in-person versus technologybased education is needed. Investigation of effective modalities of DSME to provide education in areas 

where an educator is not available is also of interest. 

Three major intensive control studies of target HbA1c were designed to evaluate cardiovascular 

outcomes (ACCORD [56], VADT [57], and ADVANCE [58]). Newer therapeutic options have been 

introduced since these major trials were completed, and further research is needed to understand the 

effects of intensive control with newer therapies on macrovascular disease outcomes.

Further research is also required to determine whether HbA1c varies with racial/ethnic differences 

depending on the level of glycemic control, their clinical significance, and most importantly, implications 

for therapy. 

More research is required to determine the best measures of HbA1c variability and practical means to 

communicate them, whether or not there is a dose-response relationship for magnitude of variability or 

exposure to variability and, most importantly, whether interventions to reduce HbA1c variability affect 

outcomes.

There is a gap in research studies on therapeutic lifestyle counseling for all patients with T2DM that 

address sustainability over the long-term (greater than five years) and effective methods to implement 

interventions.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 66 of 160

Although a Mediterranean diet has been shown to improve glycemic control, weight, and cardiovascular 

outcomes in patients with T2DM, more research is needed to evaluate the effects and availability of the 

diet in the U.S. population, particularly in the VA and DoD populations. The VA/DoD population presents 

unique challenges regarding feasibility and acceptability of diet and lifestyle changes. Further research 

to determine new strategies that maximize adherence is needed for this population. Research is also 

needed to study the long-term effects of dietary modifications and specifically the implementation of a 

low glycemic index diet outside of the research setting. This CPG does not address MNT in conjunction 

with pharmacotherapy due to lack of evidence. Research comparing initiating nutrition therapy as a 

first-line therapy versus pharmacotherapy is needed.

Advancement in glucose monitoring technologies such as CGMs may improve the capability to safely 

target lower glucose levels, however, performance of these devices in acutely ill hospitalized patients is 

not well studied. Another practice that requires more study is the application of before-bed correction 

insulin for non-ICU hospitalized patients with T2DM. 

There are significant gaps in the evidence to support recommendations for inpatient diabetes education. 

There is inadequate evidence to assess which patients might benefit most from inpatient DM education 

and there are no high quality studies that have assessed for patient harms. 

Further research is required to determine the effectiveness of patient/lay person sensation testing as 

part of foot care self-management and if this increase in patient engagement decreases the frequency 

of poor foot outcomes. More studies are required to better compare outcomes of patients with limbthreatening conditions being seen by specialists versus primary care providers for non-urgent 

conditions, such as ingrown toenails.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 67 of 160

Appendix A: Evidence Review Methodology

A. Developing the Scope and Key Questions

The Champions, along with the Work Group, were tasked with identifying KQs to guide the systematic 

review of the literature on DM. These questions, which were developed in consultation with the Lewin 

team, addressed clinical topics of the highest priority for the VA and DoD populations. The KQs follow 

the population, intervention, comparison, outcome, timing and setting (PICOTS) framework for evidence 

questions, as established by the AHRQ. Table A-1 provides a brief overview of the PICOTS typology.

Table A-1. PICOTS [177] 

P 

Patients, 

Population, or 

Problem

A description of the patients of interest. It includes the condition(s), populations or subpopulations, disease severity or stage, co-occurring conditions, and other patient 

characteristics or demographics.

I Intervention or 

Exposure

Refers to the specific treatments or approaches used with the patient or population. It 

includes doses, frequency, methods of administering treatments, etc.

C Comparison

Describes the interventions or care that is being compared with the intervention(s) of 

interest described above. It includes alternatives such as placebo, drugs, surgery, lifestyle 

changes, standard of care, etc.

O Outcome

Describes the specific results of interest. Outcomes can include short, intermediate, and 

long-term outcomes, or specific results such as quality of life, complications, mortality, 

morbidity, etc.

(T) Timing, if 

applicable

Describes the duration of time that is of interest for the particular patient intervention 

and outcome, benefit, or harm to occur (or not occur).

(S) Setting, if 

applicable

Describes the setting or context of interest. Setting can be a location (such as primary, 

specialty, or inpatient care).

The Champions, Work Group, and evidence review team carried out several iterations of this process, 

each time narrowing the scope of the CPG and the literature review by prioritizing the topics of interest. 

Due to resource constraints, all developed KQs could not be included in the systematic evidence review. 

Thus, the Champions and Work Group determined which questions were of highest priority and those 

were included in the review. Table A-5 contains the final set of KQs used to guide the systematic 

evidence review for this CPG. 

a. Population(s)

• Adults 18 years or older with T2DM treated in any VA/DoD primary care setting

• The KQs are specific to adults 18 years or older with T2DM treated in any VA/DoD primary care

setting.

• KQ specific populations

 KQ1: Middle-aged individuals with approximate average age of 60 years

(Range: 40–75 years)

 KQ2: Adult patients with T2DM and comorbid medical conditions such as cancer, CKD 

and diabetes, and other end stage conditions or patients with multiple comorbidities

 KQ4a, KQ4b: Hospitalized adult patients with T2DM, excluding ICU settings

 KQ7: Patients with T2DM and attention also given to subpopulations: 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 68 of 160

• African American patients

• Elderly (>65 years)

• Patients with CKD, including end-stage renal disease

 KQ8: Patients with T2DM and attention given to women contemplating pregnancy if 

available

b. Interventions

Table A-2 below lists the interventions that are covered in this SR. The interventions are listed according to 

the key questions they address. 

Table A-2: Interventions 

Key 

Question Intervention(s)

1 Intensive glycemic control strategies—as defined by the study

2 Shared decision making strategies

3 Telehealth: 

 Real-time communication

 Asynchronous communication

 Non-face-to-face communication

 Face-to-face communication

e.g., mobile health, applications include self-directed versus guided, text messaging (SMS)

4a Basal-bolus plus correction type insulin protocol, basal plus (or anything with basal-bolus)

4b Managing glucose to 180 mg/dL

5 One or more of diabetes planning, management, and education interventions given at discharge or 

within certain period after discharge (e.g., phone calls, diabetes education, face-to-face visits, case 

management)

6 Higher long-term glucose variability (as defined by authors)

7 Patient characteristics that could affect test performances, such as ethnicity, race, older age, and CKD

8 Nutrition intervention strategies reviewed 

include:

Interventions include: 

 Low carbohydrate

 Low energy/low calorie

 Low fat

 Low glycemic index

 Medical nutrition therapy

 Carbohydrate counting

 Vegan

 Ketogenic

 Mediterranean

 Paleolithic

9 Interventions (e.g., online, technological including mobile apps, in-person including group and 

individual) designed to educate and support patients in self-management of diabetes

c. Comparators

Table A-3 lists the comparators of interest to this SR. The comparators are listed by the key question 

they address. 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 69 of 160

Table A-3: Comparators

Key 

Question Comparator(s)

1 Standard glycemic control strategies

2 Standard patient management

3 Standard patient management

4a Sliding scale insulin protocol, as well as the interventions outlined in Table A-2 (compare all three 

with each other)

4b Managing glucose to 200 mg/dL

5 Absence of diabetes planning, management and education interventions given at discharge or 

within certain period after discharge

6 Lower long-term glucose variability (as defined by authors)

7 Patient characteristics not present

8 No MNT, one or more of the diets listed as interventions in Table A-2

9 Standard of care

d. Outcomes

Table A-4 lists the outcomes of interest to this SR. The outcomes are listed by the key question they 

address.

Table A-4: Outcomes

Key 

Question Outcomes(s)

1  Hypoglycemia

 Diabetes-related microvascular complications

• Diabetic nephropathy

• Diabetic retinopathy

• Neuropathy

 Mortality

 Quality of life

 Cardiovascular outcomes

• Congestive heart failure

• Coronary artery disease

• Stroke

• MI

2  Patient psychosocial coping (e.g., 17-item Diabetes-related Distress Scale)

 Adherence to medication management, other behavioral change (e.g., missing scheduled

appointments or referrals)

 Measures of decisional conflict/discordance

• Decisional Conflict Scale

 Standard diabetes outcomes (see list for KQ1, above)

3  Adherence to regimen (pharmaceutical, behavioral)

 Standard diabetes outcomes (see list for KQ1, above)
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 70 of 160

Key 

Question Outcomes(s)

4a  Glucose variability

 Hypoglycemia 

 Hyperglycemia

 Length of stay

 Mortality

 30-day readmission 

 Provider satisfaction

4b  Hypoglycemia

 Dehydration

 Infection

 Length of stay

5  HbA1c

 Length of stay

 30-day readmission

 Patient psychosocial coping (e.g., 17-item Diabetes-related Distress Scale)

 Urgent care/emergency room visits

6  Microvascular outcomes (nephropathy, retinopathy, neuropathy)

 Acute coronary events (e.g., MI, unstable angina)

 Peripheral vascular disease

 Stroke

7 For different tests (HbA1c, eAG, fructosamine, glycated albumin, 1,5-anhydroglucitol, and/or 

continuous glucose monitoring): 

 Measurements of blood glycemic control including: fasting glucose, oral glucose tolerance test, 

2-hour post-prandial test

 Report on standard measurement of diagnostic test performance, if available, including: 

sensitivity, specificity, positive predictive value, negative predictive value

 Patient-centered outcomes will be captured if available

8  HbA1c

 Adherence to diet

 Blood pressure

 Dyslipidemia

 Hypoglycemia

 Hyperglycemia

 Weight change

 If information is available on progression to first use of pharmacotherapy

9  HbA1c

 Hypoglycemia

 Patient satisfaction/coping

 Diabetes self-efficacy (e.g., confidence)

e. Timing

Twelve weeks for studies looking at outpatient populations (except KQ 8 and 9); for KQ 8 and 9 the 

minimum follow-up was six months. For studies looking at inpatients (KQs 4a and 4b), follow-up is during 

hospital stay and 30-days post-discharge.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 71 of 160

f. Setting(s)

KQ 1-3, 6-9: Primary care; KQ 4, 5: Inpatient care

B. Conducting the Systematic Review

Extensive literature searches using the search terms and strategy included in Appendix H identified 5,012 

citations potentially addressing the KQs of interest to this evidence review. Of those, 1,940 were excluded 

upon title review for clearly not meeting inclusion criteria (e.g., not pertinent to the topic, not published in 

English, published prior to study inclusion publication date, not a full-length article). Overall, 3,072 

abstracts were reviewed with 2,328 of those being excluded for the following reasons: not an SR or clinical 

study, did not address a KQ of interest to this review, did not enroll a population of interest, or published 

prior to January 1, 2009. A total of 744 full-length articles were reviewed. Of those, 453 were excluded at a 

first-pass review for the following: not addressing a key question of interest, not enrolling the population 

of interest, not meeting inclusion criteria for clinical study or SR, not meeting inclusion criteria for any key 

question, or being a duplicate. A total of 291 full-length articles were thought to address one or more key 

questions and were further reviewed. Of these, 233 were ultimately excluded. Reasons for their exclusion 

are presented in Figure A-1 below. 

Overall, 58 studies addressed one or more of the KQs and were considered as evidence in this review. 

Table A-5 indicates the number of studies that addressed each of the questions. 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 72 of 160

Figure A-1. Study Flow Diagram

, 

 233 Citations Excluded at 2nd Pass Full Article Level

74 Wrong study design or does not address a KQ

72 Wrong study population or patients with T2DM 

not reported separately

63 SR superseded by more comprehensive review or 

relevant studies included in report

13 No outcomes of interest or comparator not of 

interest

11 Other (e.g. duplicate, published prior to 2009, not 

a clinical trial or SR)

 233 Citations Excluded at 2nd Pass Full Article Level

74 Wrong study design or does not address a KQ

72 Wrong study population or patients with T2DM 

not reported separately

63 SR superseded by more comprehensive review or 

relevant studies included in report

13 No outcomes of interest or comparator not of 

interest

11 Other (e.g. duplicate, published prior to 2009, not 

a clinical trial or SR)

1,940 Citations Excluded at the Title Level

Citations excluded at this level were off-topic, not 

published in English, or published prior to

inclusion date

1,940 Citations Excluded at the Title Level

Citations excluded at this level were off-topic, not 

published in English, or published prior to

inclusion date

5,012 Citations Identified by Searches

3,072 Abstracts 

Reviewed

3,072 Abstracts 

Reviewed

2,328 Citations Excluded at the Abstract Level

Citations excluded at this level were not SR or CS, 

clearly did not address a KQ, did not report on an 

outcome of interest, or were outside cutoff 

publication dates

2,328 Citations Excluded at the Abstract Level

Citations excluded at this level were not SR or CS, 

clearly did not address a KQ, did not report on an 

outcome of interest, or were outside cutoff 

publication dates

291 Articles 

Reviewed

58 Included Studies

 453 Citations Excluded at 1st Pass Full Article Level

Articles excluded at this level did not: address a key 

question of interest, enroll the population of interest, 

meet inclusion criteria for clinical study or systematic 

review, meet inclusion criteria for any key question, 

or were a duplicate.

 453 Citations Excluded at 1st Pass Full Article Level

Articles excluded at this level did not: address a key 

question of interest, enroll the population of interest, 

meet inclusion criteria for clinical study or systematic 

review, meet inclusion criteria for any key question, 

or were a duplicate.

744 Full-length Articles Reviewed
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 73 of 160

Table A-5. Evidence Base for Key Questions 

Question 

Number Question

Number of Studies and 

Type of Studies

1 In late middle-aged individuals (approximate average age of 60 years, 

typically in the range of 40–75 years) with T2DM, what are the benefits 

and harms of intensive glycemic control strategies relative to standard 

glycemic control strategies?

3 SRs

3 follow-up reports of RCTs

1 sub-study of an RCT

2 In patients with T2DM, is shared decision-making more effective than 

standard patient management in improving healthcare outcomes?

2 RCTs

3 In patients with T2DM, what is the comparative effectiveness of 

telehealth requiring physician interaction versus standard patient 

management in improving T2DM-related outcomes?

5 RCTs

4 a. In hospitalized patients with T2DM, excluding ICU settings, what is the

comparative effectiveness of a basal-bolus plus correction insulin

protocol and a sliding scale only insulin protocol for managing diabetes?

5 open-label RCTs

b. In hospitalized patients with T2DM, excluding ICU settings, what is the

comparative effectiveness of managing glucose to a goal of 180 mg/dL

versus 200 mg/dL on hospital and short-term post-discharge outcomes?

No studies identified

5 In adult inpatients with T2DM, what components of diabetes care 

management (excluding glycemic control) during the inpatient or 

immediately post-discharge period are associated with improved 

outcomes? Are some bundled components more effective than others?

2 RCTs

6 Among patients with T2DM, does increased long-term glucose variability 

affect the severity of microvascular and macrovascular outcomes?

1 SR

7 What are the differences among individuals from different ethnicities, 

age groups, any comorbid conditions in how biomarkers, such as HbA1c, 

eAG, and other biomarkers reflect glycemic control in the previous 

weeks / months? Is the correlation consistent across the range of values 

for the biomarkers or is it non-linear?

11 observational studies

8 In adults with T2DM, what is the safety and effectiveness of medical 

nutrition therapy as monotherapy or in conjunction with 

pharmacotherapy in controlling HbA1c and glycemic oscillations?

5 SRs

10 RCTs

9 In adults with T2DM, what is the effectiveness of diabetes selfmanagement education and support in controlling HbA1c in glycemia 

management and glycemic oscillations?

3 SRs

1 network meta-analysis 

6 RCTs

Total Evidence Base 58 Studies

a. Criteria for Study Inclusion/Exclusion

i. General Criteria

 Clinical studies or SRs published on or after January 1, 2009 to March 25, 2016, except for 

KQ7 (see Key Question Specific Criteria below.) If multiple SRs address a key question, we 

selected the most recent and/or comprehensive review. SRs were supplemented with 

clinical studies published subsequent to the SR.

 Studies must be published in English.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 74 of 160

 Publication must be a full clinical study or SR; abstracts alone were not included. Similarly, 

letters, editorials, and other publications that are not full-length clinical studies were not 

accepted as evidence. 

 Intervention studies had a treatment or management style and were a prospective, 

randomized controlled trial with an independent control group, unless otherwise noted (see 

Key Question Specific Criteria below). The ideal diagnostic study compares clinical outcomes 

after diagnostic technology evaluation versus clinical evaluation, or compares clinical 

outcomes linked to different diagnostic technologies. Non-comparative diagnostic studies 

reporting only characteristics of the diagnostic test (e.g., sensitivity, specificity, 

repeatability) were excluded. However, non-comparative diagnostic studies that report a 

change in management strategy or patient outcomes (e.g., evidence of organic based 

disease patterns) were considered.

 Study must have enrolled at least 20 patients (10 per study group) unless otherwise noted. 

(see Key Question Specific Criteria below.)

 Study must have reported on an outcome of interest. Study must have enrolled a patient 

population in which at least 80% of patients had a diagnosis of T2DM. If the percentage is 

less than 80%, then data must have been reported separately for this patient subgroup.

ii. Key Question Specific Criteria

 For KQ 1, acceptable study designs included SRs, RCTs, including follow-up studies of RCTs, 

cohorts and pre-planned, prospective analyses of those studies. Retrospective analyses 

were not included.

 For KQs 2-4, 8, and 9, acceptable study designs included SRs of RCTs and/or individual RCTs. 

 For KQ 5, acceptable study designs included SRs of acceptable study designs, individual 

RCTs or prospective nonrandomized controlled studies.

 For KQ 6, acceptable study designs included SRs of acceptable study designs, RCTs or 

prospective cohort studies that statistically compared outcomes for patients with T2DM and 

higher versus lower glucose variability. Large retrospective studies (200 patients minimum) 

that performed multivariate statistical analyses of the effect of higher and lower glucose 

variability on patient outcomes were also acceptable.

 For KQ7, it was determined after initial searches that the KQ required additional refinement 

and updated searches. Searches were updated to capture clinical studies or SRs published 

on or after January 1, 2009 to June 14, 2016.

 For KQ7, acceptable study designs included SRs, prospective blinded trials, cohort, or casecontrol studies comparing diabetes management metrics to HbA1c. For assessment of 

diagnostic accuracy, diagnostic cohort studies that compare a diagnostic test(s) to a 

reference standard (HbA1c) within the same patient were acceptable.

 For KQ9, trials set outside of the U.S. were considered to be out of scope, as the potential 

differences in education, support, cultural norms, and socioeconomic setting could 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 75 of 160

potentially limit applicability. Additionally, the minimum sample size per treatment arm was 

50 patients.

b. Literature Search Strategy

Information regarding the bibliographic databases, date limits, and platform/provider can be found in 

Table A-6, below. Additional information on the search strategies, including topic-specific search terms 

and search strategies can be found in Appendix H. 

Table A-6. Bibliographic Database Information

Name Date Limits Platform/Provider

Bibliographic Databases 

The Cochrane Central Register of Controlled Trials 

(CENTRAL) 1/1/2009-4/11/16 Wiley

The Cochrane Database of Methodology Reviews 

(Methodology Reviews) 1/1/2009-4/11/16 Wiley

The Cochrane Database of Systematic Reviews 

(Cochrane Reviews) 1/1/2009-4/11/16 Wiley

Database of Abstracts of Reviews of Effects 1/1/2009-4/11/16 Wiley

EMBASE (Excerpta Medica) 1/1/2009-4/4/16

KQ7 1/1/2009-6/14/16 Elsevier

Health Technology Assessment Database (HTA) 1/1/2009-4/11/16 Wiley

MEDLINE/PreMEDLINE 1/1/2009-4/4/16

KQ7 1/1/2009-6/14/16 OVIDSP

PubMed (In-process and Publisher records) 1/1/2009-4/4/16

KQ7 1/1/2009-6/14/16

NLM

Gray Literature Resources 

AHRQ 1/1/2009-4/11/16 AHRQ

Healthcare Standards database 1/1/2009-4/11/16 ECRI Institute

National Guideline ClearinghouseTM 1/1/2009-4/11/16 AHRQ

National Institute of Health and Clinical Excellence 1/1/2009-4/11/16 NHS

C. Convening the Face-to-face Meeting

In consultation with the contracting officer's representative, the Champions, and the Work Group, the 

Lewin Team convened a three and a half day face-to-face meeting of the Champions and Work Group 

members on June 21-24, 2016. These experts were gathered to develop and draft the clinical 

recommendations for an update to the 2010 DM CPG. Lewin presented findings from the evidence 

review of KQs 1-9 in order to facilitate and inform the process. 

Under the direction of the Champions, the Work Group members were charged with interpreting the 

results of the evidence review, and asked to categorize and carry forward recommendations from the 

2010 DM CPG, modifying the recommendations as necessary. The members also developed new clinical 

practice recommendations not presented in the 2010 DM CPG, based on the 2016 evidence review. The 

subject matter experts were divided into three smaller subgroups at this meeting. 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 76 of 160

As the Work Group members drafted clinical practice recommendations, they also assigned a grade for 

each recommendation based on a modified GRADE and USPSTF methodology. Each recommendation 

was graded by assessing the quality of the overall evidence base, the associated benefits and harms, the 

variation in values and preferences, and other implications of the recommendation.

In addition to developing recommendations during the face-to-face meeting, the Work Group members 

also revised the 2010 DM CPG algorithms to reflect the new and amended recommendations. They 

discussed the available evidence as well as changes in clinical practice since 2010, as necessary, to 

update the algorithms.

D. Grading Recommendations

This CPG uses the GRADE methodology to assess the quality of the evidence base and assign a grade for 

the strength for each recommendation. The GRADE system uses the following four domains to assess 

the strength of each recommendation:[15] 

• Balance of desirable and undesirable outcomes

• Confidence in the quality of the evidence

• Values and preferences

• Other implications, as appropriate, e.g.,:

 Resource use

 Equity

 Acceptability

 Feasibility

 Subgroup considerations

The following sections further describe each domain. 

Balance of desirable and undesirable outcomes refers to the size of anticipated benefits (e.g., increased 

longevity, reduction in morbid event, resolution of symptoms, improved QoL, decreased resource use) and 

harms (e.g., decreased longevity, immediate serious complications, adverse event, impaired quality of life, 

increased resource use, inconvenience/hassle) relative to each other. This domain is based on the 

understanding that the majority of clinicians will offer patients therapeutic or preventive measures as long 

as the advantages of the intervention exceed the risks and adverse effects. The certainty or uncertainty of 

the clinician about the risk-benefit balance will greatly influence the strength of the recommendation.

Some of the discussion questions that fall under this domain include:

• Given the best estimate of typical values and preferences, are you confident that the benefits

outweigh the harms and burden or vice versa?

• Are the desirable anticipated effects large?

• Are the undesirable anticipated effects small?

• Are the desirable effects large relative to undesirable effects?
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 77 of 160

Confidence in the quality of the evidence reflects the quality of the evidence base and the certainty in 

that evidence. This second domain reflects the methodological quality of the studies for each outcome 

variable. In general, the strength of recommendation follows the level of evidence, but not always, as 

other domains may increase or decrease the strength. The evidence review used for the development of 

recommendations for DM, conducted by ECRI, assessed the confidence in the quality of the evidence 

base and assigned a rating of “High,” “Moderate,” “Low,” or “Very Low.” 

The elements that go into the confidence in the quality of the evidence include: 

• Is there high or moderate quality evidence that answers this question?

• What is the overall certainty of this evidence?

Values and preferences is an overarching term that includes patients’ perspectives, beliefs, 

expectations, and goals for health and life. More precisely, it refers to the processes that individuals use 

in considering the potential benefits, harms, costs, limitations, and inconvenience of the therapeutic or 

preventive measures in relation to one another. For some, the term “values” has the closest 

connotation to these processes. For others, the connotation of “preferences” best captures the notion 

of choice. In general, values and preferences increase the strength of the recommendation when there 

is high concordance and decrease it when there is great variability. In a situation in which the balance of 

benefits and risks are uncertain, eliciting the values and preferences of patients and empowering them 

and their surrogates to make decisions consistent with their goals of care becomes even more 

important. A recommendation can be described as having “similar values,” “some variation,” or “large 

variation” in typical values and preferences between patients and the larger populations of interest.

Some of the discussion questions that fall under the purview of values and preferences include:

• Are you confident about the typical values and preferences and are they similar across the 

target population?

• What are the patient’s values and preferences? 

• Are the assumed or identified relative values similar across the target population?

Other implications consider the practicality of the recommendation, including resource use, equity, 

acceptability, feasibility, and subgroup considerations. Resource use is related to the uncertainty around 

the cost-effectiveness of a therapeutic or preventive measure. For example statin use in the frail elderly 

and others with multiple co-occurring conditions may not be effective and, depending on the societal 

benchmark for willingness to pay, may not be a good use of resources. Equity, acceptability, feasibility,

and subgroup considerations require similar judgments around the practically of the recommendation.

The framework below was used by the Work Group to guide discussions on each domain.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 78 of 160

Table A-7. Evidence to Recommendation Framework

Decision Domain Judgment

Balance of desirable and undesirable outcomes

 Given the best estimate of typical values and preferences, are you

confident that the benefits outweigh the harms and burden or vice

versa?

 Are the desirable anticipated effects large?

 Are the undesirable anticipated effects small?

 Are the desirable effects large relative to undesirable effects?

 Benefits outweigh harms/ burden

 Benefits slightly outweigh

harms/burden

 Benefits and harms/burden are

balanced

 Harms/burden slightly outweigh

benefits

 Harms/burden outweigh benefits

Confidence in the quality of the evidence

 Is there high or moderate quality evidence that answers this question?

 What is the overall certainty of this evidence?

 High

 Moderate

 Low

 Very low

Values and preferences

 Are you confident about the typical values and preferences and are

they similar across the target population?

 What are the patient’s values and preferences?

 Are the assumed or identified relative values similar across the target

population?

 Similar values

 Some variation

 Large variation

Other implications (e.g., resource use, equity, acceptability, feasibility, subgroup considerations)

 Are the resources worth the expected net benefit from the

recommendation?

 What are the costs per resource unit?

 Is this intervention generally available?

 Is this intervention and its effects worth withdrawing or not allocating

resources from other interventions?

 Is there lots of variability in resource requirements across settings?

 Various considerations

The strength of a recommendation is defined as the extent to which one can be confident that the 

desirable effects of an intervention outweigh its undesirable effects and is based on the framework 

above, which combines the four domains.[15] GRADE methodology does not allow for 

recommendations to be made based on expert opinion alone. While strong recommendations are 

usually based on high or moderate confidence in the estimates of effect (quality of the evidence) there 

may be instances where strong recommendations are warranted even when the quality of evidence is 

low.[178] In these types of instances where the balance of desirable and undesirable outcomes and 

values and preferences played large roles in determining the strength of a recommendation, this is 

explained in the discussion section for the recommendation.

The GRADE of a recommendation is based on the following elements:

• Four decision domains used to determine the strength and direction (described above)

• Relative strength (Strong or Weak)

• Direction (For or Against)
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 79 of 160

The relative strength of the recommendation is based on a binary scale, “Strong” or “Weak.” A strong 

recommendation indicates that the Work Group is highly confident that desirable outcomes outweigh 

undesirable outcomes. If the Work Group is less confident of the balance between desirable and 

undesirable outcomes, they present a weak recommendation.

Similarly, a recommendation for a therapy or preventive measure indicates that the desirable 

consequences outweigh the undesirable consequences. A recommendation against a therapy or 

preventive measure indicates that the undesirable consequences outweigh the desirable consequences.

Using these elements, the grade of each recommendation is presented as part of a continuum:

• Strong For (or “We recommend offering this option ...”)

• Weak For (or “We suggest offering this option ...”)

• Weak Against (or “We suggest not offering this option ...”)

• Strong Against (or “We recommend against offering this option ...”)

Note that weak (For or Against) recommendations may also be termed “Conditional,” “Discretionary,” or 

“Qualified.” Recommendations may be conditional based upon patient values and preferences, the 

resources available, or the setting in which the intervention will be implemented. Recommendations 

may be at the discretion of the patient and clinician or they may be qualified with an explanation about 

the issues that would lead decisions to vary.

E. Recommendation Categorization

a. Recommendation Categories and Definitions

For use in the 2017 DM CPG, a set of recommendation categories was adapted from those used by the 

United Kingdom National Institute for Health and Clinical Excellence.[18,19] These categories, along with 

their corresponding definitions, were used to account for the various ways in which recommendations 

could have been updated from the 2010 DM CPG. The categories and definitions can be found in 

Table A-8.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 80 of 160

Table A-8. Recommendation Categories and Definitions 

Evidence 

Reviewed*

Recommendation 

Category* Definition*

Reviewed

New-added New recommendation following review of the evidence

New-replaced Recommendation from previous CPG that has been carried over to the 

updated CPG that has been changed following review of the evidence

Not changed

Recommendation from previous CPG that has been carried forward to the 

updated CPG where the evidence has been reviewed but the 

recommendation is not changed

Amended

Recommendation from the previous CPG that has been carried forward to 

the updated CPG where the evidence has been reviewed and a minor 

amendment has been made

Deleted Recommendation from the previous CPG that has been removed based on 

review of the evidence

Not reviewed

Not changed Recommendation from previous CPG that has been carried forward to the 

updated CPG, but for which the evidence has not been reviewed

Amended

Recommendation from the previous CPG that has been carried forward to 

the updated CPG where the evidence has not been reviewed and a minor 

amendment has been made

Deleted Recommendation from the previous CPG that has been removed because it 

was deemed out of scope for the updated CPG

*Adapted from the NICE guideline manual (2012) [18] and Garcia et al. (2014) [19]

Abbreviation: CPG: clinical practice guideline

b. Categorizing Recommendations with an Updated Review of the Evidence

Recommendations were first categorized by whether or not they were based on an updated review of 

the evidence. If evidence had been reviewed, recommendations were categorized as “New-added,” 

“New-replaced,” “Not changed,” “Amended,” or “Deleted.” 

“Reviewed, New-added” recommendations were original, new recommendations that were not in the 

2010 DM CPG. “Reviewed, New-replaced” recommendations were in the previous version of the 

guideline, but were modified to align with the updated review of the evidence. These recommendations 

could have also included clinically significant changes to the previous version. Recommendations 

categorized as “Reviewed, Not changed” were carried forward from the previous version of the CPG 

unchanged. 

To maintain consistency between 2010 recommendations, which were developed using the USPSTF 

methodology, and 2017 recommendations, which were developed using the GRADE methodology, it was 

necessary to modify the 2010 recommendations to include verbiage to signify the strength of the 

recommendation (e.g., “We recommend,” “We suggest”). Because the 2010 recommendations 

inherently needed to be modified at least slightly to include this language, the “Not changed” category 

was not used. For recommendations carried forward to the updated CPG with review of the evidence 

and slightly modified wording, the “Reviewed, Amended” recommendation category was used. This 

allowed for the wording of the recommendation to reflect GRADE methodology as well as for any other 

non-substantive (i.e., not clinically meaningful) language changes deemed necessary. The evidence used 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 81 of 160

to support these recommendations was carried forward from the previous version of the CPG and/or 

was identified in the evidence review for the update. 

Recommendations could have also been designated “Reviewed, Deleted.” These were

recommendations from the previous version of the CPG that were not brought forward to the updated 

guideline after review of the evidence. This occurred if the evidence supporting the recommendations 

was out of date, to the extent that there was no longer any basis to recommend a particular course of 

care and/or new evidence suggests a shift in care, rendering recommendations in the previous version 

of the guideline obsolete.

c. Categorizing Recommendations without an Updated Review of the Evidence

There were also cases in which it was necessary to carry forward recommendations from the previous 

version of the CPG without a SR of the evidence. Due to time and budget constraints, the update of the 

DM CPG could not review all available evidence on management of DM, but instead focused its KQs on 

areas of new or updated scientific research or areas that were not previously covered in the CPG. 

For areas of research that have not changed, and for which recommendations made in the previous 

version of the guideline were still relevant, recommendations could have been carried forward to the 

updated guideline without an updated SR of the evidence. The support for these recommendations in 

the updated CPG was thus also carried forward from the previous version of the CPG. These 

recommendations were categorized as “Not reviewed.” If evidence had not been reviewed, 

recommendations could have been categorized as “Not changed,” Amended,” or “Deleted.” 

“Not reviewed, Not changed” recommendations refer to recommendations from the previous version of 

the DM CPG that were carried forward unchanged to the updated version. The category of “Not 

reviewed, Amended” was used to designate recommendations which were modified from the 2010 CPG 

with the updated GRADE language, as explained above. 

Recommendations could also have been categorized as “Not reviewed, Deleted” if they were 

determined to be out of scope. A recommendation was out of scope if it pertained to a topic (e.g., 

population, care setting, treatment, condition) outside of the scope for the updated CPG as defined by 

the Work Group. 

The categories for the recommendations included in the 2017 version of the guideline are noted in the 

Recommendations. Recommendations 6, 9, 10, 12, 15, 17, 19, 20, 21, 22, 23, and 24 were carried 

forward from the 2010 DM CPG using this method. The categories for the recommendations from the 

2010 DM CPG are noted in Appendix F.

F. Drafting and Submitting the Final Clinical Practice Guideline

Following the face-to-face meeting, the Champions and Work Group members were given writing 

assignments to craft discussion sections to support each of the new recommendations and/or to update 

discussion sections from the 2010 DM CPG to support the amended “carried forward” 

recommendations. The Work Group also considered tables, appendices, and other sections from the 

2010 DM CPG for inclusion in the update. During this time, the Champions and Work Group also made 

additional revisions to the algorithms, as necessary. 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 82 of 160 

After developing the initial draft of the updated CPG, an iterative review process was used to solicit 

feedback on and make revisions to the CPG. Once they were developed, the first two drafts of the CPG 

were posted on a wiki website for a period of 14-20 business days for internal review and comment by 

the Work Group. All feedback submitted during each review period was reviewed and discussed by the 

Work Group and appropriate revisions were made to the CPG. 

Draft 3 of the CPG was made available for peer review and comment. This process is described in Peer 

Review Process. After revisions were made based on the feedback received during the peer review and 

comment period, the Champions presented the CPG to the EBPWG for their approval. Changes were 

made based on feedback from the EBPWG and the guideline was finalized. 

The Work Group also produced a set of guideline toolkit materials which included a provider summary, 

pocket cards, and a patient summary. The final 2017 DM CPG was submitted to the EBPWG in 

April 2017. 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 83 of 160

Appendix B: Pharmacotherapy 1 [139] 

A. Alpha-glucosidase inhibitors

Drug Class

Average 

HbA1c 

Reduction

Potential for 

Hypoglycemia

Impact 

on 

Weight Clinical Considerations

Adverse 

Events/Side Effects Cost

Acarbose

Miglitol

0.5 - 1% Low Weight 

neutral

 Administer at the start of each main meal

 Titrate dose gradually to minimize GI effects

 GI side effects may be intensified in patients

consuming large amounts of simple

carbohydrates

 Reduces postprandial glucose values

 Not recommended in patients with significant

renal impairment (SCr >2 mg/dL)

 Use with caution in hepatic impairment

 Contraindications: DKA, inflammatory bowel

disease, colonic ulceration, partial intestinal

obstruction, marked disorders of digestion or

absorption conditions, cirrhosis (acarbose)

 Prevents breakdown of table sugar; therefore,

a source of glucose (dextrose, D-glucose)

should be readily available to treat symptoms

of hypoglycemia

 Flatulence; tend to

abate with time

 Diarrhea and

abdominal pain

 Dose-related

increase in serum

transaminases,

usually

asymptomatic,

reversible

(acarbose)

 Inexpensive

(acarbose)

 Moderately

expensive

(miglitol)

Abbreviations: DKA: diabetic ketoacidosis; dL: deciliter; GI: gastrointestinal; HbA1c: hemoglobin A1c; mg: milligram; SCr: serum creatinine

1 Information is based on Work Group consensus, VA/DoD evidence-based reviews, and product package inserts. Average values shown; response is dependent on other factors 

such as whether drug therapy naïve, baseline HbA1c, concomitant anti-glycemic therapy, etc. Clinical considerations and adverse events/side effects are not intended to be 

inclusive of all information, but rather to highlight some of the key points. Refer to agency pricing sources for current cost information; lower pricing within a class may be 

available for agency preferred agents, or as new generics become available. 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 84 of 160

B. Amylin analog

Drug Class

Average 

HbA1c 

Reduction

Potential for 

Hypoglycemia

Impact on 

Weight Clinical Considerations

Adverse Events/Side 

Effects Cost

Pramlintide 0.5 - 1% High (especially 

in those with 

T1DM)

↓Weight  Indicated to be co-administered with mealtime

insulin

 Reduces postprandial glucose values

 Requires frequent pre- and post-meal and

bedtime glucose monitoring

 When initiating pramlintide, reduce mealtime

insulin (including premixed insulin) dose by 50%;

individualize subsequent insulin doses

thereafter

 Contraindicated in those with hypoglycemia

unawareness and confirmed gastroparesis

 Patients that should NOT be considered for

pramlintide therapy:

• Poor compliance with current insulin

regimen

• Poor compliance with prescribed SMBG

• HbA1c >9%

• Recurrent severe hypoglycemic requiring

assistance during the past 6 months

• Require the use of drugs that stimulate GI

motility

• pediatric patients

 Injectable

 GI effects (nausea,

vomiting, anorexia)

Expensive

Abbreviations: GI: gastrointestinal; HbA1c: hemoglobin A1c; SMBG: self-monitoring of blood glucose; T1DM: type 1 diabetes mellitus
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 85 of 160

C. Biguanides

Drug Class

Average 

HbA1c 

Reduction

Potential for 

Hypoglycemia

Impact on 

Weight Clinical Considerations

Adverse Events /Side 

Effects Cost

Metformin 1 - 1.5% Low Weight 

neutral

 Use well established

 Before starting metformin, obtain the

patient’s eGFR

 Metformin is contraindicated in patients

with an eGFR below 30 mL/min/1.73 m2

 Starting metformin in patients with an eGFR

between 30-45 mL/min/1.73 m2 is not

recommended

 Obtain an eGFR at least annually in all

patients taking metformin; in patients at

increased risk for the development of renal

impairment such as the elderly, renal

function should be assessed more

frequently

 In patients taking metformin whose eGFR

later falls below 45 mL/min/1.73 m2

, assess

the benefits and risks of continuing

treatment; discontinue metformin if the

patient’s eGFR later falls below 30

mL/min/1.73 m2

 Titrate dose gradually to minimize GI

symptoms; a trial of metformin extendedrelease should be offered to patients

experiencing continued GI effects

 Likely reduces CV events (UKPDS)

 GI effects (diarrhea,

nausea, abdominal

cramping)

 Rare risk of lactic

acidosis (risk is

increased in patients

with acute CHF,

dehydration, excessive

alcohol intake, renal

impairment or sepsis)

 May impair vitamin B12

absorption; rarely

associated with anemia

Inexpensive

Abbreviations: CHF: congestive heart failure; CV: cardiovascular; eGFR: estimated glomerular filtration rate; GI: gastrointestinal; HbA1c: hemoglobin A1c; m2: square meter; min: 

minute; mL: milliliter; UKPDS: United Kingdom Prospective Diabetes Study 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 86 of 160

D. Dipeptidyl-peptidase 4 inhibitors

Drug Class

Average 

HbA1c 

Reduction

Potential for 

Hypoglycemia

Impact 

on 

Weight Clinical Considerations Adverse Events/Side Effects Cost

Sitagliptin

Saxagliptin

Linagliptin

Alogliptin

0.5 - 1% Low 

(↑ risk when 

combined with

SU or insulin)

Weight 

neutral

 May require dosage

adjustment for renal

impairment or concomitant

use of strong CYP3A4/5

inhibitors (varies by product)

 Use of CYP3A4 or P-gp

inducers with linagliptin is

not recommended

 No cardiovascular benefits

compared to placebo

 Not studied in patients with

history of pancreatitis

 Hypersensitivity reactions (e.g., urticaria,

facial edema); post-marketing reports of

serious hypersensitivity reactions such as

anaphylaxis, angioedema, and exfoliative

skin conditions

 Acute pancreatitis has been reported;

discontinue if pancreatitis is suspected

 Severe and disabling arthralgia has been

reported

 May increase risk for hospitalization for

heart failure (saxagliptin and alogliptin)

Expensive

Abbreviations: CYP3A4/5: Cytochrome P450 3A4; HbA1c: hemoglobin A1c; P-gp: P-glycoprotein; SU: sulfonylurea
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 87 of 160

E. Glucagon-like 1 peptide receptor agonists

Drug Class

Average 

HbA1c 

Reduction

Potential for 

Hypoglycemia

Impact on 

Weight Clinical Considerations

Adverse Events/Side 

Effects Cost

Exenatide

Liraglutide

Lixisenatide

Once weekly 

agents

Exenatide

Albiglutide

Dulaglutide

1 - 1.5% Low 

(↑ risk when 

combined with

SU or insulin)

↓ Weight  Reduces postprandial glucose values

 Contraindicated in patients with a

personal or family history of

medullary thyroid carcinoma or in

patients with multiple endocrine

neoplasia syndrome type 2

 Consider other antidiabetic therapies

in patients with a history of

pancreatitis

 Use with caution in patients receiving

oral medications that require rapid GI

absorption

 Avoid use if patient has severe GI

disease, including severe

gastroparesis

 May require dosage adjustment for

renal impairment (varies by product);

exenatide should not be used if eGFR

<30 mL/minute/1.73 m2

 Injectable

 Liraglutide was shown to reduce the

risk of cardiovascular events

 GI effects (nausea,

vomiting, diarrhea)

 Reports of renal

impairment usually in

association with nausea,

vomiting, diarrhea

 Injection site reactions

 Post-marketing reports,

including fatal and nonfatal hemorrhagic or

necrotizing pancreatitis.

 Post-marketing reports

of serious

hypersensitivity reactions

(e.g., anaphylactic

reactions and

angioedema).

 Unconfirmed association

with medullary cell

carcinoma

Expensive

Abbreviations: CYP3A4/5: Cytochrome P450 3A4; eGFR: estimated glomerular filtration rate; GI: gastrointestinal; HbA1c: hemoglobin A1c; m2: square meter; mL: milliliter; SU: 

sulfonylurea
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 88 of 160

F. Insulin

Drug Class

Average 

HbA1c 

Reduction

Potential for 

Hypoglycemia

Impact on 

Weight Clinical Considerations

Adverse Events /

Side Effects Cost

Insulin (prandial)

Short-acting

Regular

Rapid-acting analog

Lispro 

Aspart

Glulisine

Insulin (basal)

Intermediate-acting

NPH

Long-acting analogs

Glargine

Detemir

Degludec

Premixed

NPH/Regular 

Biphasic insulin aspart 

Insulin lispro

protamine/lispro 

Insulin degludec/aspart

Variable Moderate-high ↑ Weight  Use well established

 Most effective at lowering

elevated glucose

 Dosing can be individualized

 Beneficial effect on

triglycerides and HDL-C

 Lower doses may be needed

for renal and hepatic

impairment

 Patient training needed

 Hypersensitivity

reactions

 Injection site

reactions

 Anaphylaxis has

been reported

(rare)

 Inexpensive

(human

insulin)

 Moderate to

expensive

(analogs)

Abbreviations: HbA1c: hemoglobin A1c; HDL-C: high-density lipoprotein cholesterol; NPH: neutral protamine Hagedorn
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 89 of 160

G. Meglitinides

Drug Class

Average 

HbA1c 

Reduction

Potential for 

Hypoglycemia

Impact on 

Weight Clinical Considerations

Adverse Events/Side 

Effects Cost

Nateglinide

Repaglinide

0.5 - 1% Moderate ↑ Weight  Administer with meals; scheduled dose

should not be administered if a meal is

missed to avoid hypoglycemia

 Reduces postprandial glucose values

 Use with caution in patients with

moderate to severe hepatic

impairment and severe renal

impairment

 Use with caution in the elderly,

debilitated, and malnourished patients;

may be more susceptible to glucoselowering effects

 Combination therapy with SU is not

recommended, no additional benefit

 Upper respiratory

infection

 Flu-like symptoms

 Inexpensive

(repaglinide)

 Moderately

expensive

(nateglinide)

Abbreviations: HbA1c: hemoglobin A1c; SU: sulfonylureas
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 90 of 160

H. Sodium glucose co-transporter 2 (SGLT2) inhibitors

Drug Class

Average 

HbA1c 

Reduction

Potential for 

Hypoglycemia

Impact on 

Weight Clinical Considerations Adverse Events/Side Effects Cost

Canagliflozin

Dapagliflozin

Empagliflozin

0.5 – 1% Low ↓ Weight  Do not use if eGFR <45 mL/min/1.73

m2 (empagliflozin/canagliflozin) or

<60 mL/min/1.73 m2 (dapagliflozin)

 Empagliflozin was shown to reduce

the risk of cardiovascular events

compared to placebo

 Decrease triglycerides

 Increase HDL-C

 Increase LDL-C

 Urinary tract

infections/urosepsis

 Genital mycotic infections

(higher incidence in females

and uncircumcised males)

 Increased risk for hypotension,

orthostasis, volume depletion

in elderly, those taking

diuretics, or antihypertensives

 Decreased eGFR or increased

serum creatinine may occur;

elderly and those with

preexisting renal impairment

may be at greater risk

 Decrease in systolic blood

pressure (~4-6 mmHg)

 DKA rare (presenting blood

glucose levels may be below

those typically expected for

diabetic ketoacidosis (often

<250 mg/dL).

 Decreased bone density and

increased risk of bone

fractures reported with

canagliflozin

Expensive

Abbreviations: DKA: diabetic ketoacidosis; dL: deciliter; eGFR: estimated glomerular filtration rate; HbA1c: hemoglobin A1c; HDL-C: high density lipoprotein-cholesterol; LDL-C: 

low density lipoprotein-cholesterol; m2:square meter; mg: milligram; min: minute; mL: milliliter; mmHg: millimeter of mercury
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 91 of 160

I. Sulfonylureas

Drug Class

Average 

HbA1c 

Reduction

Potential for 

Hypoglycemia

Impact on 

Weight Clinical Considerations

Adverse Events/Side 

Effects Cost

Second 

Generation

Glimepiride

Glipizide

Glyburide

First generation 

agents seldom 

used

Chlorpropamide 

Tolazamide 

Tolbutamide

1 -1.5% Moderate ↑ Weight  Effectiveness diminishes with

progression of T2DM due to continued

beta cell destruction

 Use with caution in elderly and patients

with hepatic or renal impairment

 Patients with G6PD may be at an

increased risk of SU-induced hemolytic

anemia

 Allergic skin reactions

 SIADH has been

reported

 Dose-related GI effects

(nausea, diarrhea,

constipation)

Inexpensive

Abbreviations: G6PD: glucose-6-phosphate dehydrogenase deficiency; GI: gastrointestinal; HbA1c: hemoglobin A1c; SIADH: syndrome of inappropriate antidiuretic hormone 

secretion; SU: sulfonylurea; T2DM: type 2 diabetes mellitus
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 92 of 160

J. Thiazolidinediones

Drug Class

Average 

HbA1c 

Reduction

Potential for 

Hypoglycemia

Impact on 

Weight Clinical Considerations

Adverse Events/Side 

Effects Cost

Pioglitazone

Rosiglitazone

1 – 1.5% Low 

(↑ risk when 

combined with

SU or insulin)

↑ Weight  Contraindicated in those with NYHA

Class III or IV heart failure

 Use with caution in patients with

NYHA Class I/II heart failure or

patients with risk factors for heart

failure

 Not recommended in symptomatic

heart failure

 Do not use in patients with active

bladder cancer; consider risk versus

benefits of using pioglitazone in those

with a history of bladder cancer

 Use with caution in premenopausal,

anovulatory women; may result in

resumption of ovulation, increasing

risk of pregnancy

 Administer cautiously in those with

abnormal liver function tests

 Pioglitazone may reduce CV events

 Edema usually doserelated

 Cause or exacerbate

heart failure (greater

risk if used with

insulin)

 Macular edema has

been reported (may

present with blurred

vision or decreased

visual acuity)

 Increased incidence

of bone fractures in

females occurring in

the upper arm, hand

and foot

 Liver injury has been

reported; if ALT >3x

ULN do not reinitiate

therapy without

another explanation

for the liver test

abnormalities

 Inexpensive

(pioglitazone)

 Moderately

expensive

(rosiglitazone)

Abbreviations: ALT: alanine aminotransferase; CV: cardiovascular; HbA1c: hemoglobin A1c; NYHA: New York Heart Association; SU: sulfonylurea; ULN: upper limit of normal
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 93 of 160

Appendix C: FDA Approved/ Studied Combination Therapy1,2 [139] 

AGIs

DPP-4

inhibitors

GLP-1 

agonists Insulin Meglitinides Metformin

SGLT2 

inhibitors SUs TZDs

AGIs N/A

DPP-4 

inhibitors N/A

GLP-1 

agonists * N/A

Insulin X X X† N/A

Meglitinides N/A

Metformin X X X X X N/A

SGLT2 

inhibitors X X X N/A

SUs X X X X X X N/A

TZDs X X X± X X X X N/A

Abbreviations: AGI: α-glucosidase; DPP4: dipeptidyl peptidase-4; GLP-1: glucagon-like peptide-1; SGLT2: sodium glucose cotransporter 2; SU: sulfonylurea; TZD: thiazolidinedione

1 Agents listed in alphabetical order

2This table reflects FDA approved indications and/or well-studied combinations. All combinations have not been studied at this 

time and evidence is rapidly evolving. 

*The data for GLP-1 agonists in combination with both basal and prandial insulin are very limited at this time.

†Exenatide once weekly + insulin is not recommended per product labeling.

±Rosiglitazone + insulin is not recommended per product labeling.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 94 of 160

Appendix D: Patient Focus Group Methods and Findings

A. Methods

On March 8, 2016, as part of the effort to update this CPG, the VA and DoD Leadership, along with the 

DM CPG Working Group, held a patient focus group at the VA Puget Sound Health Care System −

American Lake Division. The focus group was comprised of five patients. 

The aim of the focus group was to further the understanding of the perspective of patients receiving 

treatment for DM within the VA and/or DoD healthcare systems, as these patients are most affected by 

the recommendations put forth in the updated DM CPG. The focus group explored patient perspectives 

on a set of topics related to management of DM in the VA and DoD healthcare systems, including 

patients’ knowledge of DM treatments and alternate treatment options, views on the delivery of care, 

and the impact of DM on the patients and the challenges it poses.

Participants for the focus group were recruited by Eric Rodgers, Director of the Evidence-based Practice 

Program, Office of Quality, Safety and Value for the Department of Veterans Affairs, Corinne Devlin, 

Chief, Office of Evidence-Based Practice Clinical Performance Directorate, and by the DM CPG 

Champions. Patient focus group participants were not intended to be a representative sample of VA and 

DoD patients who have experienced DM. However, recruitment focused on eliciting a range of 

perspectives likely to be relevant and informative in the guideline development process. Patients were 

not incentivized for their participation or reimbursed for travel expenses.

The DM CPG Champions and Work Group developed a set of questions to help guide the focus group. 

The facilitator from Lewin led the discussion using interview questions prepared by the Work Group as a 

general guide to elicit the most important information from the patients regarding their experiences and 

views about their treatment and overall care. Given the limited time and the range of interests of the 

focus group participants, not all of the listed questions were addressed. 

At the time of the focus group, all five patients were receiving care in the VA healthcare system. Some of 

these patient participants had transitioned between multiple care settings, including from DoD to VA. 

The time since patients had been diagnosed with DM ranged from three weeks to 25 years at the time 

of the focus group. All patients had T2DM. Two patients stated that other members in their family had

DM as well. One patient stated he was currently on insulin pump therapy. 

The following concepts are aspects of care that are important to these patients, which emerged from 

the focus group discussion. Each of these themes was an important and needed aspect of participants’ 

healthcare. 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 95 of 160

B. Patient Focus Group Findings

a. Using shared decision-making, consider all treatment options and develop a

treatment plan based on the balance of risks, benefits, and patient-specific

goals, values, and preferences

• Use shared decision-making to develop an individualized treatment plan; discuss pros and cons

(e.g., benefits, risks, side effects) of each treatment option in conjunction with each patient’s

goals, priorities, values, and preferences.

• Periodically re-evaluate and reassess the patient’s medications as new drug formulations and

devices are available.

• Re-evaluation of the side effects and titration of the medicines are important during shared

decision-making.

• Discuss pharmacologic options in depth with the patient, including their willingness to take

medications and their preferences for other treatments.

b. Guide patients for the self-management of their diabetes and glucose

monitoring, including benefits and risks, and their expectations

• Guide and educate patients on the self-management of their diabetes.

• Educate patients on the reason for SMBG throughout the day.

• Consider the benefits, risks, and patients’ expectations during the self-management of their

diabetes.

c. Educate and involve family caregivers and co-workers in accordance with

patient preferences regarding core knowledge of diabetes management

• Foster family involvement in shared decision-making and patient support in accordance with

patient preferences and in a way that is beneficial to the patient.

• Educate and include family members early in treatment discussions, especially regarding core

knowledge on management of diabetes.

• Build and maintain trust, respect, and support with the patient and their family.

• Educate patients’ co-workers on the core knowledge on management of diabetes in accordance

with patient preference.

d. Within and between VA and DoD healthcare systems, work with appropriate

providers to ensure continuity of high-quality care and timely consult and/or

referral to an endocrinologist as appropriate

• Clinicians should listen actively and be responsive to each patient’s agenda during clinic visits.

• Provide seamless transitions in DM treatment within and between VA, DoD, and other

healthcare systems; patients should not have to encounter delays in diagnosis of DM, changes in

treatment regimens, or have to “start all over” when moving to another provider.

• Provide timely consult and/or referrals to endocrinologists as appropriate.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 96 of 160

e. Create a support system for patients with diabetes such as online groups,

chats, other support groups, and diabetes education classes to enhance

involvement and support among patients with diabetes

• Inform patients about available resources for DM management such as diabetes education

classes.

• Create a support system in the VA and DoD healthcare systems such as online groups, chats, and

other support groups for patients with DM and other co-occurring conditions.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 97 of 160

Appendix E: Evidence Table

Recommendation

2010 

Grade1 Evidence2

Strength of 

Recommendation3

Recommendation 

Category4

1. We recommend shared decision-making to enhance

patient knowledge and satisfaction.

N/A [32]

Additional References:

[25,26,30,31,33]

Strong for Reviewed, New-added

2. We recommend that all patients with diabetes should be

offered ongoing individualized diabetes self-management

education via various modalities tailored to their

preferences, learning needs and abilities based on

available resources.

I

None

[34-38,40-44]

Additional Reference:

[39] 

Strong for Reviewed, New-replaced

3. We suggest offering one or more types of bidirectional

telehealth interventions (typically health communication

via computer, telephone or other electronic means)

involving licensed independent practitioners to patients

selected by their primary care provider as an adjunct to

usual patient care.

C

None

None

None

None

[45-49] Weak for Reviewed, New-replaced

4. We recommend setting an HbA1c target range based on

absolute risk reduction of significant microvascular

complications, life expectancy, patient preferences and

social determinants of health.

N/A [53-61]

Additional References: 

[50-52,62-66] 

Strong for Reviewed, New-added

1 The 2010 VA/DoD DM CPG used the USPSTF evidence grading system (http://www.uspreventiveservicestaskforce.org). Inclusion of more than one 2010 Grade indicates that 

more than one 2010 CPG recommendation is covered under the 2017 recommendation. The strength of recommendations were rated as follows: A- a strong 

recommendation that the clinicians provide the intervention to eligible patients; B- a recommendation that clinicians provide (the service) to eligible patients; C- no 

recommendation for or against the routine provision of the intervention is made; D- recommendation is made against routinely providing the intervention; I- the conclusion 

is that the evidence is insufficient to recommend for or against routinely providing the intervention. “None” indicates that the 2017 DM CPG recommendation replaced or 

amended a 2010 DM CPG recommendation for which there was no grade. “N/A” indicates that the 2017 DM CPG recommendation was a new recommendation, and 

therefore does not have an associated 2010 Grade. 2 The evidence column indicates studies that support each recommendation. For new recommendations, developed by the 2017 guideline Work Group, the literature cited 

corresponds directly to the 2016 evidence review. For recommendations that have been carried over from the 2010 VA/DoD DM CPG, slight modifications were made to the 

language in order to better reflect the current evidence and/or the change in grading system used for assigning the strength of each recommendation (USPSTF to GRADE). 

For these “modified” recommendations, the evidence column indicates “additional evidence,” which can refer to either 1) studies that support the recommendation and 

which were identified through the 2016 evidence review, or 2) relevant studies that support the recommendation, but which were not systematically identified through a 

literature review. 3 Refer to the Grading Recommendations section for more information on how the strength of the recommendation was determined using GRADE methodology. 4 Refer to the Recommendation Categorization section for more information on the description of the categorization process and the definition of each category.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 98 of 160

Recommendation

2010 

Grade1 Evidence2

Strength of 

Recommendation3

Recommendation 

Category4

5. We recommend developing an individualized glycemic

management plan, based on the provider’s appraisal of

the risk-benefit ratio and patient preferences.

C

None

Additional References:

[26,31,67] 

Strong for Reviewed, Amended

6. We recommend assessing patient characteristics such as

race, ethnicity, chronic kidney disease, and non-glycemic

factors (e.g., laboratory methodology and assay

variability) when interpreting HbA1c, fructosamine and

other glycemic biomarker results.

N/A [6]

Additional References:

[4,5,65,68-76] 

Strong for Reviewed, New-added

7. We recommend an individualized target range for HbA1c

taking into account individual preferences, presence or

absence of microvascular complications, and presence or

severity of comorbid conditions (See Table 2).

A [53,54,56-61,77,79-81]

Additional References:

[64,78,82-85] 

Strong for Reviewed, New-replaced

8. We suggest a target HbA1c range of 6.0-7.0% for

patients with a life expectancy greater than 10-15 years

and absent or mild microvascular complications, if it can

be safely achieved (See Table 2).

A [53,54,56-61,77,79-81]

Additional References:

[64,78,82-85] 

Weak for Reviewed, New-replaced

9. We recommend that in patients with type 2 diabetes, a

range of HbA1c 7.0-8.5% is appropriate for most

individuals with established microvascular or

macrovascular disease, comorbid conditions, or 5-10

years life expectancy, if it can be safely achieved (See

Table 2).

N/A [53,54,56-61,77,79-81]

Additional References:

[64,78,82-85] 

Strong for Reviewed, New-added

10. We suggest a target HbA1c range of 8.0-9.0% for

patients with type 2 diabetes with life expectancy <5

years, significant comorbid conditions, advanced

complications of diabetes, or difficulties in selfmanagement attributable to e.g., mental status,

disability or other factors such as food insecurity and

insufficient social support. (See Table 2).

A [53,54,56-61,77,79-81]

Additional References:

[64,78,82-85] 

Weak for Reviewed, New-replaced

11. We suggest that providers be aware that HbA1c

variability is a risk factor for microvascular and

macrovascular outcomes.

N/A [86]

Additional Reference:

[87]

Weak for Reviewed, New-added
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 99 of 160

Recommendation

2010 

Grade1 Evidence2

Strength of 

Recommendation3

Recommendation 

Category4

12. We recommend offering therapeutic lifestyle changes

counseling that includes nutrition, physical activity,

cessation of smoking and excessive use of alcohol, and

weight control to patients with diabetes (See VA/DoD

CPGs for obesity, substance use disorders, and 

tobacco use cessation).

None [88-93] Strong for Not Reviewed, Amended

13. We recommend a Mediterranean diet if aligned to

patient’s values and preferences. N/A [92,94,95] Strong for Reviewed, New-added

We recommend a nutrition intervention strategy 

reducing percent of energy from carbohydrate to 

14-45%per day and/or foods with lower glycemic index

in patients with type 2 diabetes who do not choose the

Mediterranean diet.

N/A [91-93,96,97,99] 

Additional Reference:

[98] 

Strong for Reviewed, New-added

15. We recommend against targeting blood glucose levels

<110 mg/dL for all hospitalized patients with type 2

diabetes receiving insulin.

A [100,101,103,104]

Additional References:

[102,105]

Strong against Reviewed, Amended

16. We recommend insulin be adjusted to maintain a blood

glucose level between 110 and 180 mg/dL for patients

with type 2 diabetes in critically ill patients or those with

acute myocardial infarction.

A [103,106,108-112,114]

Additional References:

[107,113] 

Strong for Reviewed, Amended

17. We recommend against the use of split mixed insulin

regimen for all hospitalized patients with type 2

diabetes.

N/A [115,116] Strong against Reviewed, New-added

18. We suggest a regimen including basal insulin and shortacting meal time or basal insulin and correction insulin

for non-critically ill hospitalized patients with type 2

diabetes.

N/A [111,114,117] Weak for Reviewed, New-added

19. We suggest providing medication education and

diabetes survival skills to patients before hospital

discharge.

I [120,121]

Additional References:

[118,119]

Weak for Reviewed, Amended

20. We recommend performing a comprehensive foot risk

assessment annually.

None [122-125] Strong for Not Reviewed, Amended

21. We recommend referring patients with limb-threatening

conditions to the appropriate level of care for evaluation

and treatment.

None [122,126-131] Strong for Not Reviewed, Amended

14.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 100 of 160

Recommendation

2010 

Grade1 Evidence2

Strength of 

Recommendation3

Recommendation 

Category4

22. We recommend a retinal examination (e.g., dilated

fundus examination by an eye care professional or

retinal imaging with interpretation by a qualified,

experienced reader) be used to detect retinopathy.

A [133]

Additional Reference:

[132] 

Strong for Not Reviewed, Amended

23. We suggest screening for retinopathy at least every

other year (biennial screening) for patients who have

had no retinopathy on all previous examinations. More

frequent retinal examinations in such patients should be

considered when risk factors associated with an

increased rate of progression of retinopathy are present.

Patients with existing retinopathy should be managed in

conjunction with an eye care professional and examined

at intervals deemed appropriate for the level of

retinopathy.

B

I Additional References:

[134-137] 

Weak for Not Reviewed, Amended

24. We recommend that all females with pre-existing

diabetes or personal history of diabetes and who are of

reproductive potential be provided contraceptive

options education and education on the benefit of

optimizing their glycemic control prior to attempting to

conceive.

None

Additional Reference:

[138] 

Strong for Not Reviewed, Amended

25. We recommend that all females with pre-existing None

Additional Reference:

[138] 

Strong for Not Reviewed, Amended

diabetes or personal history of diabetes who are

planning pregnancy be educated about the safest

options of diabetes management during the pregnancy

and referred to a maternal fetal medicine provider

(when available) before, or as early as possible, once

pregnancy is confirmed.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 101 of 160

Appendix F: 2010 Recommendation Categorization Table

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

D B 1 Children with diabetes should be referred for consultative care to a 

pediatric diabetic team that is knowledgeable and experienced in 

meeting the medical, psychosocial, and developmental needs of 

children with diabetes.

None Not reviewed, Deleted

D B 2 The pediatric diabetic team should include a pediatric 

endocrinologist, if available, and/or a pediatrician, certified diabetes 

educator, registered nurse, registered dietitian, and social worker, all 

with expertise and specialized training in the comprehensive care of 

children with diabetes.

None Not reviewed, Deleted

D C 1 All female patients with pre-existing diabetes and reproductive 

potential should be educated about contraceptive options, and 

strongly encouraged to plan and prepare for pregnancy, and to 

optimize their glycemic control prior to attempting to conceive.

None Not reviewed, Amended Recommendation 24

D C 2 Women with diabetes who are planning pregnancy should be 

educated about the different options of diabetes management 

during the pregnancy and referred to maternal fetal medicine 

provider before, or as early as possible, once pregnancy is confirmed.

None Not reviewed, Amended Recommendation 25 

D C 3 Women with gestational diabetes mellitus (GDM) should be 

screened for diabetes 6-12 weeks postpartum and should follow-up 

with subsequent screening for diabetes or prediabetes (See Module 

S: Screening)

None Not reviewed, Deleted

1 The first three columns indicate the location of each recommendation within the 2010 DM CPG.

2 The 2010 Recommendation Text column contains the wording of each recommendation from the 2010 DM CPG. 3 The 2010 VA/DoD DM CPG used the U.S. Preventive Services Task Force (USPSTF) evidence grading system. http://www.uspreventiveservicestaskforce.org The strength of 

recommendations were rated as follows: A- a strong recommendation that the clinicians provide the intervention to eligible patients; B- a recommendation that clinicians 

provide (the service) to eligible patients; C- no recommendation for or against the routine provision of the intervention is made; D- recommendation is made against 

routinely providing the intervention; I- the conclusion is that the evidence is insufficient to recommend for or against routinely providing the intervention. “None” indicates 

there was no grade assigned to the recommendation in the 2010 DM CPG. 4 The Category column indicates the way in which each 2010 DM CPG recommendation was updated. 

5 For recommendations that were carried forward to the 2010 DM CPG, this column indicates the new recommendation(s) to which they correspond.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 102 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

D E 1 Urgent or semi-urgent medical conditions, including hypo- or 

hyperglycemia, and deficient renal function must be treated before 

long-term disease management principles are applied.

None Not reviewed, Deleted

D E 2 The urgency of medical treatment, including the necessity for 

hospitalization, will depend upon the presence of ketoacidosis, 

dehydration, hyperosmolarity, infections, and other life threatening 

conditions.

None Not reviewed, Deleted

D E 3 Psychiatric illness and marked socioeconomic hardship (e.g., 

homelessness, absence of a support system or reliable 

transportation, and unemployment) pose significant barriers to 

diabetic management. If such circumstances are identified, 

involvement of behavioral health, social services, and case 

management professionals may enhance patient compliance with 

treatment and follow-up.

None Reviewed, Deleted

D E 4 The determination of stability is up to the judgment of the provider. None Not reviewed, Deleted

D F 1 In addition to a general medical examination, a complete evaluation 

of patients with DM will include: 

 Information regarding the onset and duration of DM

 History of hospitalization(s) for diabetic events

 Review of glycemic control

 Measurement of serum lipids

 Identification of foot complications

 Identification of eye complications

 Screening for hypertension

 Screening for kidney disease

 Identification of macrovascular disease

 Identification of neurovascular disease

 Assessment of psychosocial status (including family support)

 Appraisal of self-management skills

None Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 103 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

D F 2 On a follow-up visit, the evaluation should focus on updating new 

information and/or changes to the patient record (see Table D3 for a 

listing of the components of the evaluation).

None Not reviewed, Deleted

D H 1 Prescribe aspirin therapy (75 to 325 mg/day) for all adult patients 

with type 2 diabetes and evidence of cardiovascular disease.

A Not reviewed, Deleted

D H 2 Consider beginning aspirin therapy (75 to 325 mg/day) in patients 

age ≥ 40 with type 2 diabetes and one or more other cardiovascular 

risk factors.

B Not reviewed, Deleted

D H 3 Consider individual evaluation for aspirin therapy for patients age 30 

to 40 with type 2 DM, with other cardiovascular risk factors, or with 

type 1 DM for duration of disease longer than 2 years.

I Not reviewed, Deleted

D H 4 When considering the value of antiplatelet therapy, the risks of 

hemorrhagic stroke or gastrointestinal bleeding must be balanced 

against the benefits of prevention of adverse cardiovascular 

outcomes.

I Not reviewed, Deleted

D I 1 If the individualized HbA1c is not on target, refer to Module G –

Glycemic Control

None Not reviewed, Deleted

D I 2 Measure blood pressure on every diabetes visit. If systolic blood 

pressure (SBP) >140 mmHg or diastolic blood pressure (DBP) is >90 

mmHg, refer to the VA/DoD Clinical Practice Guideline for the 

Management of Hypertension. (Also see Annotation J)

None Not reviewed, Deleted

D I 3 Measure fasting lipids (TC, HDL-C, TG and calculated LDL-C) if not 

done within one year. If the patient has elevated cholesterol or 

lipids, refer to the VA/DoD Clinical Practice Guideline for the 

Management of Dyslipidemia (Lipids). (Also see Annotation K)

None Not reviewed, Deleted

D I 4 Screen for proteinuria and assess kidney function if not done within 

one year. If the patient develops micro- or macroalbuminuria or 

decline in estimated glomerular filtration rate (eGFR), refer to the 

VA/DoD Clinical Practice Guideline for the Management of Chronic 

Kidney Disease (CKD). (Also see Annotation L)

None Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 104 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

D I 5 Screen for retinopathy if not done within two years. If the patient 

has symptoms, or a previous exam showed a high-risk for visual loss 

or retinopathy, refer to Module E – Eye Care.

None Not reviewed, Deleted

D I 6 Complete a foot-risk assessment if not done within one year. If the 

patient has risk factors or an active lesion, refer to Module F – Foot 

Care.

None Not reviewed, Amended Recommendation 20

D I 7 If the patient needs additional nutritional or lifestyle education, refer 

to Module M – Self-Management and Education.

None Reviewed, Deleted

D I 8 If the patient is a candidate for an influenza vaccine, administer it in 

season. (See CDC recommendations)

None Not reviewed, Deleted

D I 9 Administer pneumococcal pneumonia vaccine, if indicated. (See CDC 

recommendations)

None Not reviewed, Deleted

D I 10 If the patient is using tobacco, refer to the VA/DoD Clinical Practice 

Guideline for the Management of Tobacco Use Cessation.

None Not reviewed, Deleted

D J 1 Patients with diabetes with hypertension (systolic BP ≥140 or 

diastolic BP ≥90 mmHg) should: a). Begin anti-hypertensive therapy 

with angiotensin converting enzyme inhibitor (ACEI) or a diuretic b). 

If ACEI induced side effects occur, consider switching to an 

angiotensin receptor blocker (ARB) c). Use other preferred agents 

(beta blockers, long acting calcium channel blockers) as necessary, 

depending on other co-morbid conditions or compelling indications 

to achieve a blood pressure <140/80 mm Hg.

A Not reviewed, Deleted

D J 2 Patients with diabetes with initial SBP <140 mmHg and DBP between 

80 and 89 mmHg (within the “pre-hypertensive” category identified 

by JNC 7) may benefit from lowering diastolic blood pressure to < 80 

mm Hg.

A Not reviewed, Deleted

D J 3 Individuals with diabetes whose blood pressure is <140/80 mmHg 

who have clinical cardiovascular disease may benefit from ACEI 

therapy even without a reduction in blood pressure.

A Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 105 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

D J 4 In patients with diabetes and kidney insufficiency (i.e., eGFR <60 

mL/min/1.73 m2

) and proteinuria (i.e., >1 g/24h) there are some data 

suggesting that further BP lowering (<125/75 mm Hg) may slow 

progression of renal disease. Lower BP should be achieved, if feasible 

and practical, depending on the tolerance of medications and side 

effects of BP lowering.

B Not reviewed, Deleted

D K 1 Patients with diabetes and patients with established coronary heart 

disease (CHD) should be screened for lipid abnormalities with fasting 

lipid profile (triglycerides and HDL-C or LDL-C).

None Not reviewed, Deleted

D K 2 Patients with Type 2 DM are at significant increased risk of CVD 

compared with non-diabetic patients of similar age and should, 

therefore, be treated more aggressively according to secondary 

prevention protocols.

A Not reviewed, Deleted

D K 5 LDL should be lowered to less than 100 mg/dL for patients with 

previous documented CHD or CVD equivalent (DM with other major 

risk factors) for secondary prevention.

A Not reviewed, Deleted

D K 6 LDL should be lowered to less than 130 mg/dL for patients with DM 

without other major risk factors for secondary prevention.

C Not reviewed, Deleted

D K 7 All patients with diabetes should be given lifestyle counseling. 

Lifestyle change is indicated in all patients with LDL-C > 100 mg/dL. 

Strategies include diet (dietary/nutritional management of fat and/or 

cholesterol intake or MNT consult), exercise, smoking cessation, 

cessation of excessive use of alcohol, and weight control.

None Not reviewed, Amended Recommendation 12

D K 8 Elevated TG level (>400 mg) may be due to poor glycemic control. 

The most common secondary causes of hypertriglyceridemia are 

alcohol, diabetes, and hypothyroidism. Addressing these underlying 

conditions can improve or normalize triglyceride levels and failing to 

address these conditions can render therapy ineffective. Once 

glycemic control is improved, the TG level should be reassessed and 

addressed.

None Not reviewed, Deleted

D K 9 Statin drug therapy should be initiated for patients with previous 

documented CHD or CVD equivalent (diabetes with other major risk 

factors) if baseline LDL-C is greater than or equal to 100 mg/dL.

A Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 106 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

D K 10 Statin drug therapy should be initiated for patients with documented 

DM with no major risk factors if baseline LDL-C is greater than or 

equal to 130 mg/dL.

C Not reviewed, Deleted

D K 11 Statin drug therapy should be considered for all patients with CHD or 

CVD equivalent (diabetes with other major risk factors) regardless of 

LDL-C baseline.

B Not reviewed, Deleted

D K 12 Therapeutic lifestyle changes (TLC) should be recommended for ALL 

patients with dyslipidemia, regardless of risk or baseline LDL-C level.

C Not reviewed, Deleted

D K 13 For secondary prevention of recurrent CVD events, nonpharmacologic therapy is always indicated, but it should not delay 

appropriate pharmacotherapy.

None Not reviewed, Deleted

D K 14 Emphasis on therapeutic lifestyle changes (TLC) is an important 

component of primary prevention and is effective in reducing CVD 

risk by lowering LDL-C and blood pressure.

B Not reviewed, Deleted

D K 15 Diet intervention should be the first step in lipid lowering therapy. B Not reviewed, Deleted

D K 16 Patients whose initial treatment is therapeutic lifestyle changes 

(TLC) should be given 3-6 months of dietary therapy prior to 

beginning medication and longer, if lipids are improving and nearing 

LDL thresholds.

B Not reviewed, Deleted

D K 17 Therapeutic lifestyle changes (TLC) is provided in a step-wise 

approach focused on initiating TLC components and followed by 

subsequent evaluation of the effect on LDL-C and moving to intensify 

MNT as indicated.

None Not reviewed, Deleted

D K 18 Statins are first line agents in primary and secondary prevention of 

CVD regardless of HDL-C or TG level.

A Not reviewed, Deleted

D K 19 Moderate doses of formulary statins (to achieve an LDL-C reduction 

of 25% or greater) should be initiated unless a patient is considered 

to be at greater than usual risk for adverse events from statins (e.g., 

myopathy).

A Not reviewed, Deleted

D K 20 For patients who cannot tolerate statins, niacin or resins should be 

considered for treatment.

A Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 107 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

D K 21 There is insufficient clinical outcome evidence to recommend 

ezetimibe monotherapy for reduction of CV risk.

I Not reviewed, Deleted

D K 22 Ezetimibe can be considered for lowering LDL-C in patients who are 

unable to tolerate other lipid-lowering drugs, or in combination with 

other drugs.

A Not reviewed, Deleted

D K 23 The dose of statin should be adjusted at 6 to 12 week intervals until 

individual LDL-C goals are achieved or statin doses have been 

maximized.

I Not reviewed, Deleted

D K 24 Niacin, fibrates, or fish oil (omega-3 fatty acids) supplements may be 

used in treatment of isolated hypertriglyceridemia.

B Not reviewed, Deleted

D K 25 For secondary prevention gemfibrozil or niacin may be used in 

patients with isolated low HDL-C and normal LDL-C. [A-Gemfibrozil; 

B-Niacin]

None Not reviewed, Deleted

D L 1 Patients with, diabetes, should be screened periodically for the 

presence of kidney disease.

C Not reviewed, Deleted

D L 2 Testing for kidney disease includes urinalysis and estimation of the 

glomerular filtration rate (eGFR).

B Not reviewed, Deleted

D L 3 Patients with diabetes who have a negative urine protein by dipstick 

should be tested for the presence of microalbuminuria.

B Not reviewed, Deleted

D L 4 Definitions of Chronic Kidney Disease includes any of the following: 

a). Persistent decreased eGFR <60 ml/min/1.73 m2 on two tests at 

least three months apart b). Proteinuria (> 1+) on dipstick or urine 

protein-to-creatine ratio > 0.2, confirmed on two tests at least three 

months apart c). Microalbuminuria defined as albumin-to-creatine 

ratio > 30, confirmed on two out of three urine tests in patients with 

diabetes mellitus (DM) d). Known structural kidney disease defined 

by imaging or pathologic examination (e.g., polycystic kidney disease 

[PCKD]) e). Estimated glomerular filtration rate (eGFR) is the 

preferred method to assess kidney function.

None Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 108 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

D L 5 The severity of CKD should be classified based on the level of the 

glomerular filtration rate (GFR) (see Table D-9). Kidney function 

should be assessed by formula-based estimation of GFR (eGFR), 

preferably using the 4-variable Modification of Diet in Renal Disease 

(MDRD) equation.

A Not reviewed, Deleted

D L 6 Microalbuminuria – in patients with diabetes – should be assessed 

using a laboratory method expressed as an albumin-to-creatinine 

ratio. If dipsticks designed to detect urinary microalbumin are used, 

positive tests should be followed by laboratory confirmation.

None Not reviewed, Deleted

D L 7 The diagnosis of microalbuminuria cannot be reliably made in the 

presence of an acute medical condition. As far as it is practicable, the 

best possible metabolic control of diabetes should be achieved 

before evaluating for microalbuminuria. Patients should not be 

screened during intercurrent illness or after heavy exercise.

None Not reviewed, Deleted

D L 8 It is important to consider other causes of increased albumin 

excretion, especially in the case of Type 1 diabetes present for < 5 

years. In addition to the previously mentioned conditions, other 

causes can include menstrual contamination, vaginal discharge, 

uncontrolled hypertension, and heart failure.

None Not reviewed, Deleted

D L 9 A 24-hour urine collection for protein and creatinine is not needed 

for quantitation of proteinuria, as it is more cumbersome for 

patients and prone to collection errors.

None Not reviewed, Deleted

D L 10 24-hour urine collection may be considered for: pregnant women,

extreme age and weight, malnutrition, skeletal muscle disease,

paraplegia or quadriplegia, patients with a vegetarian diet and

rapidly changing kidney function.

None Not reviewed, Deleted

D L 11 Serum creatinine level should be used to estimate the GFR to identify 

patients at risk and develop appropriate management plans.

None Not reviewed, Deleted

D L 12 Patients with diabetes with urine albumin/creatinine levels of ≥30 

μg/mg in the random specimen should repeat the test to ensure that 

the level was not transiently elevated (by heavy exercise, urinary 

tract infection, acute febrile illness, or heart failure).

None Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 109 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

D L 13 If a second test is ≥30 μg/mg, the patient has persistent 

microalbuminuria; if the second test is <30μg/mg, repeat the test a 

third time.

None Not reviewed, Deleted

D L 14 Persons with diabetes and macroalbuminuria (i.e., urine 

Alb/creatinine ratio ≥300 μg/mg or 24-hour urine protein ≥300 

mg/dL) should be assessed for level of kidney function as these levels 

of albuminuria indicate established to advanced diabetic kidney 

disease: a). Document the course of the albuminuria. It would be 

unusual to go from having normal urine to macroalbuminuria in less 

than one year in diabetic kidney disease b). Document if the blood 

pressure has been rising. As diabetic kidney disease progresses from 

micro- to macroalbuminuria, the blood pressure usually rises c). 

Document the presence of other diabetic complications, such as 

retinopathy. All patients with diabetes with macroalbuminuria 

should undergo an eye exam to screen for retinopathy (findings 

include microaneurysm, flame hemorrhage, and soft/hard exudates) 

(see Module E, Eye Care) because >90 percent of patients with 

macroalbuminuria from diabetes will also have at least mild 

retinopathy d). If the course has been atypical (i.e., rapidly 

progressive or no evidence of retinopathy), refer or consult with 

nephrology for further work-up e). Consider alternative explanations 

for reduced kidney function including pre-renal, renal, and post-renal 

causes f). Consider obtaining other tests and referral to specialists in 

nephrology or urology as indicated.

None Not reviewed, Deleted

D L 15 Nephrology consultation for help in diagnosis and treatment is 

indicated in: a). Patients with eGFR <30 ml/min/1.73 m2

) to facilitate 

education and planning for renal replacement therapy (dialysis or 

kidney transplant). b). Patients with kidney function that is 

deteriorating rapidly (e.g., eGFR decline of 50 percent eGFR from 

previous measure over 6 months or less). c). Patients with metabolic 

complications of CKD (e.g., anemia, secondary hyperparathyroidism). 

d). Patients with CKD of unclear etiology after the initial work up, or 

a known or suspected kidney condition requiring specialized care 

(e.g., a glomerulonephritis).

None Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 110 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

D L 16 Treatment of high blood pressure in DM-CKD should include 

identification of target blood pressure levels, nonpharmacologic 

therapy, and specific antihypertensive agents for the prevention of 

progression of kidney disease and development of cardiovascular 

disease.

None Not reviewed, Deleted

D L 17 (In patients with DM-CKD) Antihypertensive therapy should be 

adjusted to achieve blood pressure of < 130/80 mm Hg.

C Not reviewed, Deleted

D L 18 All patients with CKD with hypertension should be offered life-style 

advice, including maintenance of normal body weight (body mass 

index 18.5 to 24.9 kg/m2), reduction in dietary sodium intake (< 2 

g/day), regular aerobic physical exercise, smoking cessation, and 

limitation of alcohol intake.

B Not reviewed, Deleted

D L 19 There is insufficient evidence to recommend the routine 

implementation of a low protein diet (< 0.6g/kg/day) to slow the loss 

of GFR in patients with CKD.

D Not reviewed, Deleted

D L 20 (In patient with DM-CKD) A low protein diet may delay the onset of 

uremic symptoms in patients close to needing dialysis but this 

benefit must be weighed against the risk of protein malnutrition.

B Not reviewed, Deleted

D L 21 ACEIs or ARBs are the preferred agent for patients with kidney 

disease and hypertension. ACEIs may be preferred based on cost. 

ARBs may be substituted for patients with an ACEI induced cough.

A Not reviewed, Deleted

D L 22 Many patients (with DM-CKD) will require two or more medications 

to achieve their target blood pressure control. A diuretic should be 

used when a second blood pressure medication is needed, or if 

hyperkalemia occurs. Thiazide diuretics may be used if estimated 

GFR >30 ml/min/1.73 m2

, but loop diuretics are usually needed for 

patients with lower eGFR. Potassium-sparing diuretics should be 

used with caution in patients with CKD.

None Not reviewed, Deleted

D L 23 An increase of serum creatinine, as much as 30 percent above 

baseline, after ACEI or ARB initiation is common. ACEIs or ARBs 

should not be discontinued for this situation, since these 

medications are renoprotective.

None Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 111 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

D L 24 Patients with refractory hypertension, defined as inability to achieve 

goal blood pressure despite combination therapy with three drugs 

from complementary classes (including a diuretic), may benefit from 

an evaluation by a specialist in hypertension.

None Not reviewed, Deleted

D L 25 Patients with non-DM CKD with hypertension or diabetes with 

macroalbuminuria should be treated with an ACEI or ARB to slow the 

progression of kidney disease [A] and reduce proteinuria.

A Not reviewed, Deleted

D L 26 Patients with diabetes and microalbuminuria should be treated with 

an ACEI or ARB to slow the progression from microalbuminuria to 

macroalbuminuria, considered a surrogate for progression to CKD.

A Not reviewed, Deleted

D L 27 (In patient with DM-CKD) ACEIs and ARBs should be initiated at low 

doses and titrated to moderate to high doses as used in clinical trials.

A Not reviewed, Deleted

D L 28 There is insufficient evidence to recommend combination therapy 

with an ACEI and ARB to slow the progression of kidney disease 

except in a limited population of non-DM CKD.

I Not reviewed, Deleted

D L 29 (In patient with DM-CKD) Creatinine and potassium levels should be 

monitored one to two weeks after initiation or after a change in dose 

of ACEI or ARB therapy and periodically to maintain a normal range.

C Not reviewed, Deleted

D L 30 Treatment with an ACEI or ARB should not be initiated in patients 

with hyperkalemia (> 5.5).

D Not reviewed, Deleted

D L 31 (In patients with DM-CKD) People who develop cough on an ACEI 

should be switched to an ARB. Some people who develop 

angioedema on an ACEI may be switched to an ARB but require 

careful monitoring since some may also develop angioedema on an 

ARB.

C Not reviewed, Deleted

D L 32 In most patients (with DM-CKD), an ACEI or ARB should be continued 

unless: a). There is an acute GFR decline of > 30 percent within the 

first two weeks after initiation. b). Serum potassium is ≥ 6 mEq/L, 

despite appropriate treatment.

B Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 112 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

D L 33 Patients with CKD should be monitored for complication of CKD: 

disorders of potassium balance, calcium and phosphate metabolism, 

acid base abnormalities, hematologic abnormalities, volume 

overload, and exposure to nephrotoxic drugs.

None Not reviewed, Deleted

D L 34 Patients (with DM-CKD) may benefit from a dietary evaluation by a 

medical nutrition therapist and should be advised about a healthy 

diet and the preferred range of sodium, phosphate, and potassium in 

their diet.

C Not reviewed, Deleted

D L 35 Patients with CKD and an eGFR >30 ml/min/1.73 m2 with no 

associated co-morbidities should be followed up every 6 to 12 

months.

None Not reviewed, Deleted

D L 36 Patients with more advanced CKD should be referred to a 

nephrologist for consultation and/or continued follow-up.

None Not reviewed, Deleted

S A 1 Screening for pre-diabetes or diabetes should be considered for all 

adults age ≥45.

B Not reviewed, Deleted

S A 2 Screening for pre-diabetes or diabetes should be considered in 

younger adults who are overweight or obese (BMI ≥ 25 kg/m2) or are 

at high risk for DM based upon established risk factors (see Table S1) at 1-3 year intervals.

B Not reviewed, Deleted

S A 3 Screening for pre-diabetes or diabetes should occur at a frequency of 

1-3 years. More frequent screening can be performed depending

upon prior HbA1c or FPG results, and patient or clinician preferences.

I Not reviewed, Deleted

S A 4 Fasting plasma glucose (FPG) is the preferred diagnostic test for prediabetes and DM and is also a component of diagnostic testing.None Not reviewed, Deleted

S A 5 HbA1c can be used to screen for pre-diabetes or diabetes, when 

obtaining a blood sample in a fasting state is undesirable, but fasting 

plasma glucose test is required for the purpose of diagnosis. [B] The 

HbA1c test should be performed using clinical laboratory 

methodology standardized to the NSGP (not a Point of Care).

None Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 113 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

S A 6 A diagnosis of DM is made if any of the following: a). Fasting plasma 

glucose (FPG) is ≥126 mg/dL on at least two occasions, or b). A single 

HbA1c reading of ≥ 6.5%, confirmed with a FPG ≥126 mg/dL. These 

tests can be done on the same or different days; or c). HbA1c is ≥ 7% 

on two occasions using a clinical laboratory methodology 

standardized to the NSGP (not a Point of Care); or d). Symptoms of 

hyperglycemia and a casual (random) glucose ≥ 200 mg/dL on two 

occasions. However, casual (random) plasma glucose is not 

recommended as a routine screening test.

B Not reviewed, Deleted

S A 7 A diagnosis of pre-diabetes is made if any of the following: a). Fasting 

plasma glucose (FPG) readings with result < 126 mg/dL, but 

≥100mg/dL on two occasions b). HbA1c readings with result ≥5.7%, 

and confirmed with a FPG ≥100 mg/dL and <126 mg/dL. The FPG can 

be obtained at the same time as the HbA1c.

B Not reviewed, Deleted

S A 8 Although the oral glucose tolerance test can also be used for the 

diagnosis of diabetes, it’s is not recommended in the primary care 

setting.

C Not reviewed, Deleted

S A 9 Random plasma glucose is not recommended as a routine screening 

test.

C Not reviewed, Deleted

S B 1 Patients with pre-diabetes should be counseled about the risks of 

progression to diabetes and the rationale for implementing 

preventive strategies. [A] Individuals with risk factors for diabetes 

who are not diagnosed with pre-diabetes should also be counseled 

and educated about how to reduce risks.

A Not reviewed, Deleted

S B 2 Lifestyle modifications to prevent diabetes, including regular aerobic 

exercise and a calorie-restricted diet to promote and maintain 

weight loss, should be instituted in patients with pre-diabetes.

A Not reviewed, Deleted

S B 3 An individualized goal to achieve and sustain weight loss of ≥ 5 

percent of body weight should be set for patients with risk factor for 

diabetes and a BMI ≥ 25.

A Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 114 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

S B 4 When lifestyle modifications have been ineffective at preventing a 

sustained rise in glucose, the patient may be offered pharmacologic 

therapy with a metformin or an alpha-glucosidase inhibitor (e.g., 

acarbose) to delay progression from pre-diabetes to a diagnosis of 

diabetes.

A Not reviewed, Deleted

G B 1 HbA1c should be measured in patients with diabetes at least 

annually, and more frequently (up to 4 times per year) if clinically 

indicated, to assess glycemic control over time.

None Not reviewed, Deleted

G B 2 Self Monitoring of Blood Glucose (SMBG) may be used to monitor 

glycemic control and adjust treatment.

B Not reviewed, Deleted

G B 3 Patients, for whom SMBG is appropriate, should receive instruction 

on the proper procedure, the importance of documenting results, 

and basic interpretation and application of results to maximize 

glycemic control.

None Not reviewed, Deleted

G B 4 SMBG results should be discussed with the patient to promote 

understanding, adjust treatment regimens, and facilitate treatment 

adherence.

B Not reviewed, Deleted

G B 5 Remote electronic transmission of SMBG data should be considered 

as a tool to assess glycemic patterns.

C Reviewed, New-replaced Recommendation 3

G B 6 The frequency of SMBG in patients using insulin should be 

individualized based on the frequency of insulin injections, 

hypoglycemic reactions, level of glycemic control, and 

patient/provider use of the data to adjust therapy.

C Not reviewed, Deleted

G B 7 A combination of pre-and postprandial tests may be performed, up 

to 4 times per day.

C Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 115 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

G B 8 The schedule of SMBG in patients on oral agents (not taking insulin) 

should be individualized, and continuation justified based upon 

individual clinical outcomes. Consider more frequent SMBG for the 

following indications: a). Initiation of therapy and/or active 

adjustment of oral agents b). Acute or ongoing illness c). Detection 

and prevention of hypoglycemia when symptoms are suggestive of 

such, or if there is documented hypoglycemia unawareness d). 

Detection of hyperglycemia when fasting and/or post-prandial blood 

glucose (PPG) levels are not consistent with HbA1c.

None Not reviewed, Deleted

G C 1 Treat diabetes more aggressively early in its course. B Not reviewed, Deleted

G C 2 The target range for glycemic control should be individualized, based 

on the provider’s appraisal of the risk-benefit ratio and discussion of 

the target with the individual patient.

C Reviewed, Amended Recommendation 5 

G C 3 Providers should recognize the limitations of the HbA1c 

measurement methodology reconciling the differences between 

HbA1c readings and self-monitoring results on a case-by-case basis.

None Reviewed, Deleted

G C 4a Setting the initial target range should consider the following: (see 

Table G-1) The patient with either none or very mild microvascular 

complications of diabetes, who is free of major concurrent illnesses, 

and who has a life expectancy of at least 10-15 years, should have an 

HbA1c target of <7 percent, if it can be achieved without risk.

A Reviewed, New-replaced

Reviewed, New-replaced

Recommendation 7

Recommendation 8

G C 4b Setting the initial target range should consider the following: (see 

Table G-1) Any patient with diabetes should have a HbA1c target of 

<9 percent to reduce symptoms of hyperglycemia.

C Not reviewed, Deleted

G C 4c Setting the initial target range should consider the following: (see 

Table G-1) The patient with longer duration diabetes (more than10 

years) or with comorbid conditions, and who require combination 

medication regimen including insulin, should have an HbA1c target 

of < 8 percent.

A Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 116 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

G C 4d Setting the initial target range should consider the following: (see 

Table G-1) The patient with advanced microvascular complications 

and/or major comorbid illness, and or a life expectancy of less than 5 

years is unlikely to benefit from aggressive glucose lowering 

management and should have a HbA1c target of 8-9 percent.

A Reviewed, New-replaced Recommendation 10

G C 4e Setting the initial target range should consider the following: (see 

Table G-1) Risk of hypoglycemia should be considered in 

recommending a target goal.

B Not reviewed, Deleted

G D 1 Risks of a proposed therapy should be balanced against the potential 

benefits, based upon the patient’s medical, social, and psychological 

status.

None Not reviewed, Deleted

G E 1 The patient and provider should agree on a specific target range of 

glycemic control after discussing the risks and benefits of therapy.

None Not reviewed, Deleted

G E 2 The patient should be assessed for knowledge, performance skills, 

and barriers (e.g., psychosocial, personal, or financial), and if 

necessary referred to a primary care case manager or 

endocrine/diabetes clinic to address barriers for achieving treatment 

goals.

None Reviewed, New-replaced Recommendation 3
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 117 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

G F 1 The indications to consider a consultation or referral to specialty 

include patients who: a). Have type 1 DM; especially patients with 

history of hospitalizations for metabolic complications and/or 

patients who are receiving intensive insulin therapy b). Have newonset insulin-requiring DM c). Have marked insulin resistance d). 

Have contraindications or intolerances to medications typically used 

in managing diabetes e). Have recurrent episodes of incapacitating 

hypo- and/or hyperglycemia f). Have poor recognition of 

hypoglycemia and who have a history of severe hypoglycemic 

reactions (including coma, seizures, or frequent need for emergency 

resuscitation) g). Have visual and/or renal impairment h). Have 

psychosocial problems (including alcohol or substance abuse) that 

complicate management i). Have HbA1c > 9.0 percent and are 

considered for aggressive management on an expedited basis j). Are 

not achieving glycemic control despite comprehensive treatment 

with complex regimen of combination pharmacotherapy including 

insulin k). Require evaluation or management beyond the level of 

expertise and resource level of the primary team

None Not reviewed, Deleted

G G 1 The patient with type 1 diabetes mellitus (DM) must receive insulin 

replacement therapy.

None Not reviewed, Deleted

G G 2 Patients with type 2 diabetes, or diabetes of undetermined cause 

who exhibit significant or rapid weight loss and/or persistent nonfasting ketonuria, have at least severe relative insulin deficiency and 

will require insulin therapy on an indefinite basis.

None Not reviewed, Deleted

G H 1 All patients with type 1 DM should be managed by a provider 

experienced in managing type 1 DM in a multidisciplinary approach 

or by a clinic team with multidisciplinary resources (e.g., 

diabetologist, diabetes nurse, educator/manager, and registered 

dietitian) for institution and adjustment of insulin therapy.

None Not reviewed, Deleted

G H 2 When expeditious referral is not possible, the primary care provider 

should institute “survival” insulin therapy comprised of total daily 

insulin (TDI) 0.5 units/kg/day; half as basal insulin and half as meal 

time insulin.

None Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 118 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

G I 1 Patients with diabetes should be regularly assessed for knowledge, 

performance skills, and barriers to self-management.

None Reviewed, New-replaced Recommendation 3

G I 2 Patients with recurrent or severe hypoglycemia should be evaluated 

for precipitating factors that may be easily corrected (e.g., missed 

meals, incorrect administration of insulin [dosage or timing], and 

exercise).

None Not reviewed, Deleted

G I 3 If psychosocial, personal, or financial barriers are identified, 

additional resources should be consulted, as applicable (e.g., mental 

health, medical social work, or financial counselors).

None Reviewed, New-replaced Recommendation 3 

G J 1 Individual treatment goals must be established with the patient 

based on the extent of the disease, comorbid conditions, and patient 

preferences.

None Not reviewed, Deleted

G J 2 Institution of dietary modification and exercise alone is usually the 

appropriate initial management in patients with new onset type 2 

diabetes, depending upon severity of symptoms, psychosocial 

evaluation, patient motivation, and overall health status. Encourage 

diet and exercise and lifestyle modifications.

None Not reviewed, Deleted

G J 3 Use various approaches (e.g., individual or group, counseling, 

coaching, motivational interviewing) to promote healthful behaviors, 

such as healthful diet, adequate physical activity, and smoking 

cessation.

None Not reviewed, Deleted

G J 4 If treatment goals are not achieved with diet and exercise alone, 

drug therapy should be initiated while encouraging lifestyle 

modifications.

None Not reviewed, Amended

G J-1 1 (Monotherapy/ Initial therapy) When selecting an agent, 

consideration must be given to efficacy, contraindications, drug 

interactions, and side effects. Educate patient about treatment 

options and arrive at a shared treatment plan with consideration for 

patient preferences.

I Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 119 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

G J-1 2 (Monotherapy/ Initial therapy) Insulin should be considered in any 

patient with extreme hyperglycemia or significant symptoms; even if 

transition to therapy with oral agents is intended as hyperglycemia 

improves. (See section on insulin for further details.)

B Not reviewed, Deleted

G J-1 3 (Monotherapy/ Initial therapy) Metformin (preferred) or 

sulfonylureas (SU) should be given as first line agents unless there 

are contraindications.

A Not reviewed, Deleted

G J-1 4 Alternative monotherapy agents such as thiazolidinediones (TZDs), 

alpha-glucosidase inhibitors (AGIs), meglitinides, dipeptidyl 

peptidase-4 (DPP-4) inhibitors, and glucagon-like peptide-1(GLP-1) 

agonists should be reserved for patients who have contraindications 

to or are unable to tolerate metformin or SU.

B Not reviewed, Deleted

G J-1 5 Patients and their families should be instructed to recognize signs 

and symptoms of hypoglycemia and its management.

I Reviewed, New-replaced Recommendation 2

G J-2 1 (Combination therapy/ Add-on) Metformin + sulfonylurea is the 

preferred oral combination for patients who no longer have 

adequate glycemic control on monotherapy with either drug.

A Not reviewed, Deleted

G J-2 2 (Combination therapy/ Add-on) Other combinations (TZDs, AGIs, 

meglitinides, DPP-4 inhibitors, and GLP-1 agonists) can be considered 

for patients unable to use metformin or a sulfonylurea due to 

contraindications, adverse events, or risk for adverse events (see 

Appendices G-2 and G-3).

B Not reviewed, Deleted

G J-2 3 (Combination therapy/ Add-on) Addition of bedtime NPH or daily 

long-acting insulin analog to metformin or sulfonylurea should be 

considered, particularly if the desired decrease in HbA1c is not likely 

to be achieved by use of combination oral therapy.

A Not reviewed, Deleted

G J-2 4 Patients and their families should be instructed to recognize signs 

and symptoms of hypoglycemia and its management.

I Reviewed, New-replaced Recommendation 2

G J-3 1 Use of insulin therapy should be individualized, and managed by a 

healthcare team experienced in managing complex insulin therapy 

for patients with type 1 DM

I Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 120 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

G J-3 2 Use intermediate- or long-acting insulin to provide basal insulin 

coverage.

B Not reviewed, Deleted

G J-3 3 Insulin glargine or detemir may be considered in the NPH insulintreated patient with frequent or severe nocturnal hypoglycemia.B Not reviewed, Deleted

G J-3 4 Use regular insulin or short-acting insulin analogues for patients who 

require mealtime coverage.

None Not reviewed, Deleted

G J-3 5 Alternatives to regular insulin (aspart, lispro, or glulisine) should be 

considered in the following settings: a). Demonstrated requirement 

for pre-meal insulin coverage due to postprandial hyperglycemia 

AND concurrent frequent hypoglycemia b). Patients using insulin 

pump

B Not reviewed, Deleted

G J-4 1 Continuous subcutaneous insulin infusion (CSII) therapy should only 

be initiated and managed by an endocrinologist/diabetes team with 

expertise in insulin pump therapy

None Not reviewed, Deleted

G J-4 2 Continuous subcutaneous insulin infusion (CSII) therapy should only 

be considered in patients who have either documented type 1 

diabetes [history of DKA, low c-peptide or evidence of pancreatic 

autoimmunity] or be insulin deficient with a need for intensive 

insulin therapy to maintain glycemic control and are not able to 

maintain it using multiple daily injections (MDI) therapy.

None Not reviewed, Deleted

G J-4 2a Continuous subcutaneous insulin infusion (CSII) therapy should only 

be considered in patients who have either documented type 1 

diabetes [history of DKA, low c-peptide or evidence of pancreatic 

autoimmunity] or be insulin deficient with a need for intensive 

insulin therapy to maintain glycemic control and are not able to 

maintain it using multiple daily injections (MDI) therapy. This may 

include patients with poor glycemic control (including wide glucose 

excursions with hyperglycemia and serious hypoglycemia and those 

not meeting HbA1c goal) despite an optimized regimen using MDI in 

conjunction with lifestyle modification.

A Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 121 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

G J-4 2b Continuous subcutaneous insulin infusion (CSII) therapy should only 

be considered in patients who have either documented type 1 

diabetes [history of DKA, low c-peptide or evidence of pancreatic 

autoimmunity] or be insulin deficient with a need for intensive 

insulin therapy to maintain glycemic control and are not able to 

maintain it using multiple daily injections (MDI) therapy. This may 

include patients with marked dawn phenomenon (fasting AM 

hyperglycemia) not controlled using NPH at bedtime, glargine or 

detemir.

B Not reviewed, Deleted

G J-4 2c Continuous subcutaneous insulin infusion (CSII) therapy should only 

be considered in patients who have either documented type 1 

diabetes [history of DKA, low c-peptide or evidence of pancreatic 

autoimmunity] or be insulin deficient with a need for intensive 

insulin therapy to maintain glycemic control and are not able to 

maintain it using multiple daily injections (MDI) therapy. This may 

include patients with recurrent nocturnal hypoglycemia despite 

optimized regimen using glargine or detemir.

B Not reviewed, Deleted

G J-4 2d Continuous subcutaneous insulin infusion (CSII) therapy should only 

be considered in patients who have either documented type 1 

diabetes [history of DKA, low c-peptide or evidence of pancreatic 

autoimmunity] or be insulin deficient with a need for intensive 

insulin therapy to maintain glycemic control and are not able to 

maintain it using multiple daily injections (MDI) therapy. This may 

include patients with circumstances of employment or physical 

activity, for example shift work, in which multiple daily injections 

(MDI) regimens have been unable to maintain glycemic control.

I Not reviewed, Deleted

G J-4 3 Patients using continuous subcutaneous insulin infusion (CSII) should 

have: a). Demonstrated willingness and ability to play an active role 

in diabetes self-management to include frequent self-monitoring of 

blood glucose (SMBG), and to have frequent contact with their 

healthcare team. b). Completed a comprehensive diabetes education 

program.

None Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 122 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

G J-4 4 The use of continuous subcutaneous insulin infusion (CSII) over 

multiple daily injections (MDI) regimens is not recommended in most 

patients with type 2 diabetes.

D Not reviewed, Deleted

G J-5 1 In patients with known DM, it is reasonable to document the DM 

diagnosis in the medical record. Because of the potential harm from 

omission of insulin in patients with type 1 DM, it is suggested that 

the type of DM also be documented.

I Not reviewed, Deleted

G J-5 2 In order to identify potentially harmful hyperglycemia and 

hypoglycemia, blood glucose monitoring may be ordered in 

hospitalized patients with diagnosed DM and/or hyperglycemia (BG > 

180 mg/dL) on admission. There is no evidence to support a given 

frequency of monitoring. Therefore, the frequency of monitoring 

should be based upon clinical judgment taking into account the 

management of diabetes, the reason for admission, and the stability 

of the patient.

I Reviewed, Deleted

G J-5 3 Due to safety concerns related to potential adverse events with oral 

anti-hyperglycemic medications, it is prudent to thoughtfully review 

these agents in the majority of hospitalized patients. It may be 

reasonable to continue oral agents in patients who are medically 

stable and have good glycemic control on oral agents at home.

I Not reviewed, Deleted

G J-5 4 For patients with DM and/or hyperglycemia who are not medically 

stable or who are poorly controlled with oral anti-hyperglycemic 

medications at home, initiating insulin therapy should be considered. 

It is appropriate to continue pre-hospitalization insulin regimens, but 

reasonable to reduce the dose in order to minimize the risk of 

hypoglycemia. In the ICU, continuous intravenous insulin infusion is 

recommended. Scheduled subcutaneous insulin is appropriate in the 

non-ICU setting and may include a long-acting basal insulin as well as 

a nutritional insulin for those eating discrete meals or receiving 

enteral nutrition. A supplementary correction (sliding) scale is also 

recommended but correction scale insulin regimens as sole therapy 

are discouraged.

B Reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 123 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

G J-5 5 Insulin should be adjusted to maintain a BG < 180 mg/dL with the 

goal of achieving a mean glucose around 140 mg/dL. Evidence is 

lacking to support a lower limit of target blood glucose but based on 

a recent trial suggesting that blood glucose < 110 mg/dL may be 

harmful, we do not recommend blood glucose levels < 110 mg/dL. 

A Reviewed, Amended Recommendation 15 

Recommendation 16

G J-5 6 Insulin therapy should be guided by local protocols and preferably 

“dynamic” protocols that account for varied and changing insulin 

requirements. A nurse-driven protocol for the treatment of 

hypoglycemia is highly recommended to ensure prompt and 

effective correction of hypoglycemia.

I Not reviewed, Amended

G J-5 7 To minimize the risk of hypoglycemia and severe hyperglycemia after 

discharge it is reasonable to provide hospitalized patients who have 

DM and knowledge deficits, or patients with newly discovered 

hyperglycemia, basic education in “survival skills”.

I Reviewed, Amended Recommendation 19 

G J-5 8 Patients who experienced hyperglycemia during hospitalization but 

who are not known to have DM should be re-evaluated for DM after 

recovery and discharge.

B Not reviewed, Deleted

G K 1 The patient with recurrent or severe hypoglycemia should be 

evaluated for precipitating factors that may be easily correctable 

(e.g., missed meals, exercise, incorrect administration of insulin—

dosage or timing).

None Not reviewed, Deleted

G L 1 If the patient does not achieve his/her target range, the provider 

should identify barriers to patient adherence to the treatment 

regimen (e.g., miscommunication, lack of education or 

understanding, financial/social/psychological barriers, and cultural 

beliefs).

None Not reviewed, Deleted

G L 2 If barriers are identified, referral to a case manager or 

behavioral/financial counselor may be considered as appropriate.

None Not reviewed, Deleted

G M 1 Treatment goals should be periodically reassessed based upon 

patient specific factors, including changes in the patient’s health 

status, adverse drug reactions, adherence to therapy, and 

preferences.

None Reviewed, Amended Recommendation 5 
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 124 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

G N 1 Patients should be scheduled for appropriate follow-up to evaluate 

response, tolerability to therapy, goal re-assessment, and 

management of acute and chronic problems: a). The frequency of 

follow-up visits for the patient with diabetes who is meeting 

treatment goals and who has no unstable chronic complications 

should be individualized b). When there is a sudden change in health 

status or when changes are made to the treatment regimen, followup within one month or sooner may be appropriate.

None Not reviewed, Deleted

G N 2 Treatment goals should be periodically reassessed based upon 

patient-specific factors, including changes in the patient’s health 

status, adverse drug reactions, adherence to therapy, and 

preferences.

None Reviewed, Amended Recommendation 5

E A 1 Patients with an acute change in vision or a change in ocular function 

should be urgently referred to an eye care provider.

None Not reviewed, Deleted

E B 1 Patients with either early diabetes onset (age <30 years) or type 1 

diabetes at a later age should have an initial examination when the 

time from diabetes diagnosis is >3 years.

B Not reviewed, Deleted

E C 1 Patients who are newly diagnosed with type 2 DM and have not had 

an eye exam within the past 12 months should have a retinal 

examination performed within 6 months

B Not reviewed, Deleted

E C 2 A retinal examination (e.g. dilated fundus examination by an eye care 

professional or retinal imaging with interpretation by a qualified, 

experienced reader) should be used to detect retinopathy.

A Not reviewed, Amended Recommendation 22

E D 1 Patients who have had no retinopathy on all previous examinations 

should be screened for retinopathy at least every other year 

(biennial screening). More frequent retinal examinations in such 

patients should be considered when risk factors associated with an 

increased rate of progression of retinopathy are present.

B Not reviewed, Amended Recommendation 23

E D 2 Patients with existing retinopathy should be managed in conjunction 

with an eye care professional and examined at intervals deemed 

appropriate for the level of retinopathy.

I Not reviewed, Amended Recommendation 23
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 125 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

F A 1 The patient’s feet should be visually inspected for: a). Breaks in the 

skin b). Erythema c). Trauma d). Pallor on elevation e). Dependent 

rubor f). Changes in the size or shape of the foot g). Nail deformities 

h). Extensive callus i). Tinea pedis j). Pitting edema

I Not reviewed, Deleted

F B 1 A foot risk assessment must be performed and documented at least 

once a year. A complete foot risk assessment includes: a). Evaluation 

of the skin for breakdown b). Assessment of protective sensation 

using the Semmes-Weinstein 5.07 monofilament c). Evaluation for LE 

arterial disease d). Evaluation for foot deformity e). Prior history of 

ulcers or amputations. In addition, the patient’s footwear should be 

evaluated.

None Not reviewed, Deleted

F C 1 Evaluation should be performed for limb-threatening conditions, 

such as systemic infection, acute ischemia/rest pain, foot ulceration, 

puncture wound, ingrown toenail, and hemorrhagic callus with or 

without cellulitis.

None Not reviewed, Deleted

F D 1 Patients with limb-threatening conditions should be referred to the 

appropriate level of care for evaluation and treatment.

None Not reviewed, Amended Recommendation 21

F D 2 If the patient’s symptoms limit his/her lifestyle, a vascular specialist 

should determine the appropriateness of surgical intervention on a 

patient-specific basis. Justification of vascular procedures should be 

based on the outcomes of the vascular interventions.

None Not reviewed, Deleted

F E 1 Patients without limb-threatening conditions should be evaluated for 

their level of risk for LE foot ulcers and amputations.

None Not reviewed, Deleted

F E 2 The existence of one of the following characteristics is sufficient to 

define the patient as high-risk for foot problem a). Lack of sensation 

to Semmes-Weinstein 5.07 monofilament at one or more 

noncallused plantar sites b). Evidence of LE arterial disease (absence 

of both dorsalis pedis and tibialis posterior pulses, dependent rubor 

with pallor on elevation, history of rest pain or claudication, and 

prior history of LE bypass surgery) c). Foot deformities (specifically 

hammer toes, claw toe, Charcot's arthropathy, bunions, and 

metatarsal head deformities) d). History of foot ulcer or nontraumatic LEA at any level.

None Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 126 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

F E 3 The patient at high-risk should be referred to a foot care specialist 

for a more comprehensive evaluation and intensive treatment plan 

including patient education concerning foot care practices, hygiene, 

and footwear.

None Not reviewed, Deleted

F F 1 Minor lesions or wounds that could possibly be treated by the 

primary care provider are blisters, erosions, and/or minor cuts that 

do not extend beyond subcutaneous tissue. Pulses are present, there 

are no signs of acute infection, and there is no severe lower limb 

pain and no sign of a worsening lesion.

None Not reviewed, Deleted

F F 2 Patients with an ingrown toenail should be referred to a foot 

specialist for evaluation and treatment (see Annotation C, Ingrown 

Toenail).

None Not reviewed, Deleted

F G 1 High-risk patients with a minor foot wound or lesion should be 

promptly referred to a foot care specialist (i.e., podiatrist, vascular 

surgeon, orthopedic surgeon, and other healthcare providers with 

demonstrated training, competence, and licensure in foot care) for 

evaluation and treatment.

None Not reviewed, Deleted

F G 2 Footwear prescriptions should be based upon individual

characteristics of foot structure and function.

None Not reviewed, Deleted

F H 1 All patients and their families should receive self-management 

education for preventive foot care and selection of footwear. 

Instruction should include recommendations for daily foot inspection 

and preventive foot care, skin care, and use of emollients, nail care, 

and treatment for callus.

None Not reviewed, Deleted

F I 1 Visual inspection and peripheral sensation testing in high-risk patient 

should be performed at each routine primary care visit for all 

patients (see Annotation A).

None Not reviewed, Deleted

F J 1 Patients with diabetes with minor wounds or foot lesions should 

have a wound assessment.

None Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 127 of 160 

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

F J 2 The wound assessment includes: a). A review of anatomic, physical, 

and lesion characteristics including determination of circumference, 

depth, and involvement of deep structures b). Assessment for signs 

of infection including necrosis, sinus tracts, exudate, odor, presence 

of fibrin, and healthy granulation tissue c). Assessment of 

surrounding areas for signs of edema, cellulitis, or abscess.

None Not reviewed, Deleted

F K 1 Patients with diabetes with uncomplicated minor lesions should 

receive local wound care. Primary care providers should attempt to 

offload weight-bearing on the affected extremity.

None Not reviewed, Deleted

F K 2 Patients with diabetes with uncomplicated minor lesions must be 

followed at least monthly.

None Not reviewed, Deleted

F L 1 Patients with diabetes treated for an uncomplicated wound should 

be assessed within four weeks from the initial wound assessment for 

appropriate reduction in lesion size and depth and appearance of 

healthy granulating tissue with no evidence of infection.

None Not reviewed, Deleted

F M 1 Minor foot problems (e.g., onychomycosis, painful corn, dry skin, 

athlete’s foot, minor calluses, uncomplicated nail trimming and 

improper foot hygiene) may be treated by a primary care provider in 

the office, or by the patient or family members at home (see 

Annotation F).

None Not reviewed, Deleted

F N 1 Assure that patient and family members have received appropriate 

education regarding preventive foot care.

None Not reviewed, Deleted

F N 2 Treat minor foot problems, as appropriate. None Not reviewed, Deleted

M B 1 Ensure that patients newly diagnosed with DM are provided with 

core competency education. The core competencies include: a). 

Acute complications (hyperglycemia and hypoglycemia) b). 

Medication education c). Self-monitoring of blood glucose and how 

to use the results d). Basic diet principles e). Sick day management f). 

When to seek further assistance (See Appendix M-1: Core 

Competencies [Survival Skills] for Patients with Diabetes).

None Not reviewed, Deleted

M C 1 Patients newly diagnosed with diabetes should receive 

comprehensive DSME and education for MNT.

None Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 128 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

M C 2 DSME, including MNT education, should be an interactive, 

collaborative, ongoing process involving patients with diabetes and 

educators and include the following four-step process: a). 

Assessment of the patient’s educational needs b). Identification of 

the patient’s specific self-management goals c). Education and 

behavioral interventions aimed at meeting the patient’s goals d). 

Evaluation of the patient’s progress towards the goals

None Not reviewed, Deleted

M C 3 The education component should be tailored to the patient’s needs 

and provided by healthcare professionals who are most 

knowledgeable in the topic. Regardless of setting, availability of a 

multidisciplinary team approach is highly desirable and could 

include, but is not limited to, a dietitian, certified diabetes educator, 

registered nurse, pharmacist, psychologist, exercise physiologist, 

physical therapist, social worker, endocrinologist, behaviorist, 

ophthalmologist, optometrist, physician, podiatrist, other healthcare 

professionals and paraprofessionals, or other specialized physicians 

based on the individual patient’s needs.

None Not reviewed, Deleted

M C 4 The use of approaches such as group visits and telehealth should be 

considered in providing education.

None Reviewed, New-replaced Recommendation 3

M D 1 Assessment of the following factors should be completed to 

determine the extent of the patient’s educational and skills deficit 

and his/her ability for self-management: knowledge of the diabetes 

disease process, treatment goals, management skills, cultural 

influences, health beliefs/behavior, attitudes, socioeconomic factors 

and barriers.

None Not reviewed, Deleted

M D 2 Documentation of the patient’s learning needs, abilities including 

physical and cognitive limitations, or language barriers, preferences, 

cultural and religious practices, emotional barriers, health literacy 

and numeracy, desire and motivation to learn and/or change, and 

the financial implications of care choices.

None Not reviewed, Deleted

M D 3 Assessment and documentation of the patient’s understanding of 

education.

None Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 129 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

M E 1 Conditions that may warrant risk-focused intervention include: a). 

Markedly or persistently elevated HbA1c (For appropriate HbA1c 

target based on risk stratification, see Module G: Table G-1) b). 

Progression to ESRD (e.g., stage 3-5 CKD) c). Lower extremity 

complications d). Pregnancy, or planned pregnancy, or woman of 

child bearing age e). Impaired vision f). Severe psychosocial or 

economic barriers g). Cognitive impairment or frailty h). Intensive 

insulin therapy i). Recurrent hypoglycemia or hypoglycemia 

unawareness j). Recent hospitalization for diabetic ketoacidosis 

(DKA), hyperosmolar hyperglycemic state disease complexity

None Not reviewed, Deleted

M F 1 Patients at high-risk may have needs beyond educational deficits and 

should be referred for focused attention by other services. Possible 

referrals could include, but are not limited to: case manager, 

registered nurse, registered dietitian, pharmacist, psychologist, 

exercise physiologist, physical therapist, social worker, 

endocrinologist, ophthalmologist, optometrist, physician, podiatrist, 

behaviorist, other healthcare professionals, or paraprofessionals.

None Not reviewed, Deleted

M F 2 Refer to case manager for providing ongoing, detailed coordination 

of care for high-risk patients.

None Not reviewed, Deleted

M G 1 When knowledge deficits continue to exist or a large number of 

lifestyle changes are necessary, frequent follow-up may be indicated.

None Not reviewed, Deleted

M G 2 Recently learned diabetes skills or information should be reevaluated no longer than 3 months after initial instruction. One 

possible method involves follow-up at earlier time points, e.g., 1 

month.

None Not reviewed, Deleted

M G 3 When appropriate, single behavioral goals should be identified and 

prioritized to increase the likelihood of the patient adopting lifestyle 

changes necessary to achieve treatment goals.

None Not reviewed, Deleted

M J 1 Diabetes education is effective for improving clinical outcomes and 

quality of life, at least in the short-term.

None Not reviewed, Deleted

M J 2 DSME has evolved from primarily didactic presentations to more 

theoretically based empowerment models.

None Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 130 of 160

2010 

Recommendation 

Location1

2010 Recommendation Text2

2010 Grade3

Category4

2017 

Recommendation (if 

applicable)5

ModuleSectionNumber

M J 3 There is no one “best” education program or approach; however, 

programs incorporating behavioral and psychosocial strategies 

demonstrate improved outcomes. Additional studies show that 

culturally and age appropriate programs improve outcomes and that 

group education is effective.

None Reviewed, New-replaced Recommendation 2

M J 4 Ongoing support is critical to sustain progress made by participants 

during the DSME program.

None Not reviewed, Deleted

M J 5 Behavioral goal-setting is an effective strategy to support selfmanagement behaviors.None Not reviewed, Deleted
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 131 of 160

Appendix G: Participant List

Department of Defense

Maj Jeffrey A. Colburn, MD, FACP (Champion) 

Staff Endocrinologist

Diabetes Champion

San Antonio Military Medical Center

Fort Sam Houston, TX

Elizabeth (Liz) Rees Atayde, RN, MSN, FNP, CCM, CPHM

Nursing, Medical Management

Nurse Case Manager/ CPG Consultant 

US Army Medical Command 

Fort Sam Houston, TX

Amy M. Lugo, PharmD, BCPS, BC-ADM, FAPhA

Clinical Pharmacy Specialist

Director, Managed Care Residency 

Defense Health Agency Pharmacy Operations Division

Formulary Management Branch

San Antonio, TX

Susan McReynolds, RD, CDE 

Dietitian

Madigan Army Hospital

Joint Base Lewis-McChord

Tacoma, WA 

Maj Tracy L. Snyder, MS, RD 

Registered Dietitian

Director of Operations

348th (Health Professions) Recruiting Squadron

Clearfield, UT

Evan N. Steil, MD, MBA, MHA 

Administrative Physician

US Army Medical Command 

Clinical Performance Assurance Directorate 

Fort Sam Houston, TX

Elaine P. Stuffel, RN, BSN, MHA

Ambulatory Nursing

Chronic Disease Clinical Practice Guideline Coordinator, 

Office of Evidence Based Practice

US Army Medical Command 

Quality Management Division

JBSA Fort Sam Houston, TX

COL Gwendolyn H. Thompson, PharmD 

Pharmacotherapy Specialist

Director, Medication Safety

HQ, US Army Medical Command (Patient Safety)

Clinical Performance Assurance Directorate

Fort Sam Houston, TX

LCDR Mark P. Tschanz, DO, MACM, FACP

Associate Program Director, Internal Medicine 

Residency

Naval Medical Center San Diego

San Diego, CA

Nina A. Watson, MSN, RN, CDE 

Diabetes Educator, Outreach Team

Diabetes Center of Excellence 

Wilford Hall Ambulatory Surgical Center 

Lackland AFB, TX
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 132 of 160

Department of Veterans Affairs

Leonard Pogach, MD, MBA, FACP (Champion)

National Director, Medicine 

Office of Patient Care Services (Office of Specialty Care)

Veterans Affairs Central Office 

Washington, DC

David C. Aron, MD, MS

Director of Clinical Program Research and Education

Senior Scholar, VA Quality Scholars Program

Louis Stokes Cleveland VA Medical Center

Cleveland, OH

Paul R. Conlin, MD

Chief, Medical Service

VA Boston Healthcare System

Vice Chair for VA Boston Affairs, Department of 

Medicine, Brigham and Women’s Hospital

Boston, MA

Mercedes Falciglia, MD, FACP

Medical Director, Diabetes Now

University of Cincinnati

Acting Chief Endocrinology, Cincinnati VA Medical Center

Cincinnati, OH

Chester B. Good, MD, MPH, FACP

Chair, Medical Advisory Panel for Pharmacy Benefits 

Management

Department of Veterans Affairs

VA Pittsburgh Healthcare System

Pittsburgh, PA

Mary M. Julius, RD, LD, CDE

Clinical Coordinator, Diabetes Self-Management 

Education and Support 

Research Dietitian 

Louis Stokes Cleveland Department of Veterans Affairs

Cleveland, OH

Deborah Khachikian, PharmD

National PBM Clinical Pharmacy Program Manager

Pharmacy Benefits Management Service 

Hines, IL

Rose Mary Pries, DrPH

National Program Manager

Office of Veterans Health Education & Information

VHA National Center for Health Promotion & Disease 

Prevention

Department of Veterans Affairs

Durham, NC

Sharon A. Watts, DNP, FNP-BC, CDE

ONS Clinical Nurse Advisor 

Chair, Office of Nursing Services and Diabetes Field 

Advisory Committee

Veterans Hospital of Cleveland

Cleveland, OH
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 133 of 160

Appendix H: Literature Review Search Terms and Strategy

A. Topic-specific Search Terms

The search strategies employed combinations of free-text keywords as well as controlled vocabulary 

terms including (but not limited to) the following concepts. Strategies for each bibliographic database 

follow this table.

Table H-1. Embase

Set # Concept Strategy

Type 2 Diabetes Mellitus

1 

T2DM – core set

'non insulin dependent diabetes mellitus'/exp OR 'adult onset diabetes' OR 'adult 

onset diabetes mellitus' OR 'diabetes mellitus type 2' OR 'diabetes mellitus type ii' 

OR 'diabetes mellitus, maturity onset' OR 'diabetes mellitus, non insulin 

dependent' OR 'diabetes mellitus, non-insulin-dependent' OR 'diabetes mellitus, 

type 2' OR 'diabetes mellitus, type ii' OR 'diabetes type 2' OR 'diabetes type ii' OR 

'diabetes, adult onset' OR 'dm 2' OR 'insulin independent diabetes' OR 'insulin 

independent diabetes mellitus' OR 'ketosis resistant diabetes mellitus' OR 

'maturity onset diabetes' OR 'maturity onset diabetes mellitus' OR 'maturity onset 

diabetes of the young' OR 'niddm' OR 'non insulin dependent diabetes' OR 'non 

insulin dependent diabetes mellitus' OR 'noninsulin dependent diabetes' OR 

'noninsulin dependent diabetes mellitus' OR 'type 2 diabetes' OR 'type 2 diabetes 

mellitus' OR 'type ii diabetes' OR ‘T2DM’

2 #1 AND [humans]/lim AND [English]/lim

3 

#2 AND ('book'/it OR 'chapter'/it OR 'conference abstract'/it OR 'conference 

paper'/it OR 'conference review'/it OR 'editorial'/it OR 'erratum'/it OR 'letter'/it 

OR 'note'/it OR 'short survey'/it)

4 #2 NOT #3

5 #4 AND ([young adult]/lim OR [adult]/lim OR [middle aged]/lim OR [aged]/lim OR 

[very elderly]/lim) AND [2009-2016]/py

Intensive Glycemic Control

6 

Intensive glycemic 

control

((‘ACCORD’ NEAR/2 (study OR trial)) OR ‘Action to control cardiovascular risk in 

diabetes trial’)

7 ((‘ADVANCE’ NEAR/2 (study OR trial)) OR ‘Action in diabetes and vascular 

disease’)

8 ((‘VADT’ NEAR/2 (study OR trial)) OR ‘Veterans affairs diabetes trial’)

9 #6 OR #7 OR #8

10 (intensive OR tight) NEAR/2 ('glycemic control' OR 'glycaemic control')

11 ‘intensive glucose lowering’

12 #9 OR #10 OR #11

13 #5 AND #12

14 Embase study type 

filters

('clinical article'/de OR 'clinical trial'/de OR 'clinical trial (topic)'/de OR 

'comparative study'/de OR 'controlled clinical trial'/de OR 'controlled study'/de 

OR 'dosage schedule comparison'/de OR 'drug dose comparison'/de OR 'evidence 

based medicine'/de OR 'major clinical study'/de OR 'meta analysis'/de OR 'meta 

analysis (topic)'/de OR 'multicenter study'/de OR 'phase 2 clinical trial (topic)'/de 

OR 'phase 3 clinical trial (topic)'/de OR 'practice guideline'/de OR 'prospective 

study'/de OR 'randomized controlled trial'/de OR 'randomized controlled trial 

(topic)'/de OR 'systematic review'/de OR 'systematic review (topic)'/de)
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 134 of 160

Set # Concept Strategy

15 ECRI broad trial filter

'randomized controlled trial'/exp OR 'randomization'/de OR 'double blind 

procedure'/de OR 'single blind procedure'/de OR 'placebo'/de OR 'latin square 

design'/de OR 'crossover procedure'/de OR 'triple blind procedure'/de OR 

'controlled study'/exp OR 'clinical trial'/exp OR 'comparative study'/exp OR 

'cohort analysis'/de OR 'follow up'/de OR 'intermethod comparison'/de OR 

'parallel design'/de OR 'control group'/de OR 'prospective study'/de OR 

'retrospective study'/de OR 'case control study'/exp OR 'major clinical study'/de 

OR 'evaluation study'/exp OR random*:de OR random*:ti OR placebo* OR (singl* 

OR doubl* OR tripl* OR trebl* AND (dummy OR blind OR sham)) OR 'latin square' 

OR isrctn* OR actrn* OR (nct* NOT nct)

16 ECRI broad metaanalysis filter

‘meta-analysis/de OR 'research synthesis' OR pooled OR ‘meta-analysis’ OR 

‘meta-analytic’

17 ECRI systematic review 

filter

'systematic review'/de OR 'systematic review' OR search*:ab

18 Combine sets #13 AND (#14 OR #15 OR #16 OR #17)

Shared Decision-making

19

Decision making

'patient decision making'/de OR 'patient decision making' OR 'clinical decision 

making'/de OR 'clinical decision making' OR 'clinical decision-making' OR 'decision 

making'/de OR 'choice behavior' OR 'choice behaviour' OR 'decision making' OR 

'decision making task' OR 'decision process'

20 shared

21 'patient-centered' OR patient* NEAR/2 (preference* OR priorit*) OR patient* 

NEAR/5 (shared OR sharing OR centered OR trust)

22 ‘diabetic patient’/de

23 Goal NEAR/2 set*

24

Combine sets

#5 AND #19 AND (#20 OR #21)

25 #21 AND #22

26 #23 AND (#5 OR #22)

27 #24 OR #25 OR #26

28

Limit to diabetes as a 

major concept

#27 AND (‘non insulin dependent diabetes mellitus’/exp/mj OR diabet*:ti)

29 SDM AND (‘non insulin dependent diabetes mellitus’/exp/mj OR diabet*:ti)

30 #28 OR #29
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 135 of 160

Set # Concept Strategy

Telehealth

31

Telehealth

‘telehealth’/exp

32

telehealth* OR telecare* OR telediagnos* OR telemonitor* OR telemanag* OR 

teleconsult* OR teledermatol* OR telehomecare* OR telematics OR telepathol* 

OR telepharm* OR telenurs* OR telepsychiatr* OR telestroke OR telesupport

33

(tele OR remote) NEAR/2 (health OR care* OR diagnos* OR monitor* OR manag* 

OR consult* OR home* OR nurs* OR dermatol* OR pathol* OR pharmac* OR 

nurs* OR psychiatr* OR stroke OR support)

34

'connected care' OR 'ehealth' OR 'e-health' OR 'e-connected' OR 'etherapy' OR 'etherapy' OR 'mhealth' OR 'm-health' OR 'wired for health' OR 'virtual care' OR 

'computer mediated therapy' OR 'econsult' OR 'e-icu' OR 'patient portal' OR video 

NEAR/2 (visit* OR consult*)

35

'health care'/exp/mj AND ('mass communication'/de OR 'e-mail'/de OR 

'interactive voice response system'/de OR 'internet'/de OR 'mass medium'/de OR 

'mobile phone'/de OR 'social media'/de OR 'telephone'/de OR 'text messaging'/de 

OR 'videoconferencing'/de OR 'wireless communication'/de OR 'online 

system'/de)

36

'health care'/exp/mj AND (internet*:ti OR computer*:ti OR web*:ti OR 

interactive*:ti OR telecommunication*:ti OR telephone*:ti OR phone*:ti OR 

sms:ti OR video*:ti OR email:ti OR 'e-mail':ti OR wireless:ti OR bluetooth:ti)

37 #31 OR #32 OR #33 OR #34 OR #35 OR #36

38

Combine sets

#5 AND #37

39 #38 AND #15 [ECRI RCT filter]

40 #38 AND #14 [Embase study filter]

41 #39 OR #40

Medical Nutrition Therapy 

42

MNT 

#5 AND ‘nutrition’/exp

43 #42 AND (‘disease management’/lnk OR ‘therapy’/lnk OR ‘treatment 

outcome’/exp)

44 #5 AND ‘diabetic diet

45 #5 AND ‘diet therapy’/exp/mj

46 #5 AND (‘MNT’ OR ‘medical nutrition therapy’ OR ‘medical nutrition therapies’)

47 #5 AND (‘MeDiet’ OR (Mediterranean* NEAR/2 diet*) OR ‘mediterranean 

diet’/de)

48

#5 AND (diet NEAR/2 ('low carbohydrate' OR 'low energy' OR 'low fat' OR 'low 

glycemic index' OR 'low glycaemic index' OR 'carbohydrate counting' OR 'carb 

counting' OR ada OR vegan OR nordic)):ti

49 #43 OR #44 OR #45 OR #46 OR #47 OR #48

50

Limit by study types

#49 AND (‘randomized’:ti OR ‘randomised’:ti OR ‘randomized controlled trial’/de)

51 #49 AND (‘systematic review’/de OR “systematic review” OR ‘meta analysis’/de 

OR (meta* NEAR/2 (analysis OR analyses OR analytic)))

52 #50 OR #51

53

Limit to treatment of 

diabetes using 

subheading

#52 AND 'diabetes mellitus'/exp/dm_th
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 136 of 160

Set # Concept Strategy

54 Limit to nutrition as a 

major concept

#52 AND ‘nutrition’/exp/mj

55 Combine sets #53 OR #54

56

Eliminate phrase Diet NEAR/2 ‘inadequately controlled’

57 #55 NOT #56

Self-management Education

58

Patient education

'patient education'/de OR 'education, patient' OR 'patient education' OR 'patient 

education as topic' OR 'patient medication knowledge'

59 'education'/de OR 'diabetes education'/de OR 'health education'/de OR 'health 

promotion'/de

60

'teaching'/exp OR 'computer-assisted instruction' OR 'patient simulation' OR 

'programmed instruction' OR 'programmed instruction as topic' OR 'programmed 

teaching' OR 'remedial school' OR 'remedial teaching' OR 'school, remedial' OR 

'student teaching' OR 'teaching' OR 'teaching aid' OR 'teaching material' OR 

'teaching materials' OR 'teaching method' OR 'teaching program' OR 'teaching 

programme' OR 'teaching, programmed' OR 'teaching, remedial'

61

(patient* OR adult* OR client* OR participant* OR individual* OR diabetes) 

NEAR/3 (train* OR educat* OR teach* OR instruct* OR inform* OR counsel* OR 

empower*)

62 #58 OR #59 OR #60 OR #61

63 Combine sets #5 AND #62

64

Self-management

'self care'/exp OR 'self care' OR 'self management' OR 'self treatment'

65

'disease management'/de OR 'disease management' OR 'diseases management' 

OR 'disorder management' OR 'disorders management' OR 'illness management' 

OR 'management of disease' OR 'management of disorder' OR 'medical 

management' AND (self*:ti OR patient*:ti OR individual*:ti OR group*:ti)

66 self* NEAR/4 (care OR efficac* OR manag* OR monitor*)

67 #64 OR #65 OR #66

68

Blood glucose 

monitoring (BGM)

'blood glucose monitoring'/de OR 'blood glucose control' OR 'blood glucose 

monitoring' OR 'blood glucose self-monitoring' OR 'monitoring, blood glucose'

69 Blood NEAR/2 (glucose OR sugar) NEAR/3 monitor*

70 #68 OR #69

71

Combine sets – 

education & self 

management

#63 AND #67

72 Combine sets – 

education & BGM

#63 AND #70

73 Combine sets #71 OR #72

74

Limit by study types

#73 AND ('randomized controlled trial'/de OR 'randomized controlled trial 

(topic)'/de)

75

#73 AND ('randomised':ti OR 'randomized:ti' OR 'systematic review'/de OR 

'systematic review' OR 'critical review' OR 'meta-analysis'/de OR meta NEAR/2 

analy*)

76 #74 OR #75
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 137 of 160

Set # Concept Strategy

Metrics

77 Blood glucose

'glucose blood level'/de OR 'blood glucose' OR 'blood glucose level' OR 'blood 

serum glucose' OR 'blood sugar' OR 'blood sugar level' OR 'glucosaemia' OR 

'glucose blood level' OR 'glucose, blood' OR 'glucose, plasma' OR 'glucosemia' OR 

'glycaemia' OR 'glycemia' OR 'normoglycaemia' OR 'normoglycemia' OR 'plasma 

glucose' OR 'postprandial glycaemia' OR 'postprandial glycemia' OR 'serum 

glucose' OR 'serum sugar' OR 'blood glucose monitoring'/de

78

Metrics

'continuous glucose monitoring' OR 'cgms' OR 'cbgms' OR 'cgm' OR 'cgbm'

79 'glycosylated hemoglobin'/exp OR 'hba1c' OR 'a1c' OR 'hgba1c'

80 'eag' OR 'estimated average glucose'

81 'fructosamine blood level'/exp OR 'fructosamine'/de OR fructosamine OR fbs

82 '1,5 anhydrosorbitol'/exp OR '1,5 anhydrosorbitol' OR '1,5-anhydroglucitol' OR 

'1,5-anydro-d-glucitol' OR '1,5-ag'

83 #78 OR #79 OR #80 OR #81 OR #82

84 Combine sets #77 AND #83 AND [humans]/lim AND [English]/lim and [2009-2016]/py

85

Limiting concepts

‘measure’:ti OR ‘measures’:ti OR ‘indices’:ti OR indicator*:ti

86 (glycemic OR glycaemic) NEAR/2 indicator*

87 correlation*:ti OR relationship*:ti

88 #85 OR #86 OR #87

89 Combine sets #84 AND #88

Metformin as 1st-line Therapy

90 Drug therapy ‘drug therapy’ limiter

91 Metformin

'metformin'/de OR '1, 1 dimethylbiguanide' OR 'apophage' OR 'aron' OR 

'benofomin' OR 'dabex' OR 'denkaform' OR 'deson' OR 'dextin' OR 'diabetase' OR 

'diabetase s' OR 'diabetformin' OR 'diabetmin' OR 'diabetmin retard' OR 

'diabetosan' OR 'diabex' OR 'diafat' OR 'diaformin' OR 'diaformina' OR 'diaformina 

lp' OR 'diametin' OR 'diamin' OR 'diformin' OR 'diformin retard' OR 'dimefor' OR 

'dimethylbiguanide' OR 'dimethyldiguanide' OR 'dmgg' OR 'dybis' OR 'eraphage' 

OR 'espa-formin' OR 'euform retard' OR 'fluamine' OR 'flumamine' OR 'fornidd' 

OR 'fortamet' OR 'glafornil' OR 'glibudon' OR 'glifage' OR 'gliguanid' OR 

'glucaminol' OR 'glucofage' OR 'glucofago' OR 'glucoform' OR 'glucoformin' OR 

'glucohexal' OR 'glucoless' OR 'glucomet' OR 'glucomin' OR 'glucomine' OR 

'gluconil' OR 'glucophage' OR 'glucophage forte' OR 'glucophage retard' OR 

'glucophage sr' OR 'glucophage xr' OR 'glucophage xr extended release' OR 

'glucophage-mite' OR 'glucotika' OR 'gludepatic' OR 'glufor' OR 'gluformin' OR 

'glumeformin' OR 'glumet' OR 'glumetza' OR 'glupa' OR 'glustress' OR 'glyciphage' 

OR 'glycomet' OR 'glycon' OR 'glycoran' OR 'glyformin' OR 'glymet' OR 

'haurymellin' OR 'hipoglucin' OR 'i-max' OR 'islotin' OR 'juformin' OR 'la 6023' OR 

'la6023' OR 'maformin' OR 'meglucon' OR 'meguan' OR 'melbin' OR 'melformin' 

OR 'mellittin' OR 'mescorit' OR 'metaformin' OR 'metfogamma' OR 'metforal' OR 

'metformin' OR 'metformin hydrochloride' OR 'metformine' OR 'methformin' OR 

'metiguanide' OR 'metomin' OR 'metphormin' OR 'miformin' OR 'n` 

dimethylguanylguanide' OR 'n` dimethylguanylguanidine' OR 'n`, n` 

dimethyldiguanide' OR 'n, n dimethyl biguanidine' OR 'n, n dimethylbiguanide' OR 

'n, n dimethylbiguanide retard' OR 'n, n dimethylbiguanidine' OR 'n, n 

dimethyldiguanide' OR 'n, n dimethylguanylguanidine' OR 'neoform' OR 'nndg' OR 

'reglus-500' OR 'riomet' OR 'siamformet' OR 'siofor' OR 'thiabet' OR 'vimetrol' OR 

'walaphage'

92 Combine sets #90 OR #91
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 138 of 160

Set # Concept Strategy

93 Core diabetes set #5

94 Combine sets #92 AND #93

95 1st-line (first OR ‘1st’) NEAR/2 line

96 Combine sets #94 AND #95

97

Limit by study type

#96 AND ('systematic review'/de OR 'systematic review' OR 'critical review' OR 

'meta-analysis'/de OR meta NEAR/2 analy*)

98

#96 AND ('randomised':ti OR 'randomized:ti' OR ‘randomized controlled trial’/de 

OR 'clinical trial'/de OR 'comparative study'/de OR 'controlled clinical trial'/de OR 

'controlled study'/de OR 'intermethod comparison'/de OR 'multicenter study'/de 

OR 'practice guideline'/de OR 'prospective study'/de)

99 #97 OR #98

Non-ICU Inpatient Insulin Management 

100

Inpatient

'hospital patient'/de OR 'hospital patient' OR 'hospitalised patient' OR 

'hospitalised patients' OR 'hospitalized patient' OR 'hospitalized patients' OR 'inhospital patient' OR 'in-hospital patients' OR 'inpatient' OR 'inpatients' OR 

'patient, hospital' OR 'hospital care'/de OR inpatient*:ti OR hospital*:ti OR ward:ti

101 'after hospital stay' OR ('post-discharge' OR postdischarge) NEAR/2 ('glycemic 

control' OR 'glycaemic control')

102 #100 OR #101

103 ICU 'intensive care'/de OR 'care, intensive' OR 'critical care' OR 'intensive care' OR 

'intensive therapy' OR 'therapy, intensive' OR 'icu' OR 'ccu'

104 Inpatient NOT ICU #102 NOT #103

105 Non-ICU patients with 

diabetes

#4 AND #104

106

Insulin dosing

'insulin derivative'/exp OR 'carbamoylinsulin' OR 'carbamylinsulin' OR 'carbonyl 

bis methionyl insulin' OR 'diacetoacetyl insulin' OR 'diacetylinsulin' OR 

'diaminosuberoyl insulin' OR 'insulin analog' OR 'insulin analogue' OR 'insulin 

derivative' OR 'insulins' OR 'methylthiocarbamoylinsulin' OR 

'methylthiocarbamylinsulin' OR 'mononitroinsulin' OR 'polyalanylinsulin series' OR 

'suberoyl insulin' OR 'succinyl insulin' OR 'triacetylinsulin' OR 'tricarbamylinsulin'

107

'insulin treatment'/exp OR 'insulin'/de OR 'actrapid insulin' OR 'actrapid mc' OR 

'cross linked insulin' OR 'destripeptide insulin' OR 'fish insulin' OR 'humilin' OR 

'iletin ii' OR 'immunoinsulin' OR 'in 105' OR 'in105' OR 'initard' OR 'insulin' OR 

'insulin (animal source)' OR 'insulin actrapid' OR 'insulin hnc' OR 'insulin novo 

actrapid' OR 'insulin snc' OR 'insulina pronta lilly' OR 'insuline' OR 'insulinum' OR 

'iodinated insulin' OR 'iszilin' OR 'maxirapid' OR 'monotard human' OR 'monotard 

insulin' OR 'neusulin' OR 'novolin' OR 'oralin' OR 'oro insulin' OR 'teleost insulin'

108

(fixed NEAR/2 (dose OR dosing)) OR (basal NEAR/5 correction) OR ‘drug dose 

titration’/de OR (sliding NEAR/2 scale) OR (basal NEAR/2 bolus) OR (insulin 

NEAR/2 protocol)

109 (#106 OR #107) AND #108

110 Combine sets #105 AND #109

111

Limit to RCTs, SRs, and 

Mas 

#110 AND (‘randomized’:ti OR ‘randomised’:ti OR ‘randomized controlled 

trial’/de)

112 #110 AND (‘systematic review’/de OR “systematic review” OR ‘meta analysis’/de 

OR (meta* NEAR/2 (analysis OR analyses OR analytic)))

113 #111 OR #112
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 139 of 160

Set # Concept Strategy

Non-ICU Inpatient Blood Glycemic Target

114

Glycemic target

iatrogenic NEAR/5 (hypoglycemi* OR hypoglycaemi* OR hyperglycemi* OR 

hyperglycaemi* OR dysglycemi* OR dysglycaemi*)

115 (blood NEAR/2 (sugar OR glucose)) AND (moderate NEAR/3 control)

116 (glycemic OR glycaemic) NEAR/2 target*

117 '200 mg/dl' OR '11.1 mmol/l' OR '11.1 mmol/liter'

118 ‘hospital patient’/de AND ‘glycemic control’/de

119 #114 OR #115 OR #116 OR #117 OR #118

120 Combine sets #105 AND #119

121 #120 AND (‘randomized’:ti OR ‘randomised’:ti OR ‘randomized controlled 

trial’/de)

122 #120 AND (‘systematic review’/de OR “systematic review” OR ‘meta analysis’/de 

OR (meta* NEAR/2 (analysis OR analyses OR analytic)))

123 Combine sets #121 OR #122

124 Limit #123 NOT (gestational OR 'pre-gestational' OR pregnan*):ti

Transitions of Care - Education

125

Care management and 

education

(patient OR individual* OR group OR participant* OR diabetes) AND (educat* OR 

train* OR teach* OR instruct* OR inform* OR counsel* OR empower*)

126 ((care OR transition*) NEAR/2 (management OR plan*))

127 ‘transitional care’/de OR transition*:ti

128 ‘dsme’

129 #125 OR #126 OR #127 OR #128

130 Combine sets #105 AND #129

131

Limit to RCTs, SRs, and 

MA’s 

#130 AND (‘randomized’:ti OR ‘randomised’:ti OR ‘randomized controlled 

trial’/de)

132 #130 AND (‘systematic review’/de OR “systematic review” OR ‘meta analysis’/de 

OR (meta* NEAR/2 (analysis OR analyses OR analytic)))

133 Controlled trials #130 AND ((controlled OR control*) NEAR/2 group) OR controls:ab OR ‘controlled 

trial’/de)

134 Combine sets #131 OR #132 OR #133

Effect of Glucose Variability on Microvascular and Macrovascular Outcomes

135

Complications

'diabetic angiopathy'/de OR 'diabetic nephropathy'/de OR 'diabetic 

neuropathy'/de OR 'diabetic retinopathy'/de OR 'diabetic cardiomyopathy'/de OR 

‘diabetic foot’/de

136 microvascular OR 'micro-vascular' OR 'macrovascular' OR 'macro-vascular' AND 

(disease* OR outcome* OR complication*)

137 ‘Kidney disease’/exp/mj

138 ‘peripheral vascular disease’/exp/mj

139 ‘heart disease’/exp/mj

140 #136 OR #137 OR #138 OR #139

141 #140 AND (‘non insulin dependent diabetes mellitus’/exp OR diabet*:ti)

142 #135 OR #141
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 140 of 160

Set # Concept Strategy

143

Glycemic variability

‘glycemic control’/de OR ((glycemic OR glycaemic) NEAR/2 control)

144 (glycemic OR glycaemic OR 'blood glucose') NEAR/2 (variab* OR oscillat* OR 

excursion* OR fluctuation*)

145 #143 OR #144

146 Combine sets #142 AND #145

147 Combine sets #5 AND #146

EMBASE.com Syntax:

* = truncation character (wildcard)

NEAR/n = search terms within a specified number (n) of words from each other in any order

NEXT/n = search terms within a specified number (n) of words from each other in the order 

specified

/ = search as a subject heading

exp = “explodes” controlled vocabulary term (e.g., expands search to all more specific related 

terms in the vocabulary’s hierarchy)

mj = denotes a term that has been searched as a major subject heading

:de = search in the descriptors field (controlled terms and keywords)

:lnk = floating subheading

:it,pt. = source item or publication type 

:ti. = limit to title 

:ti,ab. = limit to title and abstract fields
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 141 of 160

Topic-specific Search Terms

Concept Controlled Vocabulary Keywords/PubMed Concepts 

Diabetes EMBASE

‘diabetes’/exp

‘non insulin dependent diabetes 

mellitus’/exp

adult onset diabet*

‘diabetes mellitus type 2’

‘diabetes mellitus type II’

‘diabetes mellitus maturity onset’

‘insulin independent diabetes’

‘ketosis resistant diabetes’

‘non insulin dependent’

“noninsulin dependent”

“non-insulin-dependent”

DM2

NIDDM

T2D

T2DM

“type 2”

“type-2”

“type II”

“type-II”

Specific trials EMBASE ACCORD

“Action to Control Cardiovascular 

Risk in Diabetes”

ADVANCE

“Action in diabetes and vascular 

disease”

DIMORA (not sure of relevance – 

older patients)

VADT

“Veterans Affairs Diabetes Trial”

Care Management EMBASE

‘hospital discharge’/de

‘transitional care’/de

‘after hospital stay’

Bundled

DSME

Post NEAR/1 hospital*

‘post-discharge’

‘postdischarge’

Transition*:ti

‘transition care’

Discharge planning and transition 

management

EMBASE

‘Hospital discharge’/de

‘Primary medical care’/de

‘Health care planning’/de

‘Health care access’/de

(discharge OR transition) NEAR/3

(plan* OR service* OR 

management)

‘diabetes care’ NEAR/3 ‘hospital 

discharge’
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 142 of 160

Concept Controlled Vocabulary Keywords/PubMed Concepts 

Glucose measurement EMBASE

‘blood glucose monitoring’/de

‘continuous glucose monitoring’/de

‘glucose blood level’/de

‘glycemic control’/de

eAG

‘estimated average glucose’

‘hospital monitored average 

glucose’

HMAG 

Glycemic control

Glycaemic control

Glycemic excursions

Glycaemic excursions

Glycemic variability

Glycaemic variability

Glucose variability

1,5-anhydro-D-glucitol (1,5-AG)

A1c

CGMS

‘continuous glucose monitoring’

GA

Gap measurement

Glycation gap

Glycosylation gap

Glycated albumin

adjGA

FBS

HbA1c

HgA1c

‘mean amplitude’

MAGE 

‘M value’
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 143 of 160

Concept Controlled Vocabulary Keywords/PubMed Concepts 

Glycemic variability and threshold EMBASE

‘glycemic control’/de

A1c variability

Glycemic control

Glycaemic control

Glycemic excursions

Glycaemic excursions

Glycemic variability

Glycaemic variability

Glucose variability

Glycosylated hemoglobin

HbA1c variability

‘lower threshold’

‘180 mg/dl’

‘200 mg/dl’

’10.0 mmol/L’

’10.0 mmol/liter’

’11.1 mmol/L’

’11.1 mmol/liter’

Glycemic target

Glycaemic target

Inpatient EMBASE

‘hospital patient’/de

‘hospitalization’/de

hospital

hospitalised

hospitalized

inpatient

‘in-patient’

Inpatient insulin management EMBASE

‘hospital patient’/de

‘insulin’/de

Reviewed related citations from 

PMID 24121872

Algorithmic titration

Basal NEAR/2 bolus

BBI

Insulin NEAR/2 protocol

Sliding NEAR/2 scale

Intensive glucose control ‘glycemic control’:ti

‘glycaemic control’:ti

(intensive OR tight) NEAR/2 

(‘glycemic control’ OR ‘glycaemic 

control’)

‘intensive glucose lowering’
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 144 of 160

Concept Controlled Vocabulary Keywords/PubMed Concepts 

Macrovascular outcomes EMBASE

‘diabetic cardiomyopathy’/de

‘ischemic heart disease’/de

‘peripheral vascular disease’/de

Acute coronary events

CAD

Cardiovascular outcome*

Cerebrovascular accident*

CHF

Coronary artery disease

Heart attack*

Heart disease

Heart failure

Ischemic heart disease

Macrovascular complication*

MI 

Myocardial infarction

Peripheral vascular disease

Stroke*

Unstable angina

Mortality

Quality of life

QOL

Microvascular outcomes EMBASE

‘disease association’/de

‘disease course’/mj

‘diabetic angiopathy’/de

‘diabetic foot’/de

‘diabetic microangiopathy’/de

‘diabetic nephropathy’/de

‘diabetic neuropathy’/de

‘diabetic retinopathy’/de

‘microangiopathy’/de

‘kidney disease’/exp/mj

[includes chronic kidney disease and 

kidney failure]

‘neuropathy’/de

‘Retinopathy’/de

Chronic kidney disease

CMD

Coronary microvascular 

dysfunction

Diabetic nephropathy

Hypoglycem*

Hypoglycaem*

Macroalbuminuria

Microalbuminuris

Microvascular complication*

Nephropath*

Neuorpath*

Renal failure

Renal insufficiency

Retinopath*
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 145 of 160

Concept Controlled Vocabulary Keywords/PubMed Concepts 

Medical nutrition therapy EMBASE

‘nutrition’/exp

[Note: parent term for tree with diet and 

diet therapy. Includes terms for 

Mediterranean, Paleo and other specific 

diets]

‘caloric intake’/de

‘food intake’/de

‘Cereal’/de

‘Dairy product’/de

‘Drinking behavior’/de

‘Egg’/de

‘Legume’/de

‘Meat’/de

‘Red meat’/de

‘Smoking habit’/de

‘Tomato’/de

‘Vegetable’/de

‘Exercise’/de

Diet*

‘MNT’

‘Medical nutrition therapy’

Mediterranean* NEAR/2 diet*

‘MeDiet’

Nutrition*

‘ADA diet’

‘carb counting’

‘carbohydrate counting’

‘DASH’

‘Dutch Health Council diet’

Ketogenic

‘low carbohydrate’

‘low energy’

‘low fat’

‘low glycemic index’ 

‘low glycaemic index’

‘Nordic diet’

‘Paleo’

‘Vegan’

Specific trials:

MEDINA

MOLI-SANI study

Patient education EMBASE

‘Diabetes education’/de

‘Health education’/de

‘Health promotion’/de

‘Patient education’/de

Individual

One-on-one

One-to-one

Standard care

(patient* OR adult* OR client* 

OR participant* OR individual*) 

NEAR/3 (train* OR educat* OR 

teach* OR instruct* OR inform* 

OR counsel* OR empower*)

Self management EMBASE

‘blood glucose self-monitoring’/exp

‘Self care’/exp

Blood NEAR/2 (glucose OR sugar)

‘Disease management’

Self NEAR/4 (care OR efficacy* 

OR manag* OR monitor*)
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 146 of 160

Concept Controlled Vocabulary Keywords/PubMed Concepts 

Shared decision-making EMBASE

‘diabetic patient’/de

‘patient decision making’/de

‘patient participation’/de

‘clinical decision making’/de

‘decision making’/de

‘doctor patient relation’/de

‘interpersonal communication’/de

‘trust’/de

Choice*

‘choice behavior’

‘choice behaviour’

Choose*

‘clinical decision making’

Decision*

Decid*

‘decision making’

‘decision process’

Deliberat*

Goal NEAR/2 set*

Option*

Patient-centered

Patient NEAR/2 (preferenc* OR 

priorit*)

Patient NEAR/2 (shared OR 

sharing OR centered OR trust)

Priorit*

SDM

‘Multiple chronic conditions’

MCC

Multimorbid*

Reviewed related citations for 

PMIDs:

26645932

Utilization of a cloud-based 

diabetes management program 

for insulin initiation and titration 

enables collaborative decision 

making between healthcare 

providers and patients

26458383

Shared decision-making in 

diabetes care

26567256

Informed shared decision-making 

programme on the prevention of 

myocardial infarction in type 2 

diabetes: a randomized 

controlled trial
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 147 of 160

Concept Controlled Vocabulary Keywords/PubMed Concepts 

Telemedicine EMBASE

‘telehealth’/exp

‘health care’/exp

‘mass communication’/de

‘e-mail’/de

‘interactive voice response system’/de

‘internet’/de

‘mass medium’/de

‘mobile phone’/de

‘online system’/de

‘social media’/de

‘telephone’/de

‘text messaging’/de

‘videoconferencing’/de

‘wireless communication’/de

Telecare*

Teleconsult*

Teledermatol*

Telediagnos*

Telehealth*

Telehomecare*

Telemanag*

Telematics

Telemonitor*

Telenurs*

Telepathol*

Telepharm*

Telepsychiatr*

Telestroke

Telesupport

(tele OR remote) NEAR/2 (health 

OR care* OR diagnos* OR 

monitor* OR manag* OR 

consult* OR home* OR nurs* OR 

dermatol* OR pathol* OR 

pharmac* OR nurs* OR 

psychiatr* OR stroke OR support)

Bluetooth

Computer*

Email

‘e-mail’

Interactive*

Internet*

Phone*

SMS

Telecommunication*

Telephone*

Video*

Web*

Wireless
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 148 of 160

Appendix I: Acronym List

Abbreviation Definition

ACCORD Action to Control Cardiovascular Risk in Diabetes 

ADA American Diabetes Association

ADOPT A Diabetes Outcome Progression Trial 

ADVANCE Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled 

Evaluation

AGI alpha-glucosidase inhibitor

AHRQ Agency for Healthcare Research and Quality

AMI acute myocardial infarction 

AMP 5’ adenosine monophosphate-activated protein

ARR absolute risk reduction

ATP adenosine triphosphate

BMI body massindex

CGM continuous glucose monitor

CI confidence interval

CKD chronic kidney disease

CMS Centers for Medicare and Medicaid Services

COI conflict of interest

COPD chronic obstructive pulmonary disease 

CPG clinical practice guideline

CV coefficient of variation

CVD cardiovascular disease

DIGAMI Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction

DKA diabetic ketoacidosis

DM diabetes mellitus

DoD Department of Defense

DPP-4 dipeptidyl peptidase-4 

DSME diabetes self-management education 

DSMS diabetes self-management support

eAG estimated average glucose 

EBPWG Evidence-Based Practice Work Group 

eGFR estimated glomerular filtration rate

ESRD end stage renal disease 

FDA U.S. Food and Drug Administration

FPG fasting plasma glucose

GDM gestational diabetes mellitus

GI gastrointestinal

GLP-1 glucagon-like peptide-1 

GRADE Grading of Recommendations Assessment, Development and Evaluation 

HbA1c hemoglobin A1c
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 149 of 160

Abbreviation Definition

HDL-C high-density lipoprotein cholesterol

HHS U.S. Department of Health and Human Services

HR hazard ratio

HRSA Health Resources and Services Administration

IBGMS internet-based glucose monitoring system 

ICU intensive care unit

IFG impaired fasting glucose 

IGT impaired glucose tolerance 

KQ key question

LDL-C low-density lipoprotein cholesterol

MD mean difference

MDD major depressive disorder

MET metformin

MHS Military Health System

MI myocardial infarction

MNT medical nutrition therapy

MODY maturity onset diabetes of the young

N/A not applicable

NICE National Institute for Health and Care Excellence

NICE-SUGAR Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation

NIH National Institutes of Health

NPH neutral protamine Hagedorn

OGTT oral glucose tolerance testing 

OPTEMPO operations tempo

PBM Pharmacy Benefits Management program 

PICOTS population, intervention, comparison, outcome, timing and setting 

PPAR peroxisome proliferator-activated receptor

P&T Pharmacy and Therapeutics Committee 

QoL quality of life 

RCT randomized controlled trial

RDN registered dietitian nutritionist 

RN registered nurse 

SD standard deviation

SDM shared decision-making 

SGLT2 sodium glucose co-transporter 2 

SMBG self-monitoring of blood glucose 

SR systematic review

SU sulfonylurea 

SUD substance use disorder 

T1DM type 1 diabetes mellitus
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 150 of 160

Abbreviation Definition

T2DM type 2 diabetes mellitus

TIA transient ischemic attack 

TZD thiazolidinedione

UKPDS United Kingdom Prospective Diabetes Study 

U.S. United States of America 

USPSTF U.S. Preventive Services Task Force 

VA Department of Veterans Affairs 

VADT Veteran Affairs Diabetes Trial
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 151 of 160

References

1. U.S. Department of Veteran Affairs, Department of Defense. Guideline for guidelines. Veterans

Health Administration, Office of Quality & Performance, Evidence Review Subgroup; Revised

April 10, 2013.

2. Pogach LM, Brietzke SA, Cowan CL, et al. Development of evidence-based clinical practice

guidelines for diabetes: The Department of Veterans Affairs/Department of Defense Guidelines

Initiative. Diabetes Care. 2004;27(Suppl 2):b82-b89.

3. MedlinePlus. Prediabetes. 2016; https://medlineplus.gov/prediabetes.html. Accessed July 18,

2016.

4. Little RR, Rohlfing CL, Hanson S, et al. Effects of hemoglobin (Hb)E and HbD traits on

measurements of glycated Hb (HbA1c) by 23 methods. Clin Chem. Aug 2008;54(8):1277-1282.

5. Little RR, Rohlfing CL, Hanson SE, et al. The effect of increased fetal hemoglobin on seven

common HbA(1c) assay methods. Clinical chemistry. 2012;58(5):945-947.

6. Herman WH, Ma Y, Uwaifo G, et al. Differences in A1C by race and ethnicity among patients with

impaired glucose tolerance in the Diabetes Prevention Program. Diabetes Care.

2007;30(10):2453-2457.

7. American Diabetes Association. Standards of Medical Care in Diabetes—2016. Diabetes Care.

2016;39(Suppl 1: S1-S2).

8. Forouhi NG, Wareham NJ. Epidemiology of diabetes. Medicine. 2014;42(12):698-702.

9. Centers for Disease Control and Prevention. Number (in millions) of civilian, non-institutionalized

persons with diagnosed diabetes, United States, 1980-2014. 2015;

http://www.cdc.gov/diabetes/statistics/prev/national/figpersons.htm. Accessed July 19, 2016.

10. Centers for Disease Control and Prevention. 2014 National Diabetes Statistics Report. 2015;

http://www.cdc.gov/diabetes/data/statistics/2014statisticsreport.html. Accessed July 20, 2016.

11. Chao SY, Zarzabal LA, Walker SM, et al. Estimating diabetes prevalence in the Military Health

System population from 2006 to 2010. Mil Med. Sep 2013;178(9):986-993.

12. U.S. Department of Veterans Affairs. Close to 25 percent of VA patients have diabetes. 2015;

http://www.va.gov/health/NewsFeatures/20111115a.asp. Accessed December 3, 2015.

13. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care.

Revised 2010;33(Suppl 1):S62-S69.

14. American Diabetes Association. Statistics about diabetes. 2016;

http://www.diabetes.org/diabetes-basics/statistics/?referrer=https://www.google.com/.

Accessed July 20, 2016.

15. Andrews J, Guyatt G, Oxman AD, et al. GRADE guidelines: 14. Going from evidence to

recommendations: The significance and presentation of recommendations. J Clin Epidemiol. Jul

2013;66(7):719-725.

16. Newberry SJ, Ahmadzai N, Motala A, et al. Surveillance and identification of signals for updating

systematic reviews: Implementation and early experience. Rockville, MD: Agency for Healthcare

Research and Quality; 2013.

17. Guirguis-Blake J, Calonge N, Miller T, Siu A, Teutsch S, Whitlock E. Current processes of the U.S.

Preventive Services Task Force: Refining evidence-based recommendation development. Ann

Intern Med. Jul 17 2007;147(2):117-122.

18. National Institute for Health and Care Excellence. The guidelines manual. London: National

Institute for Health and Care Excellence;2012.

https://www.nice.org.uk/process/pmg6/chapter/introduction.

19. Martinez Garcia L, McFarlane E, Barnes S, Sanabria AJ, Alonso-Coello P, Alderson P. Updated

recommendations: An assessment of NICE clinical guidelines. Implement Sci. 2014;9:72.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 152 of 160

20. White CM, Ip S, McPheeters M, et al. Using existing systematic reviews to replace de novo

processes in conducting comparative effectiveness reviews. Rockville, MD: Agency for Healthcare

Research and Quality; 2008.

21. Clinical practice guidelines we can trust. Washington, DC: National Academies Press;2011.

22. Schunemann HJ, Fretheim A, Oxman AD. Improving the use of research evidence in guideline

development: 10. Integrating values and consumer involvement. Health Res Policy Syst.

2006;4:22.

23. Institute of Medicine. Crossing the quality chasm: A new health system for the 21st century.

Washington, DC: National Academies Press; 2001.

24. Kirkman MS, Briscoe VJ, Clark N, et al. Diabetes in older adults: A consensus report. J Am Geriatr

Soc. Dec 2012;60(12):2342-2356.

25. U.S. Army Medical Department. VA/DoD Evidence-based Practice. Shared decision-making. A

guide for busy clinicians. 2012;

https://www.qmo.amedd.army.mil/QMOCPGShopCart/proddetail.asp?prod=All-005. Accessed

March 17, 2017.

26. Agency for Healthcare Research and Quality. The SHARE approach. 2017;

https://www.ahrq.gov/professionals/education/curriculumtools/shareddecisionmaking/index.html. Accessed March 17, 2017.

27. Bertakis KD, Azari R. Patient-centered care is associated with decreased health care utilization. J

Am Board Fam Med. May-Jun 2011;24(3):229-239.

28. Robinson JH, Callister LC, Berry JA, Dearing KA. Patient-centered care and adherence: Definitions

and applications to improve outcomes. J Am Acad Nurse Pract. Dec 2008;20(12):600-607.

29. Society for Medical Decision Making Committee on Standardization of Clinical Algorithms.

Proposal for clinical algorithm standards. Med Decis Making. Apr-Jun 1992;12(2):149-154.

30. Hsu WC, Lau KH, Huang R, et al. Utilization of a cloud-based diabetes management program for

insulin initiation and titration enables collaborative decision making between healthcare

providers and patients. Diabetes Technol Ther. Feb 2016;18(2):59-67.

31. Branda ME, LeBlanc A, Shah ND, et al. Shared decision making for patients with type 2 diabetes:

A randomized trial in primary care. BMC Health Serv Res. 2013;13:301.

32. Buhse S, Muhlhauser I, Heller T, et al. Informed shared decision-making programme on the

prevention of myocardial infarction in type 2 diabetes: A randomised controlled trial. BMJ Open.

2015;5(11):e009116.

33. Mullan RJ, Montori VM, Shah ND, et al. The diabetes mellitus medication choice decision aid: A

randomized trial. Arch Intern Med. Sep 28 2009;169(17):1560-1568.

34. Steinsbekk A, Rygg LO, Lisulo M, Rise MB, Fretheim A. Group based diabetes self-management

education compared to routine treatment for people with type 2 diabetes mellitus. A systematic

review with meta-analysis. BMC Health Serv Res. 2012;12:213.

35. Kim MT, Kim KB, Huh B, et al. The effect of a community-based self-help intervention. Am J Prev

Med. Nov 2015;49(5):726-737.

36. Cohen LB, Taveira TH, Khatana SA, Dooley AG, Pirraglia PA, Wu WC. Pharmacist-led shared

medical appointments for multiple cardiovascular risk reduction in patients with type 2

diabetes. Diabetes Educ. Nov-Dec 2011;37(6):801-812.

37. Crowley MJ, Powers BJ, Olsen MK, et al. The cholesterol, hypertension, and glucose education

(CHANGE) study: Results from a randomized controlled trial in African Americans with diabetes.

Am Heart J. Jul 2013;166(1):179-186.

38. McMahon GT, Fonda SJ, Gomes HE, Alexis G, Conlin PR. A randomized comparison of online- and

telephone-based care management with internet training alone in adult patients with poorly

controlled type 2 diabetes. Diabetes Technol Ther. Nov 2012;14(11):1060-1067.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 153 of 160

39. Sperl-Hillen J, Beaton S, Fernandes O, et al. Comparative effectiveness of patient education

methods for type 2 diabetes: A randomized controlled trial. Arch Intern Med.

2011;171(22):2001-2010.

40. Pillay J, Armstrong MJ, Butalia S, et al. Behavioral programs for type 2 diabetes mellitus: A

systematic review and network meta-analysis. Ann Intern Med. Dec 2015;163(11):848-860.

41. Duke SA, Colagiuri S, Colagiuri R. Individual patient education for people with type 2 diabetes

mellitus. Cochrane Database Syst Rev. 2009(1):Cd005268.

42. Forjuoh SN, Bolin JN, Huber JC, Jr., et al. Behavioral and technological interventions targeting

glycemic control in a racially/ethnically diverse population: A randomized controlled trial. BMC

Public Health. 2014;14:71.

43. Pal K, Eastwood SV, Michie S, et al. Computer-based diabetes self-management interventions for

adults with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2013(3):Cd008776.

44. Tang PC, Overhage JM, Chan AS, et al. Online disease management of diabetes: Engaging and

motivating patients online with enhanced resources-diabetes (EMPOWER-D), a randomized

controlled trial. J Am Med Inform Assoc. May 2013;20(3):526-534.

45. Tildesley HD, Mazanderani AB, Chan JHM, Ross SA. Efficacy of A1C reduction using internet

intervention in patients with type 2 diabetes treated with insulin. Can J Diabetes.

2011;35(3):250-253.

46. Luchsinger JA, Palmas W, Teresi JA, et al. Improved diabetes control in the elderly delays global

cognitive decline. J Nutr Health Aging. Jun 2011;15(6):445-449.

47. Holbrook A, Thabane L, Keshavjee K, et al. Individualized electronic decision support and

reminders to improve diabetes care in the community: COMPETE II randomized trial. CMAJ. Jul

2009;181(1-2):37-44.

48. Wakefield BJ, Koopman RJ, Keplinger LE, et al. Effect of home telemonitoring on glycemic and

blood pressure control in primary care clinic patients with diabetes. Telemed J E Health. Mar

2014;20(3):199-205.

49. Pacaud D, Kelley H, Downey AM, Chiasson M. Successful delivery of diabetes self-care education

and follow-up through ehealth media. Can J Diabetes. Oct 2012;36(5):257-262.

50. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: An emerging consensus on rating quality of

evidence and strength of recommendations. BMJ. Apr 2008;336(7650):924-926.

51. Guyatt G, Oxman AD, Akl EA, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles

and summary of findings tables. J Clin Epidemiol. Apr 2011;64(4):383-394.

52. Higgins J, Green S. Cochrane handbook for systematic reviews of interventions. London: The

Cochrane Collaboration. 2011;5.1.0.

53. U.K. Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with

sulphonylureas or insulin compared with conventional treatment and risk of complications in

patients with type 2 diabetes (UKPDS 33). Lancet. Sep 1998;352(9131):837-853.

54. Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and

microvascular complications of type 2 diabetes (UKPDS 35): Prospective observational study.

BMJ. Aug 2000;321(7258):405-412.

55. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose

control in type 2 diabetes. N Engl J Med. Oct 2008;359(15):1577-1589.

56. ACCORD Study Group. Nine-year effects of 3.7 years of intensive glycemic control on

cardiovascular outcomes. Diabetes Care. May 2016;39(5):701-708.

57. Hayward RA, Reaven PD, Wiitala WL, et al. Follow-up of glycemic control and cardiovascular

outcomes in type 2 diabetes. N Engl J Med. Jun 2015;372(23):2197-2206.

58. Zoungas S, Chalmers J, Neal B, et al. Follow-up of blood-pressure lowering and glucose control in

type 2 diabetes. N Engl J Med. Oct 2014;371(15):1392-1406.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 154 of 160

59. Hemmingsen B, Lund SS, Gluud C, et al. Targeting intensive glycaemic control versus targeting

conventional glycaemic control for type 2 diabetes mellitus. Cochrane Database Syst Rev.

2011(6):Cd008143.

60. Hasan R, Firwana B, Elraiyah T, et al. A systematic review and meta-analysis of glycemic control

for the prevention of diabetic foot syndrome. J Vasc Surg. Feb 2016;63(Suppl 2):22S-28S.e21-22.

61. Callaghan BC, Little AA, Feldman EL, Hughes RA. Enhanced glucose control for preventing and

treating diabetic neuropathy. Cochrane Database Syst Rev. 2012(6):Cd007543.

62. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type

2 diabetes. N Engl J Med. Jul 2016;375(4):311-322.

63. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in

type 2 diabetes. N Engl J Med. Nov 2015;373(22):2117-2128.

64. U.K. Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with

metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet.

Sep 1998;352(9131):854-865.

65. Sacks DB, Arnold M, Bakris GL, et al. Executive summary: Guidelines and recommendations for

laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem. Jun

2011;57(6):793-798.

66. Wolffenbuttel BH, Herman WH, Gross JL, Dharmalingam M, Jiang HH, Hardin DS. Ethnic

differences in glycemic markers in patients with type 2 diabetes. Diabetes Care. Oct

2013;36(10):2931-2936.

67. Ruud KL, Leblanc A, Mullan RJ, et al. Lessons learned from the conduct of a multisite cluster

randomized practical trial of decision aids in rural and suburban primary care practices. Trials.

Aug 2013;14:267.

68. Radin MS. Pitfalls in hemoglobin A1c measurement: When results may be misleading. J Gen

Intern Med. Feb 2014;29(2):388-394.

69. Cohen RM, Franco RS, Khera PK, et al. Red cell life span heterogeneity in hematologically normal

people is sufficient to alter HbA1c. Blood. Nov 2008;112(10):4284-4291.

70. Smith EP, Cohen RM. Physiologic concepts that may revise the interpretation and implications of

HbA1C in clinical medicine: An American perspective. J Diabetes Sci Technol. Feb 2015;9(3):696-

700.

71. English E, Idris I, Smith G, Dhatariya K, Kilpatrick ES, John WG. The effect of anaemia and

abnormalities of erythrocyte indices on HbA1c analysis: A systematic review. Diabetologia. Jul

2015;58(7):1409-1421.

72. Goldstein D, Little R, Lorenz R, Malone J, Nathan D, Peterson C. Tests of glycemia in diabetes.

Diabetes Care. Jun 1995;18:896-909.

73. Kim IY, Kim MJ, Lee DW, et al. Glycated albumin is a more accurate glycemic indicator than

hemoglobin A1c in diabetic patients with pre-dialysis chronic kidney disease. Nephrology

(Carlton). May 2015.

74. Viberti G, Lachin J, Holman R, et al. A diabetes outcome progression trial (ADOPT): Baseline

characteristics of type 2 diabetic patients in North America and Europe. Diabet Med. Dec

2006;23(12):1289-1294.

75. Herman WH. Are there clinical implications of racial differences in HbA1c? Yes, to not consider

can do great harm! Diabetes Care. Aug 2016;39(8):1458-1461.

76. Selvin E. Are there clinical implications of racial differences in HbA1c? A difference, to be a

difference, must make a difference. Diabetes Care. Aug 2016;39(8):1462-1467.

77. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment

of diabetes on the development and progression of long-term complications in insulindependent diabetes mellitus. N Engl J Med. Sep 1993;329(14):977-986.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 155 of 160

78. The Diabetes Control and Complications Trial Research Group. The relationship of glycemic

exposure (HbA1c) to the risk of development and progression of retinopathy in the diabetes

control and complications trial. Diabetes. Aug 1995;44(8):968-983.

79. Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans

with type 2 diabetes. N Engl J Med. Jan 2009;360(2):129-139.

80. The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose

lowering in type 2 diabetes. N Engl J Med. Jun 2008;358(24):2545-2559.

81. The ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in

patients with type 2 diabetes. N Engl J Med. Jun 2008;358(24):2560-2572.

82. Gerstein HC, Miller ME, Ismail-Beigi F, et al. Effects of intensive glycaemic control on ischaemic

heart disease: Analysis of data from the randomised, controlled accord trial. Lancet. Nov

2014;384(9958):1936-1941.

83. Seaquist ER, Anderson J, Childs B, et al. Hypoglycemia and diabetes: A report of a workgroup of

the American diabetes association and The Endocrine Society. Diabetes Care. 2013.

84. ORIGIN Trial Investigators. Predictors of nonsevere and severe hypoglycemia during glucoselowering treatment with insulin glargine or standard drugs in the ORIGIN trial. Diabetes Care.

Jan 2015;38(1):22-28.

85. Bruderer SG, Bodmer M, Jick SS, Bader G, Schlienger RG, Meier CR. Incidence of and risk factors

for severe hypoglycaemia in treated type 2 diabetes mellitus patients in the UK--a nested casecontrol analysis. Diabetes Obes Metab. Sep 2014;16(9):801-811.

86. Gorst C, Kwok CS, Aslam S, et al. Long-term glycemic variability and risk of adverse outcomes: A

systematic review and meta-analysis. Diabetes Care. Dec 2015;38(12):2354-2369.

87. Prentice JC, Pizer SD, Conlin PR. Identifying the independent effect of HbA1c variability on

adverse health outcomes in patients with type 2 diabetes. Diabet Med. Jun 2016.

88. Colagiuri R, Eigenmann CA. A national consensus on outcomes and indicators for diabetes

patient education. Diabet Med. Apr 2009;26(4):442-446.

89. Corabian P, Harstall C. Patient diabetes education in the management of adult type 2 diabetes.

Health Technology Assessment. HA 23: Series A Edmonton: Alberta Heritage Foundation for

Medical Research (AHFMR); 2001.

90. Davies MJ, Heller S, Skinner TC, et al. Effectiveness of the diabetes education and self

management for ongoing and newly diagnosed (DESMOND) programme for people with newly

diagnosed type 2 diabetes: Cluster randomised controlled trial. BMJ Dec 2008;336(7642):491-

495.

91. Franz MJ, Monk A, Barry B, et al. Effectiveness of medical nutrition therapy provided by

dietitians in the management of non-insulin-dependent diabetes mellitus: A randomized,

controlled clinical trial. J Am Diet Assoc. Sep 1995;95(9):1009-1017.

92. Ajala O, English P, Pinkney J. Systematic review and meta-analysis of different dietary

approaches to the management of type 2 diabetes. Am J Clin Nutr. Mar 2013;97(3):505-516.

93. Rock CL, Flatt SW, Pakiz B, et al. Weight loss, glycemic control, and cardiovascular disease risk

factors in response to differential diet composition in a weight loss program in type 2 diabetes:

A randomized controlled trial. Diabetes Care. Jun 2014;37(6):1573-1580.

94. Huo R, Du T, Xu Y, et al. Effects of Mediterranean-style diet on glycemic control, weight loss and

cardiovascular risk factors among type 2 diabetes individuals: A meta-analysis. Eur J Clin Nutr.

Nov 2015;69(11):1200-1208.

95. Esposito K, Maiorino MI, Bellastella G, Chiodini P, Panagiotakos D, Giugliano D. A journey into a

Mediterranean diet and type 2 diabetes: A systematic review with meta-analyses. BMJ Open.

2015;5(8):e008222.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 156 of 160

96. Tay J, Luscombe-Marsh ND, Thompson CH, et al. A very low-carbohydrate, low-saturated fat diet

for type 2 diabetes management: A randomized trial. Diabetes Care. Nov 2014;37(11):2909-

2918.

97. Fabricatore AN, Wadden TA, Ebbeling CB, et al. Targeting dietary fat or glycemic load in the

treatment of obesity and type 2 diabetes: A randomized controlled trial. Diabetes Res Clin Pract.

Apr 2011;92(1):37-45.

98. Yancy WS, Jr., Foy M, Chalecki AM, Vernon MC, Westman EC. A low-carbohydrate, ketogenic

diet to treat type 2 diabetes. Nutr Metab (Lond). Dec 2005;2:34.

99. Pedersen E, Jesudason DR, Clifton PM. High protein weight loss diets in obese subjects with type

2 diabetes mellitus. Nutr Metab Cardiovasc Dis. May 2014;24(5):554-562.

100. Finfer S, Chittock DR, Su SY, et al. Intensive versus conventional glucose control in critically ill

patients. N Engl J Med. Mar 2009;360(13):1283-1297.

101. Brunkhorst FM, Engel C, Bloos F, et al. Intensive insulin therapy and pentastarch resuscitation in

severe sepsis. N Engl J Med. Jan 2008;358(2):125-139.

102. Reinhart K, Brunkhorst FM, Engel C, et al. [Study protocol of the VISEP study. Response of the

SepNet study group]. Anaesthesist. Jul 2008;57(7):723-728.

103. Gandhi GY, Murad MH, Flynn DN, et al. Effect of perioperative insulin infusion on surgical

morbidity and mortality: Systematic review and meta-analysis of randomized trials. Mayo Clin

Proc. Apr 2008;83(4):418-430.

104. Griesdale DE, de Souza RJ, van Dam RM, et al. Intensive insulin therapy and mortality among

critically ill patients: A meta-analysis including NICE-sugar study data. CMAJ. Apr

2009;180(8):821-827.

105. Kalfon P, Le Manach Y, Ichai C, et al. Severe and multiple hypoglycemic episodes are associated

with increased risk of death in ICU patients. Crit Care. 2015;19:153.

106. Pittas AG, Siegel RD, Lau J. Insulin therapy for critically ill hospitalized patients: A meta-analysis

of randomized controlled trials. Arch Intern Med. Oct 2004;164(18):2005-2011.

107. Patel AH, Pittas AG. Does glycemic control with insulin therapy play a role for critically ill

patients in hospital? CMAJ. Mar 2006;174(7):917-918.

108. Kansagara D, Wolf F, Freeman M, Helfand M. VA Evidence-based Synthesis Program Reports.

Management of Inpatient Hyperglycemia: A Systematic Review. Washington, DC: Department of

Veterans Affairs 2008.

109. Malmberg K. Prospective randomised study of intensive insulin treatment on long term survival

after acute myocardial infarction in patients with diabetes mellitus. DIGAMI (diabetes mellitus,

insulin glucose infusion in acute myocardial infarction) Study Group. BMJ. May

1997;314(7093):1512-1515.

110. Malmberg K, Ryden L, Wedel H, et al. Intense metabolic control by means of insulin in patients

with diabetes mellitus and acute myocardial infarction (DIGAMI 2): Effects on mortality and

morbidity. Eur Heart J. Apr 2005;26(7):650-661.

111. Umpierrez GE, Smiley D, Jacobs S, et al. Randomized study of basal-bolus insulin therapy in the

inpatient management of patients with type 2 diabetes undergoing general surgery (RABBIT 2

surgery). Diabetes Care. Feb 2011;34(2):256-261.

112. Umpierrez GE, Smiley D, Zisman A, et al. Randomized study of basal-bolus insulin therapy in the

inpatient management of patients with type 2 diabetes (RABBIT 2 trial). Diabetes Care. Sep

2007;30(9):2181-2186.

113. Haw JS, Farrokhi F, Smiley D, et al. Comparison of basal insulin regimens on glycemic variability

in noncritically ill patients with type 2 diabetes. Endocr Pract. Dec 2015;21(12):1333-1343.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 157 of 160

114. Vellanki P, Bean R, Oyedokun FA, et al. Randomized controlled trial of insulin supplementation 

for correction of bedtime hyperglycemia in hospitalized patients with type 2 diabetes. Diabetes 

Care. Apr 2015;38(4):568-574.

115. Bellido V, Suarez L, Rodriguez MG, et al. Comparison of basal-bolus and premixed insulin 

regimens in hospitalized patients with type 2 diabetes. Diabetes Care. Dec 2015;38(12):2211-

2216.

116. Umpierrez GE, Hor T, Smiley D, et al. Comparison of inpatient insulin regimens with detemir plus 

aspart versus neutral protamine hagedorn plus regular in medical patients with type 2 diabetes. 

J Clin Endocrinol Metab. Feb 2009;94(2):564-569.

117. Umpierrez GE, Smiley D, Hermayer K, et al. Randomized study comparing a basal-bolus with a 

basal plus correction insulin regimen for the hospital management of medical and surgical 

patients with type 2 diabetes: Basal plus trial. Diabetes Care. Aug 2013;36(8):2169-2174.

118. Powers MA, Bardsley J, Cypress M, et al. Diabetes self-management education and support in 

type 2 diabetes: A joint position statement of the American diabetes association, the American 

association of diabetes educators, and the Academy of Nutrition and Dietetics. Diabetes Care. 

Jul 2015;38(7):1372-1382.

119. Healy SJ, Black D, Harris C, Lorenz A, Dungan KM. Inpatient diabetes education is associated with 

less frequent hospital readmission among patients with poor glycemic control. Diabetes Care. 

Oct 2013;36(10):2960-2967.

120. Wexler DJ, Beauharnais CC, Regan S, Nathan DM, Cagliero E, Larkin ME. Impact of inpatient 

diabetes management, education, and improved discharge transition on glycemic control 12 

months after discharge. Diabetes Res Clin Pract. Nov 2012;98(2):249-256.

121. Shah M, Norwood CA, Farias S, Ibrahim S, Chong PH, Fogelfeld L. Diabetes transitional care from 

inpatient to outpatient setting: Pharmacist discharge counseling. J Pharm Pract. Apr 

2013;26(2):120-124.

122. Expert Committee on the Diagnosis and Clasification of Diabetes Mellitus. American diabetes 

association: Clinical practice recommendations 2002. Diabetes Care. Jan 2002;25 Suppl 1:S1-

147.

123. Mayfield JA, Reiber GE, Sanders LJ, Janisse D, Pogach LM. Preventive foot care in people with 

diabetes. Diabetes Care. Dec 1998;21(12):2161-2177.

124. Mayfield JA, Reiber GE, Nelson RG, Greene T. Do foot examinations reduce the risk of diabetic 

amputation? J Fam Pract. Jun 2000;49(6):499-504.

125. Carrington AL, Abbott CA, Griffiths J, et al. Peripheral vascular and nerve function associated 

with lower limb amputation in people with and without diabetes. Clin Sci (Lond). Sep 

2001;101(3):261-266.

126. Orchard TJ, Strandness DE, Jr. Assessment of peripheral vascular disease in diabetes. Report and 

recommendations of an international workshop sponsored by the American heart association 

and the American diabetes association 18-20 September 1992, New Orleans, Louisiana. Diabetes 

Care. Aug 1993;16(8):1199-1209.

127. Brodsky JW, Schneidler C. Diabetic foot infections. Orthop Clin North Am. Jul 1991;22(3):473-

489.

128. Caputo GM, Cavanagh PR, Ulbrecht JS, Gibbons GW, Karchmer AW. Assessment and 

management of foot disease in patients with diabetes. N Engl J Med. Sep 1994;331(13):854-860.

129. Eckman MH, Greenfield S, Mackey WC, et al. Foot infections in diabetic patients. Decision and 

cost-effectiveness analyses. JAMA. Mar 1995;273(9):712-720.

130. Reiber G, Boyko E, Smith D. Lower extremity foot ulcers and amputations in diabetes. Diabetes 

in america. 2nd ed. Baltimore, MD: National Institute of Diabetes and Digestive and Kidney 

Diseases, National Institutes of Health 1995:NIH Publication No. 95-1468.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 158 of 160

131. Giacalone VF. Phenol matricectomy in patients with diabetes. J Foot Ankle Surg. Jul-Aug 

1997;36(4):264-267; discussion 328.

132. Conlin PR, Asefzadeh B, Pasquale LR, Selvin G, Lamkin R, Cavallerano AA. Accuracy of a 

technology-assisted eye exam in evaluation of referable diabetic retinopathy and concomitant 

ocular diseases. Br J Ophthalmol. Dec 2015;99(12):1622-1627.

133. Whited JD. Accuracy and reliability of teleophthalmology for diagnosing diabetic retinopathy 

and macular edema: A review of the literature. Diabetes Technol Ther. Feb 2006;8(1):102-111.

134. Morrison JL, Hodgson LA, Lim LL, Al-Qureshi S. Diabetic retinopathy in pregnancy: A review. Clin 

Exp Ophthalmol. May 2016;44(4):321-334.

135. Stratton IM, Kohner EM, Aldington SJ, et al. UKPDS 50: Risk factors for incidence and progression 

of retinopathy in type II diabetes over 6 years from diagnosis. Diabetologia. Feb 2001;44(2):156-

163.

136. Voutilainen-Kaunisto R, Terasvirta M, Uusitupa M, Niskanen L. Maculopathy and visual acuity in 

newly diagnosed type 2 diabetic patients and non-diabetic subjects: A 10-year follow-up study. 

Acta Ophthalmol Scand. Apr 2001;79(2):163-168.

137. Vijan S, Hofer TP, Hayward RA. Cost-utility analysis of screening intervals for diabetic 

retinopathy in patients with type 2 diabetes mellitus. JAMA. Feb 2000;283(7):889-896.

138. Kitzmiller JL, Block JM, Brown FM, et al. Managing preexisting diabetes for pregnancy: Summary 

of evidence and consensus recommendations for care. Diabetes Care. May 2008;31(5):1060-

1079.

139. Lexi-Comp, Inc. Lexi-drugs. http://online.lexi.com/action/home. Accessed November 23, 2016.

140. Bolen S, Feldman L, Vassy J, et al. Systematic review: Comparative effectiveness and safety of 

oral medications for type 2 diabetes mellitus. Ann Intern Med. Sep 2007;147(6):386-399.

141. Bennett WL, Maruthur NM, Singh S, et al. Comparative effectiveness and safety of medications 

for type 2 diabetes: An update including new drugs and 2-drug combinations. Ann Intern Med. 

May 3 2011;154(9):602-613.

142. Maruthur NM, Tseng E, Hutfless S, et al. Diabetes medications as monotherapy or metforminbased combination therapy for type 2 diabetes: A systematic review and meta-analysis. Ann 

Intern Med. Jun 2016;164(11):740-751.

143. Bolen S, Tseng E, Hutfless S, et al. AHRQ comparative effectiveness reviews. Diabetes 

medications for adults with type 2 diabetes: An update. Rockville (MD): Agency for Healthcare 

Research and Quality (US); 2016.

144. Umpierrez G, Tofe Povedano S, Perez Manghi F, Shurzinske L, Pechtner V. Efficacy and safety of 

dulaglutide monotherapy versus metformin in type 2 diabetes in a randomized controlled trial 

(AWARD-3). Diabetes Care. Aug 2014;37(8):2168-2176.

145. Russell-Jones D, Cuddihy RM, Hanefeld M, et al. Efficacy and safety of exenatide once weekly 

versus metformin, pioglitazone, and sitagliptin used as monotherapy in drug-naive patients with 

type 2 diabetes (DURATION-4): A 26-week double-blind study. Diabetes Care. Feb 

2012;35(2):252-258.

146. Garber A, Henry R, Ratner R, et al. Liraglutide versus glimepiride monotherapy for type 2 

diabetes (LEAD-3 Mono): A randomised, 52-week, phase III, double-blind, parallel-treatment 

trial. Lancet. Feb 2009;373(9662):473-481.

147. Roden M, Weng J, Eilbracht J, et al. Empagliflozin monotherapy with sitagliptin as an active 

comparator in patients with type 2 diabetes: A randomised, double-blind, placebo-controlled, 

phase 3 trial. Lancet Diabetes Endocrinol. Nov 2013;1(3):208-219.

148. Sun F, Wu S, Guo S, et al. Impact of GLP-1 receptor agonists on blood pressure, heart rate and 

hypertension among patients with type 2 diabetes: A systematic review and network metaanalysis. Diabetes Res Clin Pract. Oct 2015;110(1):26-37.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 159 of 160

149. Lee CM, Woodward M, Colagiuri S. Triple therapy combinations for the treatment of type 2

diabetes - a network meta-analysis. Diabetes Res Clin Pract. Jun 2016;116:149-158.

150. Derosa G, Cicero AF, Franzetti IG, et al. A comparison between sitagliptin or glibenclamide in

addition to metformin + pioglitazone on glycaemic control and beta-cell function: The triple oral

therapy. Diabet Med. Jul 2013;30(7):846-854.

151. Liu SC, Chien KL, Wang CH, Chen WC, Leung CH. Efficacy and safety of adding pioglitazone or

sitagliptin to patients with type 2 diabetes insufficiently controlled with metformin and a

sulfonylurea. Endocr Pract. Nov-Dec 2013;19(6):980-988.

152. Schernthaner G, Gross JL, Rosenstock J, et al. Canagliflozin compared with sitagliptin for patients

with type 2 diabetes who do not have adequate glycemic control with metformin plus

sulfonylurea: A 52-week randomized trial. Diabetes Care. Sep 2013;36(9):2508-2515.

153. Home PD, Shamanna P, Stewart M, et al. Efficacy and tolerability of albiglutide versus placebo or

pioglitazone over 1 year in people with type 2 diabetes currently taking metformin and

glimepiride: HARMONY 5. Diabetes Obes Metab. Feb 2015;17(2):179-187.

154. White RD. The treat-to-target A1C approach to control type 2 diabetes and prevent

complications. Adv Ther. May-Jun 2007;24(3):545-559.

155. Eng C, Kramer CK, Zinman B, Retnakaran R. Glucagon-like peptide-1 receptor agonist and basal

insulin combination treatment for the management of type 2 diabetes: A systematic review and

meta-analysis. Lancet. Dec 2014;384(9961):2228-2234.

156. Lantus [package insert]. Bridgewater, NJ: Sanofi Inc.; July 2015.

157. Tresiba [package insert]. Plainsboro, NJ: Novo Nordisk Inc.; September 2015.

158. Humalog [package insert]. Indianapolis, IN: Eli Lilly & Co.; May 2015.

159. Novolog [package insert]. Plainsboro, NJ: Novo Nordisk Inc.; February 2015.

160. Apidra [package insert]. Bridgewater, NJ: Sanofi Inc.; February 2015.

161. Levemir [package insert]. Plainsboro, NJ: Novo Nordisk Inc.; February 2015.

162. Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in

type 2 diabetes. N Engl J Med. Jul 2015;373(3):232-242.

163. Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients

with type 2 diabetes mellitus. N Engl J Med. Oct 2013;369(14):1317-1326.

164. White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in patients with

type 2 diabetes. N Engl J Med. Oct 2013;369(14):1327-1335.

165. Fu AZ, Johnston SS, Ghannam A, et al. Association between hospitalization for heart failure and

dipeptidyl peptidase 4 inhibitors in patients with type 2 diabetes: An observational Study.

Diabetes Care. May 2016;39(5):726-734.

166. Toh S, Hampp C, Reichman ME, et al. Risk for hospitalized heart failure among new users of

saxagliptin, sitagliptin, and other antihyperglycemic drugs: A retrospective cohort Study. Ann

Intern Med. Jun 7 2016;164(11):705-714.

167. Marx N, Rosenstock J, Kahn SE, et al. Design and baseline characteristics of the cardiovascular

outcome trial of linagliptin versus glimepiride in type 2 diabetes (CAROLINA(R)). Diab Vasc Dis

Res. May 2015;12(3):164-174.

168. Dormandy JA, Charbonnel B, Eckland DJ, et al. Secondary prevention of macrovascular events in

patients with type 2 diabetes in the PROactive Study (prospective pioglitazone clinical trial in

macrovascular events): A randomised controlled trial. Lancet. Oct 2005;366(9493):1279-1289.

169. Kernan WN, Viscoli CM, Furie KL, et al. Pioglitazone after ischemic stroke or transient ischemic

attack. N Engl J Med. Apr 2016;374(14):1321-1331.

170. Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute

coronary syndrome. N Engl J Med. Dec 2015;373(23):2247-2257.
VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

April 2017 Page 160 of 160

171. Holman RR, Bethel MA, George J, et al. Rationale and design of the exenatide Study of

cardiovascular event lowering (EXSCEL) trial. Am Heart J. Apr 2016;174:103-110.

172. Ahren B, Johnson SL, Stewart M, et al. HARMONY 3: 104-week randomized, double-blind,

placebo- and active-controlled trial assessing the efficacy and safety of albiglutide compared

with placebo, sitagliptin, and glimepiride in patients with type 2 diabetes taking metformin.

Diabetes Care. Aug 2014;37(8):2141-2148.

173. Ferdinand KC, Botros FT, Atisso CM, Sager PT. Cardiovascular safety for once-weekly dulaglutide

in type 2 diabetes: A pre-specified meta-analysis of prospectively adjudicated cardiovascular

events. Cardiovasc Diabetol. Feb 2016;15:38.

174. Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with

type 2 diabetes. N Engl J Med. Sep 2016.

175. Neal B, Perkovic V, de Zeeuw D, et al. Rationale, design, and baseline characteristics of the

canagliflozin cardiovascular assessment Study (CANVAS)--a randomized placebo-controlled trial.

Am Heart J. Aug 2013;166(2):217-223.e211.

176. AstraZeneca. Multicenter trial to evaluate the effect of dapagliflozin on the incidence of

cardiovascular events (DECLARE-TIMI58). NLM Identifier: NCT01730534. Vol 2017. Bethesda, MD

clinicaltrials.gov: https://clinicaltrials.gov/show/NCT01730534; 2012.

177. Agency for Health Research and Quality. The Effective Health Care Program stakeholder guide

Appendix D: Research questions & PICO(TS) 2011.

http://www.ahrq.gov/clinic/epcpartner/stakeholderguide/.

178. Andrews JC, Schunemann HJ, Oxman AD, et al. GRADE guidelines: 15. Going from evidence to

recommendation-determinants of a recommendation's direction and strength. J Clin Epidemiol.

Jul 2013;66(7):726-735.