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## Complete Summary

#### GUIDELINE TITLE

Clinical guideline for pharmacological management of type 2 diabetes.

#### BIBLIOGRAPHIC SOURCE(S)

Joslin Diabetes Center. Clinical guideline for pharmacological
management of type 2 diabetes. Boston (MA): Joslin Diabetes Center; 2007
Jan 12. 9 p. \[91 references\]

#### GUIDELINE STATUS

This is the current release of the guideline.

This guideline will be reviewed periodically and modified to reflect
changes in clinical practice and available pharmacological information.

### \*\* REGULATORY ALERT \*\*

#### FDA WARNING/REGULATORY ALERT

**Note from the National Guideline Clearinghouse**: This guideline
references a drug(s) for which important revised regulatory and/or
warning information has been released.

-   [April 10, 2008, Exubera (insulin
    inhalation)](http://www.fda.gov/medwatch/safety/2008/safety08.htm#exubera):
    Pfizer informed healthcare professionals and patients of updated
    safety information in the WARNINGS section of prescribing
    information for Exubera. This warning relates to a small number of
    primary lung malignancies that have been discovered in users of
    Exubera in clinical trials and post-marketing reports.

-   [February 26, 2008, Avandia
    (rosiglitazone)](http://www.fda.gov/medwatch/safety/2008/safety08.htm#Avandia):
    A new Medication Guide for Avandia must be provided with each
    prescription that is dispensed due to the U.S. Food and Drug
    Administration\'s (FDA\'s) determination that this medication could
    pose a serious and significant public health concern.

-   [November 14, 2007, Avandia
    (rosiglitazone)](http://www.fda.gov/medwatch/safety/2007/safety07.htm#Avandia2):
    New information has been added to the existing boxed warning in
    Avandia\'s prescribing information about potential increased risk
    for heart attacks.

-   [October 16, 2007, Byetta
    (exenatide)](http://www.fda.gov/medwatch/safety/2007/safety07.htm#Byetta):
    Amylin Pharmaceuticals, Inc. has agreed to include information about
    acute pancreatitis in the PRECAUTIONS section of the product label.

-   [August 14, 2007, Thiazolidinedione class of antidiabetic
    drugs](http://www.fda.gov/medwatch/safety/2007/safety07.htm#rosi_pio):
    Addition of a boxed warning to the updated label of the entire
    thiazolidinedione class of antidiabetic drugs to warn of the risks
    of heart failure.

### COMPLETE SUMMARY CONTENT

 \*\* REGULATORY ALERT \*\*\
 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 CONTRAINDICATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

Type 2 diabetes mellitus

#### GUIDELINE CATEGORY

Diagnosis\
Management\
Treatment

#### CLINICAL SPECIALTY

Endocrinology\
Family Practice\
Internal Medicine

#### INTENDED USERS

Advanced Practice Nurses\
Physician Assistants\
Physicians

#### GUIDELINE OBJECTIVE(S)

To support clinical practice and influence clinical behavior to improve
outcomes and assure quality of care according to accepted standards for
the pharmacological management of type 2 diabetes

#### TARGET POPULATION

Non-pregnant adults with type 2 diabetes mellitus

#### INTERVENTIONS AND PRACTICES CONSIDERED

1.  Diagnosis

    -   Casual plasma glucose

    -   Fasting plasma glucose

    -   Oral glucose tolerance test

2.  Treatment

    -   Glycemic control goals

    -   Initial treatment

        -   Mild presentation

        -   Moderate presentation

        -   Severe presentation

    -   Oral antihyperglycemic therapy:

        -   Metformin

        -   Thiazolidinediones

        -   Insulin secretagogue

        -   Alpha--glucosidase inhibitor

        -   Combination therapy

    -   Insulin

        -   Rapid-acting

        -   Short-acting

        -   Intermediate-acting

        -   Long-acting

        -   Pre-meal insulin mixture

    -   Exenatide

#### MAJOR OUTCOMES CONSIDERED

Glycemic control: fasting plasma glucose, 2-hour postprandial glucose,
and bedtime glucose levels, percent hemoglobin

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

Review of all new papers on selected topics in PubMed, MEDLINE, OUID,
Cochrane databases

#### NUMBER OF SOURCE DOCUMENTS

Not stated

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Weighting According to a Rating Scheme (Scheme Given)

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

  -----------------------------------------------------------------------
  **Grade of             **Clarity of        **Quality of Supporting
  Recommendation**       Risk/Benefit**      Evidence**
  ---------------------- ------------------- ----------------------------
  **1A**\                Benefits clearly    Consistent evidence from
  \                      outweigh risk and   well performed randomized,
  Strong recommendation\ vice versa.         controlled trials or
  High quality of                            overwhelming evidence of
  evidence                                   some other form. Further
                                             research is unlikely to
                                             change our confidence in the
                                             estimate of benefit and
                                             risk.

  **1B**\                Benefits clearly    Evidence from randomized,
  \                      outweigh risk and   controlled trials with
  Strong recommendation\ burdens, or vice    important limitations
  Moderate quality of    versa.              (inconsistent results,
  evidence                                   methodological flaws,
                                             indirect or imprecise), or
                                             very strong evidence of some
                                             other research design.
                                             Further research is likely
                                             to have an impact on our
                                             confidence in the estimate
                                             of the benefit and risk and
                                             may change the estimate.

  **1C**\                Benefits outweigh   Evidence from observational
  \                      risk and burdens,   studies, unsystematic
  Strong recommendation\ or vice versa.      clinical experience, or from
  Low quality of                             randomized controlled trials
  evidence                                   with serious flaws. Any
                                             estimate of effect is
                                             uncertain.

  **2A**\                Benefits closely    Consistent evidence from
  \                      balanced with risks well performed randomized,
  Weak recommendation\   and burdens.        controlled trials or
  High quality of                            overwhelming evidence of
  evidence                                   some other form. Further
                                             research is unlikely to
                                             change our confidence in the
                                             estimate of benefit and
                                             risk.

  **2B**\                Benefits closely    Evidence from randomized,
  \                      balanced with risks controlled trials with
  Weak recommendation\   and burdens; some   important limitations
  Moderate quality of    uncertainty in the  (inconsistent results,
  evidence               estimates of        methodological flaws,
                         benefits, risks,    indirect or imprecise), or
                         and burdens.        very strong evidence of some
                                             other research design.
                                             Further research is unlikely
                                             to have an impact on our
                                             confidence in the estimate
                                             of the benefit and risk and
                                             may change the estimate.

  **2C**\                Uncertainty in the  Evidence from observational
  \                      estimates of        studies, unsystematic
  Weak recommendation\   benefits, risks,    clinical experience, or from
  Low quality of         and burdens;        randomized controlled trials
  evidence               benefits may be     with serious flaws. Any
                         closely balanced    estimate of effect is
                         with risks and      uncertain.
                         burdens.            
  -----------------------------------------------------------------------

#### METHODS USED TO ANALYZE THE EVIDENCE

Review

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

Not stated

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

Not stated

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

  -----------------------------------------------------------------------
  **Grade of             **Clarity of        **Quality of Supporting
  Recommendation**       Risk/Benefit**      Evidence**
  ---------------------- ------------------- ----------------------------
  **1A**\                Benefits clearly    Consistent evidence from
  \                      outweigh risk and   well performed randomized,
  Strong recommendation\ vice versa.         controlled trials or
  High quality of                            overwhelming evidence of
  evidence                                   some other form. Further
                                             research is unlikely to
                                             change our confidence in the
                                             estimate of benefit and
                                             risk.

  **1B**\                Benefits clearly    Evidence from randomized,
  \                      outweigh risk and   controlled trials with
  Strong recommendation\ burdens, or vice    important limitations
  Moderate quality of    versa.              (inconsistent results,
  evidence                                   methodological flaws,
                                             indirect or imprecise), or
                                             very strong evidence of some
                                             other research design.
                                             Further research is likely
                                             to have an impact on our
                                             confidence in the estimate
                                             of the benefit and risk and
                                             may change the estimate.

  **1C**\                Benefits outweigh   Evidence from observational
  \                      risk and burdens,   studies, unsystematic
  Strong recommendation\ or vice versa.      clinical experience, or from
  Low quality of                             randomized controlled trials
  evidence                                   with serious flaws. Any
                                             estimate of effect is
                                             uncertain.

  **2A**\                Benefits closely    Consistent evidence from
  \                      balanced with risks well performed randomized,
  Weak recommendation\   and burdens.        controlled trials or
  High quality of                            overwhelming evidence of
  evidence                                   some other form. Further
                                             research is unlikely to
                                             change our confidence in the
                                             estimate of benefit and
                                             risk.

  **2B**\                Benefits closely    Evidence from randomized,
  \                      balanced with risks controlled trials with
  Weak recommendation\   and burdens; some   important limitations
  Moderate quality of    uncertainty in the  (inconsistent results,
  evidence               estimates of        methodological flaws,
                         benefits, risks,    indirect or imprecise), or
                         and burdens.        very strong evidence of some
                                             other research design.
                                             Further research is unlikely
                                             to have an impact on our
                                             confidence in the estimate
                                             of the benefit and risk and
                                             may change the estimate.

  **2C**\                Uncertainty in the  Evidence from observational
  \                      estimates of        studies, unsystematic
  Weak recommendation\   benefits, risks,    clinical experience, or from
  Low quality of         and burdens;        randomized controlled trials
  evidence               benefits may be     with serious flaws. Any
                         closely balanced    estimate of effect is
                         with risks and      uncertain.
                         burdens.            
  -----------------------------------------------------------------------

#### COST ANALYSIS

A formal cost analysis was not performed and published cost analyses
were not reviewed.

#### METHOD OF GUIDELINE VALIDATION

Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

The guideline was approved by the Joslin Clinical Oversight Committee on
1/12/07.

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

Definitions of the recommendation and evidence level grades (1A to 2C)
are provided at the end of the \"Major Recommendations\" field.

+-----------------------------------------------------------------------+
| **Diabetes Mellitus -- Diagnostic Criteria (Non-Pregnant Adult)**     |
+=======================================================================+
| -   Casual plasma glucose [\>]{.underline} 200 mg/dl and symptoms of  |
|     diabetes (polyuria, polydipsia, ketoacidosis, or unexplained      |
|     weight loss) **OR**                                               |
|                                                                       |
| -   Fasting plasma glucose (FPG) [\>]{.underline} 126 mg/dl **OR**    |
|                                                                       |
| -   Results of a 2-hour 75-g Oral Glucose Tolerance Test (OGTT)       |
|     [\>]{.underline} 200 mg/dl                                        |
+-----------------------------------------------------------------------+

 

  ------------------------------------------------------------------------------
  **Goals of Glycemic Control for People with                         
  Diabetes^1^**                                                       
  ------------------------------------------------------ ------------ ----------
  **Biochemical Index**                                  **Normal**   **Goal**

  Average Fasting Plasma Glucose or Preprandial Glucose  \< 100       90 -- 130
  (mg/dl)                                                             

  Average Postprandial 2 hours (mg/dl)                   \< 140       \< 160

  Average Bedtime Glucose (mg/dl)                        \< 120       110 -- 150

  A1C (%) - sustained                                    \< 6%        \< 7%^2^
  ------------------------------------------------------------------------------

^1^Laboratory methods measure plasma glucose. Most glucose monitors
approved for home use calibrate whole blood glucose readings to plasma
values. Plasma glucose values are 10-15% higher than whole blood glucose
values. It is important for people with diabetes to know whether their
meters and strips record whole blood or plasma results.

^2^The true goal of care is to bring A1C as close to normal as safely
possible. \[**1C**\] A goal of \< 7% is chosen as a practical level for
most patients using medications that may cause hypoglycemia to avoid the
risk of that complication. Achieving normal blood glucose is recommended
if it can be done practically and safely. **\[1B\]**

The guideline recommendations are presented in a series of algorithms on
the following topics:

-   Initial Treatment Strategy

-   Considerations for Selecting Initial Oral Antihyperglycemic Therapy

Refer to the original guideline document for more information.

**Definitions**:

  -----------------------------------------------------------------------
  **Grade of             **Clarity of        **Quality of Supporting
  Recommendation**       Risk/Benefit**      Evidence**
  ---------------------- ------------------- ----------------------------
  **1A**\                Benefits clearly    Consistent evidence from
  \                      outweigh risk and   well performed randomized,
  Strong recommendation\ vice versa.         controlled trials or
  High quality of                            overwhelming evidence of
  evidence                                   some other form. Further
                                             research is unlikely to
                                             change our confidence in the
                                             estimate of benefit and
                                             risk.

  **1B**\                Benefits clearly    Evidence from randomized,
  \                      outweigh risk and   controlled trials with
  Strong recommendation\ burdens, or vice    important limitations
  Moderate quality of    versa.              (inconsistent results,
  evidence                                   methodological flaws,
                                             indirect or imprecise), or
                                             very strong evidence of some
                                             other research design.
                                             Further research is likely
                                             to have an impact on our
                                             confidence in the estimate
                                             of the benefit and risk and
                                             may change the estimate.

  **1C**\                Benefits outweigh   Evidence from observational
  \                      risk and burdens,   studies, unsystematic
  Strong recommendation\ or vice versa.      clinical experience, or from
  Low quality of                             randomized controlled trials
  evidence                                   with serious flaws. Any
                                             estimate of effect is
                                             uncertain.

  **2A**\                Benefits closely    Consistent evidence from
  \                      balanced with risks well performed randomized,
  Weak recommendation\   and burdens.        controlled trials or
  High quality of                            overwhelming evidence of
  evidence                                   some other form. Further
                                             research is unlikely to
                                             change our confidence in the
                                             estimate of benefit and
                                             risk.

  **2B**\                Benefits closely    Evidence from randomized,
  \                      balanced with risks controlled trials with
  Weak recommendation\   and burdens; some   important limitations
  Moderate quality of    uncertainty in the  (inconsistent results,
  evidence               estimates of        methodological flaws,
                         benefits, risks,    indirect or imprecise), or
                         and burdens.        very strong evidence of some
                                             other research design.
                                             Further research is unlikely
                                             to have an impact on our
                                             confidence in the estimate
                                             of the benefit and risk and
                                             may change the estimate.

  **2C**\                Uncertainty in the  Evidence from observational
  \                      estimates of        studies, unsystematic
  Weak recommendation\   benefits, risks,    clinical experience, or from
  Low quality of         and burdens;        randomized controlled trials
  evidence               benefits may be     with serious flaws. Any
                         closely balanced    estimate of effect is
                         with risks and      uncertain.
                         burdens.            
  -----------------------------------------------------------------------

#### CLINICAL ALGORITHM(S)

The original guideline document contains clinical algorithms for:

-   Initial Treatment Strategy

-   Considerations for Selecting Initial Oral Antihyperglycemic Therapy

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The type of supporting evidence is identified and graded for each
recommendation.

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

Appropriate pharmacological management of type 2 diabetes

#### POTENTIAL HARMS

-   Hypoglycemia

-   Thiazolidinediones can be used in renal impairment but may increase
    fluid retention

### CONTRAINDICATIONS

#### CONTRAINDICATIONS

-   Metformin is contraindicated in the following conditions:

    -   Creatinine [\>]{.underline} 1.4 (women)

    -   Creatinine [\>]{.underline} 1.5 (men)

    -   Intravenous (IV) contrast

    -   Congestive heart failure (CHF)

    -   Dehydration

    -   Alcohol excess

    -   [\>]{.underline} 80 years of age (unless creatinine clearance is
        normal)

-   Thiazolidinediones are contraindicated in the following conditions:

    -   Class III or IV CHF

    -   Liver function tests \> 2.5 times upper limit of normal

-   Insulin secretagogues (sulfonylurea or short-acting secretagogue)
    are contraindicated in the following conditions:

    -   Sulfonylureas in severe liver or renal disease

-   Alpha-glucosidase inhibitors are contraindicated in the following
    conditions:

    -   Chronic intestinal disorders

    -   Acarbose in cirrhosis

    -   Acarbose and miglitol in renal impairment (creatinine \> 2.0)

-   Exenatide is contraindicated in gastroparesis requiring treatment
    with metoclopramide

-   Inhaled insulin is contraindicated in smokers, recent smokers and
    patients with underlying lung disease

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

This Clinical Guideline is not intended to serve as a mandatory
standard, but rather provides a set of recommendations for patient care
management. These recommendations are not a substitute for sound and
reasonable clinical judgment or decision-making and do not exclude other
options. Clinical care must be individualized to the specific needs of
each patient and interventions must be tailored accordingly. The
guideline has been created to address initial presentation and treatment
strategies in the adult non-pregnant patient population.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

An implementation strategy was not provided.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Living with Illness

#### IOM DOMAIN

Effectiveness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

Joslin Diabetes Center. Clinical guideline for pharmacological
management of type 2 diabetes. Boston (MA): Joslin Diabetes Center; 2007
Jan 12. 9 p. \[91 references\]

#### ADAPTATION

Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

2007 Jan 12

#### GUIDELINE DEVELOPER(S)

Joslin Diabetes Center - Hospital/Medical Center

#### SOURCE(S) OF FUNDING

Joslin Diabetes Center

#### GUIDELINE COMMITTEE

Joslin Clinical Oversight Committee

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

*Committee Members*: James Rosenzweig, MD (*Chairperson*); Richard
Beaser, MD; Elizabeth Blair, MS, CS-ANP, CDE; Patty Bonsignore, MS, RN,
CDE; Amy Campbell, MS, RD, CDE; Cathy Carver, ANP, CDE; Jerry
Cavallerano, OD, PhD; Om Ganda, MD; John W. Hare, MD; Lori Laffel, MD,
MPH; Melinda Maryniuk, MEd, RD; William Petit, MD; Kristi Silver, MD;
Susan Sjostrom, JD; Kenneth Snow, MD; Robert Stanton, MD; William
Sullivan, MD; Howard Wolpert, MD; Martin J. Abrahamson, MD (*ex
officio*)

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

Not stated

#### GUIDELINE STATUS

This is the current release of the guideline.

This guideline will be reviewed periodically and modified to reflect
changes in clinical practice and available pharmacological information.

#### GUIDELINE AVAILABILITY

Electronic copies: Available in Portable Document Format (PDF) from the
[Joslin Diabetes
Center](http://www.joslin.org/Files/Pharm_Guideline_Graded.pdf).

Print copies: Available from the Joslin Diabetes Center, One Joslin
Place, Boston, MA 02215

#### AVAILABILITY OF COMPANION DOCUMENTS

None available

#### PATIENT RESOURCES

None available

#### NGC STATUS

This NGC summary was completed by ECRI Institute on April 19, 2007. The
information was verified by the guideline developer on May 10, 2007.
This summary was updated by ECRI Institute on September 5, 2007
following the U.S. Food and Drug Administration advisory on the
Thiazolidinedione class of antidiabetic drugs. This summary was updated
by ECRI Institute on November 6, 2007, following the U.S. Food and Drug
Administration advisory on Byetta (exenatide). This summary was updated
by ECRI Institute on November 28, 2007 following the U.S. Food and Drug
Administration advisory on the Avandia (rosiglitazone maleate) Tablets.
This summary was updated by ECRI Institute on March 10, 2008 following
the U.S. Food and Drug Administration advisory on Avandia (rosiglitazone
maleate). This summary was updated by ECRI Institute on April 21, 2008
following the U.S. Food and Drug Administration advisory on Exubera
(insulin human rDNA origin) Inhalation Powder.

#### COPYRIGHT STATEMENT

This NGC summary is based on the original guideline, which is subject to
the guideline developer\'s copyright restrictions.

### DISCLAIMER

#### NGC DISCLAIMER

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© 1998-2008 National Guideline Clearinghouse

Date Modified: 11/3/2008