Diabetes Treatment in Rural Guatemala
Conditions: Diabetes
Sponsor: University of Wisconsin, Madison

Diabetes Treatment in Rural Guatemala 
 
Jim Svenson 
 
1 
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DIABETES TREATMENT IN RURAL GUATEMALA 
 
 
A single group, pre-and post-test feasibility/pilot study of a smartphone application to assist community health 
workers in improving glycemic control in patients with type 2 diabetes in highland Guatemala.  
 
 
Principal Investigator: Jim Svenson 
 
 
 
 
This document is confidential. 
No part of it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the Sponsor or Principal Investigator. 
 
 
 
 
 
 
PROTOCOL VERSION and AMENDMENTS 
 
Protocol 
Version 
Date 
Change 
Initiated 
(Initials) 
Brief 
description 
of 
protocol 
modification/actions 
requested, if any 
Template 
V6 
9/6/16 
TNK 
Input from IRB, OCT, MARCH, IND/IDE services, PIs 
1.0 
11/13/17 
SMD 
Initial submission 
1.1 
12/20/17 
SMD 
Updates on storage of study data (section 9.1) 
1.2 
12/21/17 
SMD 
Change to urgency of referral for vision problems, removed 
Alejandro Chavez from Key Personnel section  
1.3 
2/20/18 
SMD 
Changed hosting platform from Ona to CommCare 
 
 
 
 
 
 
 
 
 
 
 
 

Diabetes Treatment in Rural Guatemala 
 
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Funding Sponsor: 
University of Wisconsin Global Health Institute 
4270B Health Sciences Learning Center, 750 Highland Avenue,  
(608) 262-3862 
Study Product: 
Smartphone application for assisting community health workers 
with diabetes care in low resource areas  
Protocol Number: 
2017-0596 (IRB application number) 
IND/IDE Number: 
Not applicable  
 
    Participating sites:  
         San Lucas Mission, San Lucas Tolimán, Guatemala 
 
 
 
 

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List of Abbreviations 
 
ACS 
Acute coronary syndrome 
AE 
Adverse event 
ANOV
A 
Analysis of covariance 
ASCVD 
Atherosclerotic cardiovascular disease 
BP 
Blood pressure 
CAD 
Coronary artery disease 
CFR 
Code of Federal regulations 
CHW 
Community health worker 
CKD 
Chronic kidney disease 
CLIA 
Clinical Laboratory Improvement Amendments 
COPD 
Chronic obstructive pulmonary disease 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CVD 
Cerebrovascular disease 
DBP 
Diastolic blood pressure 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data Safety Monitoring Board  
eCRF 
Electronic Case Report Forms 
FBG 
Fasting blood glucose 
FDA 
Food and Drug Administration 
FFR 
Federal Financial Report 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
GWAS 
Genome-Wide Association Studies 
HIPAA 
Health Insurance Portability and Accountability Act 
IB 
Investigator’s Brochure 
ICH E6 
International Conference on Harmonisation Guidance for Industry, Good Clinical Practice: 
Consolidated Guidance 
ICMJE 
International Committee of Medical Journal Editors  
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IRB 
Investigational Review Board 
ISO 
International Organization for Standardization 
LMICs 
Low- and middle-income countries 
MOP 
Manual of Procedures 
MSDS 
Material Safety Data Sheet 
NIH IC 
NIH Institute & Center 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
POC 
Point-of-care 
PPBG 
Postprandial blood glucose 
QA 
Quality Assurance 
QC 
Quality Control 
SBP 
Systolic blood pressure 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 

Diabetes Treatment in Rural Guatemala 
 
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SLM 
San Lucas Mission 
SLMH 
San Lucas Mission Hospital 
SMC 
Safety Monitoring Committee 
 
 
 

Diabetes Treatment in Rural Guatemala 
 
Jim Svenson 
 
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Study Summary 
 
Title 
Diabetes Treatment Algorithm for Minimally Trained Providers in Rural 
Guatemala 
Short Title and Precis 
Diabetes Treatment in Rural Guatemala. Implementation of a diabetes 
treatment program led by community health workers (CHWs) using a 
smartphone application to provide protocol-driven care. 
Protocol Number 
2017-0596 
ClinicalTrials.gov 
number 
NA 
Phase 
NA, implementation and feasibility study 
Methodology 
Single group, pre-and post-test feasibility/pilot study. 
Study Duration 
The expected duration of subject participation from enrollment to study 
completion (including follow up) is 12 months  
Study Center(s) 
Multi-center. Site will be the rural communities surrounding San Lucas 
Tolimán, Guatemala 
Objectives 
1. Implement a CHW-led diabetes program to improve diabetes care in 
the rural communities surrounding San Lucas Tolimán, Guatemala 
2. Assess the efficacy of CHWs equipped with a smartphone application 
on improving glycemic control in this setting 
Number of Subjects 
100 to 150 
Diagnosis  
Type 2 diabetes mellitus 
Main Inclusion Criteria 
Adults 18 years and older with previously-diagnosed type 2 diabetes 
Main Exclusion 
Criteria 
Pregnancy, insulin dependency, type 1 diabetes 
Study Product, Dose, 
Route, Regimen 
Study uses a smartphone application to guide CHWs through treatment 
protocols, which was developed for the purposes of this study. Drugs used in 
the program are metformin, glibenclamide and aspirin.   
FDA status of product 
Drugs used are FDA approved 
Statistical 
Methodology 
Continuous variables will be assessed with paired t-tests. Categorical 
variables will be analyzed using the McNemar test for binary matched-pairs 
data.  
 
 
 

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Diabetes Treatment in Rural Guatemala 
 
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Contents 
Study Summary 
5 
1 
Key Roles 
11 
2 
Background and Introduction 
11 
2.1 
Background and Rationale 
11 
2.2 
Hypothesis 
14 
2.3 
Study Agent 
14 
2.4 
Summary of Relevant Preclinical Data 
15 
2.5 
Summary of Clinical Data 
15 
2.6 
Dose Rationale 
15 
2.7 
Potential Risk and Benefits to Subjects 
16 
2.7.1 
Known Potential Risks 
16 
2.7.2 
Protection Against Risks 
17 
2.7.3 
Potential Benefits to the Subjects 
18 
3 
Study Objectives and Purpose 
18 
4 
Study Design and Endpoints 
18 
4.1 
General Design 
18 
4.1.1 
Primary Study Endpoints 
19 
4.1.2 
Secondary Study Endpoints 
19 
4.1.3 
Primary Safety Endpoints 
19 
5 
Study Subjects – Enrollment and Withdrawal 
19 
5.1 
Subject Population 
19 
5.2 
Inclusion Criteria 
20 
5.3 
Exclusion Criteria 
20 
5.4 
Subject Screening for Recruitment 
20 
5.4.1 
Subject Identification 
20 
5.4.2 
Recruitment and Retention Strategies 
20 
5.5 
Vulnerable Populations 
20 
5.5.1  
Subject Capacity 
21 
5.5.2  
Subject/Representative Comprehension 
21 
5.6 
Informed Consent 
21 
5.6.1 
Process of Consent 
21 
5.6.2 
Consent Form (see templates for UW-Madison) 
21 
5.6.3 
HIPAA 
21 
5.6.4 
Revoking Consent 
22 
5.6.5  
Costs to the Subject 
22 
5.6.6 
Payment for Participation 
22 

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5.7 
Early Withdrawal of Subjects 
22 
5.7.1 
Premature termination of study 
22 
5.7.2 
When and How to Withdraw Subjects 
22 
5.7.3    Data Collection and Follow-up for Withdrawn Subjects 
23 
6 
Study Agent 
23 
6.1 
Description and Formulation 
23 
6.2 
Packaging 
23 
6.3 
Preparation, Administration and Storage of Study Drug 
23 
6.4 
Route of Administration 
23 
6.5 
Starting Dose and Dose Escalation Schedule 
23 
6.6 
Dose Adjustments/Modifications/Delays 
24 
6.7 
Prior and Concomitant Therapy/ Standard of Care 
24 
6.8 
Randomization and Blinding of Study Drug 
24 
6.9 
Receiving, Storage, Dispensing and Return or Disposal of Study Agent 
24 
6.9.1 
Receipt of Drug Supplies 
24 
6.9.2 
Storage 
25 
6.9.3 
Dispensing 
25 
6.9.4 
Return or Disposal 
25 
7 
Study Procedures 
25 
7.1 
LABS 
25 
7.2 
Established Standard of Care: 
26 
7.3 
Study Visits 
26 
7.4.1 
Screening/Baseline: 
26 
7.4.2 
Follow up: 
28 
7.4.3 
Unscheduled: 
29 
8 
Study Analysis 
29 
8.1 
Sample Size Determination 
29 
8.2 
Statistical Methods 
30 
8.3 
Subject Population(s) for Analysis 
30 
8.4 
Planned Interim Analysis: 
30 
9 
Data Collection, Handling and Record Keeping 
31 
9.1 
Data Confidentiality 
31 
9.1.1 
Confidentiality of Subject Records 
31 
9.2 
Data Capture 
32 
9.2.1 
Source Documents 
32 
9.2.2 
Case Report Forms 
32 
9.2.2.1 
Missing Data 
32 
9.2.3 
Data Collection Tools 
32 

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9.3 
Data Management 
32 
9.4 
Data Monitoring 
32 
9.5 
Records Retention 
32 
9.6 
Specimen Banking 
32 
10 
Assessment of Safety 
32 
10.1 
Specifications of Safety Parameters 
32 
10.1.1 
Definition of Adverse Events (AE) 
33 
10.1.2 
Definition of Serious Adverse Events (SAE) 
33 
10.1.3 
Definition of Unanticipated Problems (UP) 
33 
10.2 
Classification of an Adverse Event 
33 
10.2.1 
Severity of Event 
33 
10.2.3 
Expectedness 
34 
10.3 
Time period and frequency for event assessment and follow-up 
34 
10.4 
Reporting procedures 
35 
10.4.1 
Adverse Event Reporting 
35 
10.4.2 
Serious adverse event reporting 
35 
10.4.3 
Unanticipated problem reporting 
36 
10.4.4 
Events of special interest 
36 
10.4.5 
Reporting of pregnancy 
36 
10.5 
Study Halting Rules 
37 
10.6 
Safety Oversight 
37 
10.7 
Unblinding Procedure 
37 
11 
Study Monitoring, Auditing, and Inspecting 
37 
11.1 
Medical Monitoring 
37 
11.1.1 
Study Monitoring Plan 
37 
11.2 
Protocol Deviations 
38 
11.2.1 Internal Data and Safety Monitoring Board 
38 
11.3 Auditing and Inspecting 
38 
11.4 Subject Compliance Monitoring 
38 
12 Ethical Considerations 
38 
13 Study Finances 
39 
13.1 Funding Source 
39 
13.2 Conflict of Interest 
39 
14 Publication Plan 
39 
15 References 
39 
Appendices 
44 
Appendix 1 - Screening Questions, Demographic Information, and Past Medical History 
44 
Appendix 2 - Aspirin for Secondary Prevention of ASCVD 
45 

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Appendix 3 - Medication History, Side Effects, and Adherence 
46 
Appendix 4 - Hypoglycemia Protocol 
48 
Appendix 5 - Hyperglycemia Protocols 
50 
Appendix 6 - Complications of Diabetes Protocols 
51 
Appendix 7 - Referrals Protocols 
52 
Appendix 8 - Enrollment Medication Dosing Recommendations 
53 
Appendix 9 - Medication Instructions 
62 
Appendix 10 - Monthly Medication Dosing Recommendations 
63 
Appendix 11 - Month 3 Dosing Recommendations 
75 
Appendix 12 - Blood Pressure Protocol 
84 
 
 
 
 

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1 Key Roles 
Following is a list of all personnel in key roles: 
 
        
Jim Svenson, MD, Primary Investigator 
University of Wisconsin-Madison School of Medicine and Public Health 
800 University Bay Rd, Rm 349, Madison, WI 53705 
608-215-3216 
jes@medicine.wisc.edu 
  
Sean Duffy, MD, Co-investigator 
University of Wisconsin-Madison School of Medicine and Public Health 
1102 S Park St, Madison, WI 53715 
608-354-7930 
sean.duffy@fammed.wisc.edu 
  
Rafael Tun, MD, Site investigator 
San Lucas Mission 
La Parroquia, San Lucas Tolimán, Sololá, Guatemala 
+502-7722-0899 
dr.rafael.tun@gmail.com 
 
Mark Kelly, MD Candidate 2019, Research Assistant 
University of Wisconsin-Madison School of Medicine and Public Health 
750 Highland Ave, Madison, WI 53726 
608-338-8949 
mmkelly2@wisc.edu 
 
Kevin Wyne, MPAS, MSc, PA-C, Co-investigator 
University of Wisconsin-Madison School of Medicine and Public Health 
750 Highland Avenue, Room 1278, Madison, WI 53705 
608-263-5620 
kwyne@wisc.edu 
 
2 Background and Introduction 
 
 
2.1 Background and Rationale 
 
The burden of chronic adult diseases is surging worldwide, particularly type 2 diabetes, the prevalence of 
which is expected to double by 2030. The diabetes epidemic will primarily impact developing countries, with 
80% of adult cases occurring in low- and middle-income countries (LMICs) 1–4. Because many LMICs 
currently face a shortage of health professionals, the increasing burden of noncommunicable diseases, like 
type 2 diabetes, will tax already strained health systems5–8. Furthermore, because many LMIC health care 
systems were developed to target acute illnesses and communicable disease, they are ill-prepared to treat 
and manage chronic adult disease9,10. The divergence between the growing burden of chronic disease and 
the development of the health systems necessary to treat these diseases indicate the potential for a grave 
health, economic, and human crisis in the following decades. The WHO has consequently demanded that 
physicians designs systems providing “Innovative Care for Chronic Conditions” to meet this challenge4. 
 

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However, existing tools may provide a foundation for solutions to this growing crisis. Community Health 
Workers (CHWs, as known as health promoters) have become central to global health strategies since the 
Alma Ata Declaration of 1978, particularly in regions with physician shortages11. In recent years, CHWs have 
had notable success in targeting childhood disease, particularly malnutrition and diarrhea, and offer a growing 
variety of primary care services12–15. The success of these programs in providing consistent, sustainable care 
at the local level implies that longitudinal treatment for chronic adult diseases could be provided through 
parallel structures. While the treatment of chronic disease has become increasingly complex, the proliferation 
of smartphone and tablets across the globe have raised hopes that mobile health technology (mHealth) 
platforms can provide CHWs with algorithmic guidance on assessing and treating a broader set of 
diseases8,16. The potential use of mHealth is a burgeoning field of global health research17. The combination 
of CHWs and mHealth guidance may provide a solution to the rise of chronic disease in regions with 
physician shortages and weak health systems. 
 
While many mHealth applications have been developed for Diabetes (over 1,000 are commercially available), 
only a small percentage (7.6%) are targeted to providers – and even fewer to providers in LMICs18,19. Instead, 
these tools most commonly serve as tools for patient self-management, patient education, and medication 
adherence. A handful of programs have utilized smartphone technology to connect remote patients to health 
care workers in LMICs as well as to provide clinical guidance to providers, but such programs have been 
minimal and publications have been process oriented20,21. In addition to improving diabetes care in our target 
population, our project also seeks to add to the evidence for this approach by designing an application-based 
algorithm that can assist CHWs in providing long-term diabetes care, titrating first- and second-line oral 
diabetes medications, and identifying dangerous diabetes complications in a setting of a lower middle-income 
country with a low physician density.  
 
To test this delivery approach, we focused on developing a diabetes treatment program in San Lucas 
Tolimán, Guatemala. This program seeks to provide treatment to diabetics living in the group of 19 rural 
villages with a combined population of 17,000, which surround San Lucas. San Lucas is an ideal community 
for studying these topics because it is facing a heavy burden of untreated Type II Diabetes, has medical 
personnel with mHealth experience, and has a well-developed CHW program. This CHW program is 
sponsored by the San Lucas Mission (SLM), an NGO providing health services in the area and a University of 
Wisconsin and Stanford University partner organization. Local health workers describe the increase in Type II 
Diabetes as an epidemic and there are few systems in place to provide community members with diabetes 
screening or effective and consistent treatment. Startling regional data on Type II Diabetes supports this 
concern: in Guatemala, the prevalence of diabetes has been estimated at 9.1-9.4%, with over 40% of cases 
undiagnosed22–24. The prevalence of diabetes has doubled over the past 30 years25. Fortunately, San Lucas 
has already developed a strong CHW program, including a tablet-based mHealth application that targets early 
childhood malnutrition, through a collaboration between the San Lucas Mission and Stanford School of 
Medicine. This application has enhanced the successful malnutrition program, allowing CHWs to more easily 
identify and manage malnutrition and decreasing training requirements for CHWs26. Utilizing the existence of 
the CHW program infrastructure and the established mHealth platform, our project seeks to develop and 
implement a CHW-led diabetes treatment program in San Lucas that is assisted by a smartphone application.  
 
In order to inform the development of the smartphone application and program protocols, we conducted a 
community needs assessment during the summer of 2016. Clinical data was used to provide a baseline 
estimate of diabetes prevalence and distribution in the communities as well as demographic risk factors. 
Interviews were conducted with local physicians, CHWs, and managers of the CHW system to understand 
current methods of diabetes treatment and define the limitations of these systems. Out of the 119 patients 
currently diagnosed with diabetes in the rural communities, 31 were interviewed to illuminate how the disease 
is currently diagnosed and treated, the effect the disease has on patient lifestyles, and patients’ desired 
attributes for a diabetes treatment program. Finally, we visited local diabetes clinics to determine the current 
state of diabetes treatment, the availability of medications and resources, and the level of care provided to 
patients. 
 
Key findings of the community needs assessment were as follows: 

Diabetes Treatment in Rural Guatemala 
 
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1. Patients with diabetes in the rural communities have poor access to quality diabetes care. Only 
58% of patients are taking medication on a regular basis and only 13% have achieved good 
glycemic control 
2. Outreach clinics run by CHWs are disorganized, undersupplied, sporadic, and ineffective 
3. CHWs lack the experience and training to effectively titrate oral diabetes medications, assess for 
possible complications, and provide health education for patients 
4. Patients lack basic diabetes knowledge, particularly regarding self-management 
 
Utilizing the knowledge gained with this needs assessment, established treatment guidelines for diabetes, 
and the expertise of SLM medical director Dr. Rafael Tun and the coordinators the SLM CHW program, we 
developed protocols for the diabetes program, including a smartphone application to allow for algorithmic 
management. This process was iterative and collaborative and involved our local partners at every step.  
 
In February and March, we trained a group of 10 CHWs, including 5 CHW coordinators (who have more 
clinical experience and take on a supervisory and training role for less-experienced CHWs) in the basics of 
diabetes management, program protocols, and the use of the smartphone application we had developed. 
With close physician supervision, we then beta-tested the use of the application with a small group of 
patients. Based on this experience, we have further refined the application and program protocols. We now 
endeavor to implement this program on a wide scale in the San Lucas area to both improve access to care for 
patients with diabetes and to establish the efficacy, feasibility, and safety of CHW-led, smartphone 
application-guided diabetes treatment. 
 
CHW training, program protocols, and the algorithmic approaches facilitated by the smartphone application 
will be described in more detail in the relevant sections of this protocol and its appendices. An overview of 
study activities is as follows: 
 
● 
We will train additional CHWs in basic diabetes care, use of point-of-care (POC) testing technology, and 
use of the smartphone application that will guide their management of patients with diabetes. 
● 
CHWs will recruit patients with diabetes in the rural villages outside of San Lucas to participate in the 
program. 
● 
At the enrollment visit, CHWs will use the smartphone application to screen patients for appropriate 
inclusion in the program, establish glycemic targets, assess current glycemic control with hemoglobin A1c 
and blood glucose, measure height, weight, blood pressure, and waist circumference, assess for the 
presence of diabetes complications (diabetic ulcers, angina, diabetic eye disease), administer oral 
medications (metformin and/or glyburide, known locally by its alternate name glibenclamide) based on a 
medication dosing algorithm, and provide diabetes self-management education. 
● 
CHWs will meet with patients on a monthly basis to assess medication adherence and for adverse 
effects, glycemic control (with blood glucose), screen for diabetic complications, refill medications with 
titration as needed (if experiencing medication adverse effects or blood glucose is significantly above or 
below treatment goals), and provide further diabetes education. Again, these activities will be guided by 
the smartphone application. Every 3 months, the monthly visit will also include A1c measurement for a 
more definitive measurement of diabetes control and to allow for titration of medications. Patients who are 
identified as having complications or who are not meeting treatment goals despite maximal dosing of 
metformin and glibenclamide allowed by the algorithm will be referred to SLM medical director Dr. Rafael 
Tun for definitive management.  
● 
After all visits, including enrollment and monthly visits, Dr. Tun, in addition to the study investigators, will 
review data for all patients seen, including treatment recommendations made by the application and 
carried out by the CHWs, and make any changes to the treatment plan as needed based on his clinical 
judgement.  
● 
Mean hemoglobin A1c and proportion of patients meeting treatment goals (primary endpoints) will be 
assessed at 6 months and compared to baseline, in addition to a number of secondary endpoints and 
safety measures as described in the relevant sections of this protocol. If possible, patients will also be 
followed out to 12 months with reassessment of primary and secondary endpoints.  

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● 
SLM hopes to continue this rural diabetes treatment program indefinitely, with the results of this study 
informing a quality improvement process to ensure the provision of high quality care.  
 
A potentially controversial aspect of this program is that CHWs will be making metformin and glibenclamide dose 
adjustments based on an algorithmic protocol, with physician oversight occurring in a retrospective fashion. 
However, this approach has been used safely and effectively for chronic disease management in LMIC. For 
example, a validation study of the WHO CVD-Risk Management Package in India found that frontline health 
workers following a treatment algorithm for hypertension made the same decision as a physician with regarding to 
prescribing a thiazide diuretic 88-97% of the time27. Additionally, a diabetes treatment program in rural Guatemala 
working with indigenous patients, a population analogous to our target population, successfully utilized protocol-
based care carried out by nurses to safely improve glycemic control and other treatment parameters28.  
 
We believe that the novel aspect of our intervention, the use of a smartphone application to guide treatment 
decisions, improves on these protocol-driven approaches in several ways. The use of a mobile computer-based 
algorithm as opposed to a paper algorithm allows for greater complexity and the incorporation of additional factors 
relevant to patient safety, such as the patient’s current dose of medication, medication adherence, and medication 
side effects, in order to provide more specific recommendations. In this way, it decreases the cognitive burden 
placed on CHWs and the potential for human error. Rather than having to follow a complicated paper flowchart, 
CHWs will input information into the smartphone application, which will process the data and present the CHW 
with a concrete recommendation. Additionally, a computer-based system allows for easier review by the 
supervising physician and auditing and analysis of both program process measures and outcomes.  
 
While CHWs will be acting on recommendations from the smartphone application without direct physician 
supervision at that moment, they will in essence be acting on “standing orders” from the physician because the 
treatment algorithms were designed by physicians and approved by the SLM medical director. CHWs will also be 
able to obtain point-of-care treatment recommendations from the medical director via telephone if there are 
questions about application recommendations or if a situation arises that falls outside the scope of the protocols.  
2.2 Hypothesis 
 
We hypothesize that the implementation of a CHW-led diabetes program utilizing algorithmic guidance from a 
smartphone application in the rural communities surrounding San Lucas Tolimán will lead to an improvement 
in glycemic control among the diabetic patients enrolled in the program.  
2.3 Study Agent 
 
In this study, we will be using a smartphone application that we developed to guide CHWs through the clinical 
assessment of patients with diabetes including collection of demographic data and past medical history, 
assessment of medication history, adherence, and adverse effects, measurement of glycemic control, 
screening for complications, medication administration and titration, and patient counseling. The application 
uses the CommCare platform by Dimagi and will be run on password-protected and encrypted Android 
smartphones. This application is based on web forms, which allow for skip logic questions and algorithmic 
processing of data. The application can be used offline. When internet access is available, collected data is 
uploaded to a secure server. The specific protocols and algorithms programmed into this application are 
described in further detail in the relevant sections of this protocol and its appendices.  
 
We will use the following medications in our study (all FDA approved and being used for approved 
indications): 
 
● 
Metformin HCl regular-release tablets 850 mg29 
○ 
Description: Oral biguanide antidiabetic medication. First line medication for type 2 diabetes and 
used as monotherapy or in combination with other medications. Low risk of lactic acidosis 
Deleted: consists of Enketo
Deleted: utilize Excel-based programing to 
Deleted: These forms run in a smartphone browser 
and
Deleted: In our case, we are using password-protected 
Android smartphones with the Google Chrome mobile 
browser. 

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○ 
Pharmacology: Decreases hepatic glucose production and increases insulin sensitivity. Not 
metabolized hepatically. Excreted largely intact by the kidney. Elimination half-life 17.6 hours 
● 
Glibenclamide (glyburide) regular-release tablets 5 mg30 
○ 
Description: Oral 2nd generation sulfonylurea antidiabetic medication. 2nd line treatment for type 
2 diabetes 
○ 
Pharmacology: Stimulates insulin release from pancreatic islet cells. May also cause reduction in 
hepatic glucose production and increase insulin sensitivity with prolonged use. Metabolized 
completely by the liver to 2 weakly active metabolites. Excreted in urine and feces. Terminal 
elimination half-life is 10 hours and duration of action is 18-24 hours 
● 
Aspirin (acetylsalicylic acid) 81 mg tablet31 
○ 
Description: Oral salicylate with analgesic, anti-inflammatory, and antithrombotic effects. Used for 
the treatment of ACS, ischemic stroke and primary and secondary prevention of ASCVD. 
○ 
Pharmacology: Inhibits cyclooxygenase (COX) and thus decreases thromboxane A2, leading to 
decreased vasoconstriction and platelet inhibition. Metabolized rapidly by the liver to salicylic 
acid, which has a half-life of 3-10 hours depending on dose. Excreted in the urine. 
 
FDA drug inserts for these medications have been uploaded to the ARROW application 
2.4 Summary of Relevant Preclinical Data 
 
No available research 
2.5 Summary of Clinical Data 
 
No available research 
2.6 Dose Rationale  
 
The standard doses for metformin and glibenclamide used in our program are as follows: 
 
● 
Metformin: 850 mg, 1500 mg, or 2550 mg per day (850 mg dosed once, twice, or three times 
daily, respectively) 
● 
Glibenclamide: 2.5 mg, 5 mg, or 10 mg one time daily 
 
In accordance with diabetes treatment guidelines32–34, metformin is the first line medication for all patients in 
the program and is continued in all patients as long as it is tolerated and there are no contraindications. The 
standard starting dose of metformin in our protocol is 1700 mg (850 mg twice daily) as 1500 - 2000 mg is 
thought to be the usual effective dose range35,36.  
 
Also in accordance with ADA and AACE guidelines, patients with initial or repeat A1c ≥9% are placed on dual 
therapy with metformin and glibenclamide. For patients who are initially started on metformin alone and 
whose A1c is <9%, glibenclamide is added if they are not meeting glycemic targets despite maximum daily 
dose of metformin (2550 mg). Though the maximum dose of glibenclamide is 20 mg, most of the 
hypoglycemic effect of glibenclamide is thought to come at the initial 2.5 mg dose and doses above 10 mg per 
day are not thought to provide significant additional benefit37. For this reason, the maximal dose of 
glibenclamide used in our program is 10 mg per day.  
 
Glibenclamide does carry a higher risk of hypoglycemia compared to newer sulfonylureas such as glimepiride 
and glipizide. However, glibenclamide was selected for use in this program because other sulfonylureas are 
either not readily available in Guatemala or are prohibitively expensive compared to glibenclamide. In 
addition, though glibenclamide carries a higher hypoglycemia risk than other sulfonylureas, the risk of serious 

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hypoglycemia (requiring the assistance of another person or hospitalization) is still low, with reported 
occurrence in only 0.5% of patients in a meta-analysis of sulfonylurea studies38.  
 
The application will recommend aspirin for patients with a history of ischemic stroke and CAD to prevent 
recurrent events and for patients with possible ACS, as long as contraindications are not present. The dose 
used for ASCVD prevention is 81 mg per day, which is in accordance with current consensus guidelines39,40. 
The dosage used for treatment of possible ACS is 324 mg, also in accordance with current consensus 
guidelines41,42. 
2.7 Potential Risk and Benefits to Subjects 
2.7.1 Known Potential Risks 
 
Immediate risks 
● 
The potential immediate risks include the risks of taking metformin, glibenclamide, or aspirin, medications 
which have been in use for decades and have well-established safety and side-effect profiles. 
○ 
Metformin: The most common side effect of metformin is gastrointestinal distress (e.g. dyspepsia, 
nausea, vomiting, diarrhea). This usually improves with time and most patients can tolerate these 
side effects, with only 5% of patients discontinuing the drug completely because of them36. The 
most serious reported adverse effect of metformin is lactic acidosis. However, the incidence of 
this has been found repeatedly to be exceedingly low. In fact, a 2010 Cochrane review found no 
cases of lactic acidosis over 70,490 patient-years of metformin use, even when patients with 
some renal impairment were included43. Finally, metformin can cause vitamin B12 deficiency with 
long term use 
○ 
Glibenclamide: The primary potential adverse effect of glibenclamide is hypoglycemia. The 
proportion of patients taking glibenclamide who will suffer an episode of severe hypoglycemia 
(requiring the assistance of another for treatment and/or hospitalization) is estimated to be 0.5%38 
○ 
Aspirin: Significant potential adverse effects of aspirin include gastrointestinal toxicity, 
hemorrhage, renal toxicity, and hypersensitivity reactions 
● 
Risk of errors in medication administration or recommendations due to user error or application 
malfunction 
● 
Discomfort with finger sticks for blood glucose and hemoglobin A1c measurements 
 
Long-range risks 
● 
Complications of medication adverse effects (e.g. anemia from metformin or aspirin use, renal 
insufficiency as a related to aspirin use) 
 
Reproductive risks: Pregnant women are excluded from the diabetes treatment program. However, it is 
possible that a woman of reproductive age could enroll without knowledge of current pregnancy or prior to 
becoming pregnant. Metformin is a class B drug in pregnancy (generally considered to be safe) and both 
metformin and glibenclamide have been used in the treatment of gestational diabetes, so their use would not 
be expected to engender risks other than those already described for the general population. In addition to 
the risks described above, which apply to a pregnant woman, aspirin also carries potential fetal risks of 
mortality, intrauterine growth retardation, salicylate intoxication, bleeding abnormalities, and neonatal 
acidosis. However, low dose aspirin, which is used in this program for the prevention of ASCVD in selected 
patients, is increasingly recommended for a number of different indications during pregnancy, including 
prevention of preeclampsia and continuation of aspirin therapy for prevention of stroke40. 
 
The risks of using these medications and the use of the application are justified by the fact that the patients in 
rural villages whom we are targeting would not otherwise have access to any consistent diabetes care. Not 
only this, but the care they do receive is often discontinuous and fragmented and the dose of medication or 
even which medication (glibenclamide or metformin) a patient receives depends on medication supply and the 

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whim of the untrained health promoter or pharmacist. In this way, we anticipate that the risks of application-
guided care will be less than the status quo. 
 
We anticipate that our approach could also be adapted to resource-limited settings around the world, with the 
potential to extend diabetes and other chronic disease care to patients who do not currently have access to 
this care due to critical shortages in health system workforce capacity. The knowledge gained by this and 
subsequent studies to advance this cause warrants the potential risks.  
 
Of the medications we will be utilizing, glibenclamide likely has the highest potential for harm. We did consider 
using other sulfonylureas which are thought to have a lower risk of hypoglycemia. However, as mentioned in 
section 2.6, alternate sulfonylureas are not reliably available in Guatemala and/or are prohibitively expensive. 
In addition, glibenclamide is one of the most widely-used sulfonylureas (and antidiabetic medications in 
general) worldwide44. Thus, the use of glibenclamide in this study may make our approach more 
generalizable.  
 
We also considered the timing of implementation for dosing changes recommended by the application: in 
real-time during the visit with retrospective approval by the physician supervisor within 1-2 days or 
subsequent to physician approval of application recommendations. We ultimately decided that the logistics of 
requiring physician approval of application recommendations prior to dispensing medications would be 
prohibitively complicated and would likely lead to patients going without medications for significant periods of 
time, possibly leading to complications. In essence, the physician has “pre-approved” the medication changes 
because these are made according to an algorithm designed and tested by physicians and approved by the 
San Lucas Mission medical director. Additionally, CHWs will be able to consult their coordinator and/or the 
medical director via telephone at the point of care if there are any questions about medication dosing or other 
recommendations given by the application. 
 
2.7.2 Protection Against Risks 
 
The risks of side effects from medications will be mitigated by several mechanisms: 
● 
As decreased renal function increases the risk of adverse effects of metformin and glibenclamide, renal 
function testing will be required prior to administration of medications for patients with a history of kidney 
disease and recommended for patients with hypertension and/or duration of diabetes of 10 years or 
greater. Glibenclamide and metformin will not be used for patients with eGFR <30 mL/min.  
● 
Patients will be asked about adverse effects of metformin monthly. Patients who are taking glibenclamide 
will also be asked about hypoglycemia symptoms and medication will be down-titrated if these symptoms 
are present 
● 
Patients above the age of 65 will have a less stringent treatment goal of A1c ≤8%, in accordance with 
ADA guidelines32. 
● 
Medication will only be up-titrated at 1 month checks when blood glucose is significantly above glycemic 
goals: FBG >180 mg/dL or PPBG >300 for patients below age 65 and FBG >200 mg/dL or PPBG >300 
for patients 65 or older or with multiple comorbidities 
● 
For aspirin use, patients will be asked about history of aspirin allergy in potentially emergent situations 
(when patient presenting with chest pain that could represent ACS) and aspirin will not be administered to 
patients with history of allergy. In non-emergent situations, patients will be asked both about history of 
allergy and signs of GI bleeding (blood in stool or black and tarry stools) prior to dispensing aspirin. 
 
The risks of POC finger stick testing will be minimized by CHW training emphasizing sterile technique and 
standard precautions. 
 
The risks posed by application malfunction or incorrect use will be mitigated by an intensive alpha testing 
process (systematically testing each possible scenario prior to implementation with patients to ensure correct 

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recommendations are given in every case), training of CHWs and physician oversight of application 
treatment recommendations and CHW decisions regarding medication administration and referrals.  
 
Exit criteria for the study includes the following: 
● 
Patient with eGFR <30 mL/min will be unable to safely take metformin or glibenclamide and thus will be 
excluded from the program. These patients will be referred to San Lucas Mission Hospital (SLMH) for 
consultation with Dr. Rafael Tun regarding alternate medication therapy. 
● 
Women who are found to be pregnant during the study 
● 
Patients who require insulin or additional medication other than metformin or glibenclamide for diabetes 
control 
 
Patients with mild adverse effects, such as gastrointestinal upset from metformin or mild hypoglycemia or 
hypoglycemia symptoms on glibenclamide will have their medication adjusted according to the titration 
algorithms used by the application. Patients who are unable to tolerate metformin or glibenclamide due to 
adverse effects will be referred to Dr. Rafael Tun for assessment and further treatment recommendations.  
Patients with more severe adverse effects, such as severe hypoglycemia (defined as resulting in alteration in 
mental status and requiring assistance from a CHW) or hypoglycemia not responsive to initial measures in 
the field will be transferred to SLMH via ambulance for further care.  
 
The program will pay the costs related to ambulance transfer to SLMH and the cost of treatment for 
medication adverse effects. Patients may incur costs from treatment for other complications of diabetes that 
fall outside the scope of the program, though this care is highly subsidized through the SLMH.  
2.7.3 Potential Benefits to the Subjects 
The primary potential benefit to patients is improved control of diabetes and avoidance of complications and 
premature death from this disease. Patients will also receive free medications and diabetes-related tests 
(blood glucose, A1c, and renal function testing if needed) while they are participating in the study. In 
addition, monthly visits will be an opportunity for patients to socialize and form supportive relationships with 
other patients with diabetes in their communities, which may contribute to an improvement in overall health 
and wellbeing.  
 
 
3 Study Objectives and Purpose 
● 
Primary Objective: Implement a CHW-led diabetes program to improve diabetes care in the rural 
communities surrounding San Lucas Tolimán, Guatemala 
● 
Primary Objective: To assess the efficacy of CHWs equipped with a smartphone application on improving 
glycemic control in patients living in rural communities in Guatemala 
● 
Secondary Objective: To assess the ability of CHWs equipped with a smartphone application to identify 
potential complications of diabetes in patients living in rural communities in Guatemala 
● 
Secondary Objective: To assess the safety of diabetes medication titration by CHWs equipped with a 
smartphone application 
 
4 Study Design and Endpoints 
4.1 General Design  
Design: This study is a single group, pre-and post-test feasibility/pilot study 
 
The expected duration of subject participation from enrollment to study completion (including follow up) is 12 
months  
 

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Summary of trial periods: 
● 
Enrollment: Months 0-6 (enrollment will be rolling) 
● 
Safety analyses will occur on a monthly basis during the trial (evaluation of data from monthly visits) 
● 
Evaluation of endpoints will first occur at 6 months post enrollment (6-12 months after study initiation for 
most participants). Participants will be followed up to 12 months post enrollment (12-18 months after 
study initiation for most participants) if possible based on program logistics and funding. Endpoints would 
again be assessed at that time  
4.1.1 Primary Study Endpoints 
The primary endpoints will be hemoglobin A1c at 6 months and 12 months post-enrollment. This will be 
analyzed and reported in two ways: 
● 
Mean hemoglobin A1c in the study group compared to mean value at baseline 
● 
Percentage of patients meeting treatment goal for hemoglobin A1c compared to this percentage 
at baseline. Treatment goal will be A1c ≤7 for most patients, A1c ≤8 for patients age 65 or older 
or who have 2 or more comorbidities, or other individualized goal for select patients as 
determined by the medical director (Dr. Rafael Tun)  
4.1.2 Secondary Study Endpoints 
● 
Mean A1c and proportion of patients at goal at 3 months and 9 months.  
● 
Mean FBG at 6 and 12 months compared to baseline value 
● 
Mean BMI at 6 and 12 months compared to baseline 
● 
Mean waist circumference at 6 and 12 months compared to baseline 
● 
Mean blood pressure at 6 and 12 months compared to baseline 
● 
Number and percentage of patients identified as potentially having the following complications:  
○ 
Angina 
○ 
Foot ulcers 
○ 
Ophthalmologic complications 
○ 
Hypertension 
● 
Percentage of patients successfully completing referrals for potential complications  
● 
Number of patients referred for poor glycemic control or intolerance of diabetic medications and 
percentage of these patients who complete referral 
● 
Prevalence of adverse effects of metformin and hypoglycemia symptoms throughout the study 
● 
Patient medication adherence throughout the study and at 6 and 12 months compared to baseline 
● 
CHW compliance with medication recommendations provided by the application (proportion of visits) 
4.1.3 Primary Safety Endpoints 
● 
Documented hypoglycemia (blood glucose <70 mg/dL) 
● 
Hypoglycemia requiring emergency transport to the hospital and/or hospitalization 
● 
Instances in which the application provided an incorrect recommendation 
● 
Patient death 
5 Study Subjects – Enrollment and Withdrawal 
 
5.1 Subject Population  
 
Subjects will include adults 18 years of age and older and will be recruited from the 19 rural villages 
surrounding San Lucas Tolimán, Guatemala. Treatment of children with diabetes entails greater complexity 
and is beyond the scope of this program. Though there are no enrollment restrictions based on race or 
ethnicity, the majority of the people living in these villages are from the Kaqchikel ethnic group, an indigenous 
Mayan people of the midwestern highlands of Guatemala. 

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5.2  Inclusion Criteria  
 
Inclusion Criteria  
1 
Willing to provide written informed consent  
2 
Willing to comply with all study procedures and be available for the duration of the study  
3 
Male or female, at least 18 years of age 
4 
Prior diagnosis of type 2 diabetes  
5 
Resident of one of the rural communities served by the CHW network of San Lucas Tolimán  
 
5.3 Exclusion Criteria 
 
Exclusion Criteria 
1. Type 1 diabetes 
2. Women who are pregnant 
3. Current use of insulin 
4. Renal insufficiency (eGRF <30 mL/min/1.73 m2) 
5. Unable to provide informed consent 
 
5.4 Subject Screening for Recruitment  
5.4.1 Subject Identification 
 
Potential subjects will be identified by CHWs from their prior knowledge of individuals with diabetes in 
their communities. We also anticipate that study participation will be bolstered by word of mouth 
communication between patients in the communities. Patients may also be identified during mobile 
medical clinics run by visiting medical volunteers.  
5.4.2 Recruitment and Retention Strategies 
 
Potential participants will be contacted in person by CHWs. At that time, the health promoter will ask if 
they would like to participate in the study. We anticipate that more than women than men will enroll in the 
study based on prior experience of the CHWs in other health promotion programs. Men’s availability is 
often less than women’s because of their occupations (agricultural work with long and inflexible hours, 
long commutes or residential work in population centers). The communities we are working in are 
ethnically homogenous, so recruitment of minorities is not relevant. We anticipate recruiting around 150 
patients. 
5.5 Vulnerable Populations 
 
TABLE 1: Vulnerable populations included and excluded from this study: 
 
Include 
Exclude 
Vulnerable Population Type 
 
X 
Adults unable to consent 
 
X 
Individuals who are not yet adults (e.g. infants, children, teenagers) 
 
X 
Wards of the State (e.g. foster children) 
 
X 
Pregnant women 
 
X 
Prisoners 

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5.5.1  Subject Capacity 
 
We anticipate that all subjects will have the capacity to provide informed consent. Patients who are not 
able to consent will not be included in the study. 
5.5.2  Subject/Representative Comprehension 
 
CHWs will use the “teach back” method 45 to assess subject comprehension of the potential risks and 
benefits of study participation.  
5.6 
Informed Consent 
The PI will be responsible for ensuring that valid consent is obtained and documented for all subjects 
unless the IRB waives the requirement for documentation of informed consent for all or part of the study 
5.6.1 Process of Consent 
 
CHWs will obtain consent from each subject. The consent will be obtained during CHW visit for health 
care, either at the patient’s residence or the clinical meeting site for their community. Consent forms will 
be translated into Spanish by Dr. Duffy, who is fluent in Guatemalan Spanish and has been certified to 
see Spanish-speaking patients independently by UW Interpreter Services.  Consent discussion will 
primarily occur in Spanish. Most patients speak Spanish and Kaqchikel, a Mayan language, so some part 
of the consent discussion may occur in Kaqchikel as all CHWs are bilingual Spanish and Kaqchikel 
speaking. Most CHWs and patients are not literate in Kaqchikel, only Spanish, so the consent form will 
not be translated into Kaqchikel.  
 
The amount of time given for the consent discussion will take approximately ten minutes but may last as 
long as necessary to ensure patient understanding of the study. The participant will be given as much 
time as needed to make a decision. All staff will undergo project specific training that includes methods of 
obtaining consent. These methods include thorough explanation of the study, risks and benefits of 
participation, emphasis of voluntary participation and withdrawal at any time, assurance that non-
participation will not affect health care and provision of adequate time for independent decision. 
 
Consent will be documented on paper forms, which will be stored in a locked receptacle either at SLMH 
or at the CHW headquarters in the village of Quixaya.  
5.6.2 Consent Form (see templates for UW-Madison) 
 
See in ARROW 
5.6.3 HIPAA 
Information about study subjects will be kept confidential and managed according to the requirements of 
the Health Insurance Portability and Accountability Act of 1996 (HIPAA). Attached/submitted as part of 
our application is a signed subject authorization form that includes:  
 
● 
The collection of the following protected health information (PHI) 
○ 
Identifying information: name, date of birth, community 
○ 
Past medical history and current medical problems 
○ 
Your treatment for diabetes 
○ 
Measurements: height, weight, waist circumference, vital signs 
○ 
Lab results, including blood glucose and hemoglobin A1c 
○ 
Information about symptoms and medical problems related to diabetes 

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● 
Access of this information by CHWs to provide diabetes care and carry out the program, SLMH Medical 
Director Dr. Rafael Tun to provide supervision of CHWs and oversight of treatment decisions, by the 
study investigators to supervise the study and analyze program efficacy and study results, and by the IRB 
for study monitoring and supervision.  
● 
The patient can revoke their authorization if they decide to withdraw from the study 
5.6.4 Revoking Consent 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by regulation, 
retains the ability to use all information collected prior to the revocation of subject authorization.  For 
subjects that have revoked authorization to collect or use PHI, attempts will be made to obtain permission 
to collect at least vital status (i.e. that the subject is alive) at the end of their scheduled study period. 
5.6.5  Costs to the Subject 
 
The cost of study medications used in the program, POC and other lab testing and supplies, CHW labor 
costs, emergency transport of patients to SLMH as needed, and treatment of adverse effects from study 
medication (e.g. hypoglycemia) will be covered by funding from a Global Health Seed Grant from the UW 
Global Health Institute. In general, care provided at SLMH is free or very low cost, but patients may be 
responsible for the cost of care provided outside of the study protocols (payment for this care will not 
come from study grant funding).  
5.6.6 Payment for Participation 
 
Patients will receive free diabetes care through the study program, including medications, testing, 
emergency transportation to SLMH, and treatment of medication adverse effects as needed. There will be 
no additional compensation.  
 
5.7 Early Withdrawal of Subjects 
5.7.1 Premature termination of study 
 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause. Written notification, documenting the reason for study suspension or termination, will be provided 
by the PI or co-investigator to the IRB. If the study is prematurely terminated or suspended, the PI will 
promptly inform the IRB and will provide the reason(s) for the termination or suspension.  
 
Circumstances that may warrant termination or suspension include, but are not limited to:  
● 
Determination of unexpected, significant, or unacceptable risk to participants  
● 
Demonstration of efficacy that would warrant stopping  
● 
Insufficient compliance to protocol requirements  
● 
Data that are not sufficiently complete and/or evaluable  
● 
Determination of futility  
 
Study may resume once concerns about safety, protocol compliance, data quality are addressed and 
satisfy the IRB. 
5.7.2 When and How to Withdraw Subjects 
. 
Subjects may be withdrawn from the study in the following scenarios: 
● 
Subject consent withdrawal 

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● 
Subject becomes pregnant 
● 
Subject unable to take metformin or glibenclamide due to adverse effects or development of 
severe renal dysfunction (eGFR <30mL/min/173 m2) 
● 
Subject requires insulin or other alternative treatment for diabetes 
● 
Clinical discretion of the site medical director, Dr. Tun 
 
When subjects are withdrawn from the study, they will be promptly referred to Dr. Rafael Tun at SLMH for 
continuing diabetes and other appropriate medical care. 
5.7.3    Data Collection and Follow-up for Withdrawn Subjects 
 
Data collected prior to withdrawal will be included in the study.  
6 Study Agent 
6.1 Description and Formulation 
 
In this study, we will be using a smartphone application which we designed to guide CHWs through the 
clinical assessment of patients with diabetes including collection of demographic data and past medical 
history, assessment of medication history, adherence, and adverse effects, measurement of glycemic control, 
screening for complications, medication administration and titration, and patient counseling. This application 
will run in the web-browser of an Android smartphone. This application is IDE exempt. 
 
The medications we will be using are as follows: 
● 
Metformin HCl regular-release 850 mg tablets 
● 
Glibenclamide (glyburide) regular-release 5 mg tablets 
● 
Aspirin 81 mg tablets 
 
6.2 Packaging 
 
Metformin and glibenclamide come in blister packages of 10 tablets each. Aspirin comes in a bottle. 
6.3 Preparation, Administration and Storage of Study Drug 
No preparation of the study drugs is necessary. They will be stored in a storage locker at the CHW 
headquarters in Quixaya, San Lucas Tolimán, Guatemala.  
6.4 Route of Administration 
All medications are administered by mouth. Patients will be treated with at least one of the three 
medications during the entire duration of the study and their participation in the diabetes treatment program 
(so, at least 6 months), aside from patients who may be observed off of medication to see if their diabetes 
is diet-controlled. Whether a patient is taking one of these medications or not depends on their individual 
characteristics, including glycemic control and targets, experience of side effects, and medication 
adherence, as described by the treatment protocols outlined below and in the appendices.   
6.5 Starting Dose and Dose Escalation Schedule 
 
Metformin will be started at 850 mg once daily and increased to the target dose of 1700 mg after 2 weeks. 
If not meeting treatment goals after ≥1 month, metformin can be increased to 2550 mg. Patients who are 
unable to tolerate the 1700 mg dose will take the 850 mg dose. 
 

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Glibenclamide will be used for patients who are unable to tolerate metformin, in addition to metformin if A1c 
≥9, or if glycemic goals not met despite maximal dose of metformin. Dosing will start at 2.5 mg once per 
day. If glycemic goals are not met after ≥1 month, dose will be escalated to 5 mg once per day and then 10 
mg once per day as needed.  
 
Aspirin will be dosed at 81 mg once per day for secondary prevention in eligible patients with history of MI 
or stroke or patients who have new chest pain and are awaiting medical workup for possible CAD. Patients 
with high risk chest pain and possible ACS will be treated with aspirin 324 mg (four 81 mg tablets) once 
while awaiting emergency transport to SLMH. 
 
Please consult Appendix 8, Appendix 10, and Appendix 11 for further information on medication titration 
protocols 
6.6 Dose Adjustments/Modifications/Delays 
See 6.5 above and relevant appendices  
6.7 Prior and Concomitant Therapy/ Standard of Care 
Some patients may already be taking metformin and/or glibenclamide prior to enrollment. Their doses will 
be adjusted based on glycemic goals, current control, medication adherence, and medication side effects. 
Patients may require additional medication therapy or other treatment for complications of diabetes or other 
health problems while they are participating in the study. The only medication that would preclude them 
from further participation in the study would be if they needed to start insulin for uncontrolled diabetes or 
emergence of a contraindication to metformin or glibenclamide.  
6.8 
Randomization and Blinding of Study Drug 
 
This section is not necessary as this study is not a randomized or blinded trial.  
 
6.9 Receiving, Storage, Dispensing and Return or Disposal of Study Agent  
 
Table 2: Study Agent information at a glance: 
 
Name 
Source 
Storage  
Dispensing 
Disposal 
Metformin 850 mg 
tab 
Drogueria Americana 
CHW 
headquarters 
CHWs 
NA 
Glibenclamide 
5 
mg tab 
NeoEthicals 
“ “ 
“ “ 
NA 
Aspirin 81 mg tab 
Drogueria Americana or 
NeoEthicals 
“ “  
“ “ 
NA 
 
6.9.1 Receipt of Drug Supplies 
Metformin, glibenclamide, and aspirin will be obtained from Drogueria Americana and NeoEthicals, S.A., 
two reputable pharmaceutical distributors operating in Guatemala City with whom SLM has worked for 
some time.  
 
An inventory will be performed and a drug receipt log filled out and signed by the person accepting the 
shipment.  The designated study staff will count and verify that the shipment contains all the items noted 
in the shipment inventory.  

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6.9.2 Storage 
Storage of medications will occur in a storage locker in the CHWs’ headquarters in Quixaya. As such, 
they will not be exposed to sunlight or extremes of temperature. In the temperate climate of highland 
Guatemala, temperatures will not routinely vary from the 68-77 degree F storage temperature range and 
excursions would not exceed the 59 to 86 degrees F recommended for these medications29–31 
 
6.9.3 Dispensing 
Medications will be dispensed to each patient at monthly visits by CHWs as guided by the diabetes 
smartphone application. Adherence to medication will be assessed at each monthly visit by standardized 
patient report (see Appendix 3 for more information on how adherence assessment). 
6.9.4 Return or Disposal 
Unused medication at the end of the study will remain with the SLM CHW program to be used by patients 
continuing in SLM’s diabetes treatment program.  
 
7 Study Procedures 
7.1 LABS 
 
All patients will have POC HbA1c testing performed at baseline and every 3 months. The ADA does recommend 
individualization of A1c testing, advising quarterly checks in patients not meeting glycemic goals and at least twice 
yearly in those meeting treatment goals32. While we do intend to implement individualized testing in the diabetes 
program after the study period, testing will be every 3 months for all patients during the study period to allow for 
more uniform evaluation of program efficacy at the predetermined times of endpoint analysis (6 and 12 months for 
primary endpoints).  
 
A1c testing will be performed with A1CNow®+ (PTS Diagnostics) POC capillary blood analyzers. This analyzer 
has been granted a CLIA waiver and has been certified by the National Glycohemoglobin Standardization 
Program (NGSP)46.  
 
Capillary blood glucose measurements will be conducted at baseline and monthly using the Bayer Contour® POC 
system. This is also CLIA-waived and has been validated in comparisons with plasma/serum glucose analyzers. 
 
Both aforementioned POC testing systems are designed to be used by laypeople and patients without medical 
training, making them very appropriate for use by frontline health workers, as in our study. 
 
Testing of serum creatinine will be checked at baseline for all patients with prior history of chronic kidney disease 
prior to administration of metformin or glibenclamide. Baseline creatinine will also be strongly recommended for 
patients with hypertension (defined as either taking antihypertensives or baseline BP ≥140/90) and/or duration 
since diagnosis of diabetes of 10 years or more. Serum creatinine will be checked at SLMH and reviewed by the 
medical director, who will then determine patient eligibility for metformin and/or glibenclamide therapy based on 
calculated eGFR.  
 
Ideally, serum creatinine would be tested in all patients at baseline and prior to administration of metformin and 
glibenclamide. However, this is not performed routinely for diabetic patients in the San Lucas area due to the 
expense and availability of travel. Requiring testing for all patients prior to administration would likely severely 
restrict participation as it is likely many patients would not travel to San Lucas to have necessary testing done and 
subsequently be lost to follow up. For this reason, we have adopted a risk-factor based targeted testing strategy 
for checking renal function.  

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7.2 Established Standard of Care:  
The current standard of care in the rural communities around San Lucas Tolimán is not consistent. There is a 
clinic based at SLMH in San Lucas Tolimán, which sees a group of ~100 patients, usually on a monthly basis. 
These patients are by and large from the city itself, as it is very difficult for patients from the rural communities to 
spare the time and expense to travel to San Lucas. This clinic is run by the two supervisors of the CHW program, 
who have significant experience in working with patients with diabetes and can titrate metformin and 
glibenclamide if blood glucose is persistently elevated. SLMH CHWs also hold clinics 3 of the 19 rural 
communities. However, supplies of medications and testing supplies are inconsistent and thus patients are 
administered medications based more on which medication and dosage is available rather than based on clinical 
judgement and patient condition. The CHWs staffing these rural clinics are unable to titrate diabetes medications 
in response to persistent hyperglycemia or adverse effects. Services at all of these clinics are limited to 
measurement of vital signs, blood glucose (when supplies available), dispensing of metformin and glibenclamide, 
counseling on diet and lifestyle, and referral to SLMH medical director Dr. Rafael Tun if complications are 
suspected based on CHW clinical judgement. No further laboratory testing or other assessment is routinely 
performed.  
 
7.3 Study Visits 
7.4.1 Screening/Baseline:  
 
Training of CHWs 
While not an element of direct patient care, an essential part of the diabetes program will be the training of CHWs 
prior to enrollment of patients. CHWs undergo a 6 week training program emphasizing health education and 
identification of patients who require definitive medical care. Many also have experience in using a mobile 
application to track and treat children with chronic malnutrition. However, many lack specific training on the 
management and complications of diabetes. We have designed training to fill in these gaps in diabetes-specific 
knowledge and to teach CHWs how to use the smartphone application and POC testing devices. We will also 
instruct CHWs on human subjects research ethics and the process of obtaining informed consent, as they will act 
as collaborating investigators.  
 
Training will consist of the following elements (allotted times are approximate): 
● 
Didactic sessions focusing on the basics of diabetes pathophysiology, lifestyle and medication 
management, and complications - 8 hours total. The PowerPoint presentation that will used for these 
session has been uploaded to ARROW in the Supplemental Information section.  
● 
Didactic session on human subjects research protections and informed consent - 2 hours. We will use 
adapted CITI training that was developed by researchers from Marywood University on a prior research 
project performed with the SLM CHWs. These researchers have given us permission to use these 
materials, which are available in English and Spanish. As many of the CHWs have already reviewed this 
material, the reuse of this resource will have the added benefit of reinforcing their prior learning. The 
training documents are uploaded in the ARROW application.  
● 
Practical workshop on the use of POC testing devices (A1CNow®+ and Contour® devices), measurement 
of blood pressure and pulse using the ReliOn™ BP200 automatic blood pressure cuff, body temperature 
using a digital thermometer, and anthropometric measurements (weight, height, waist circumference) - 4 
hours 
● 
Hands-on practice with the application with trainers taking on the role of patients to simulate patient 
encounters - 8 hours 
 
Training will be conducted by study investigators with the assistance of CHW program coordinators, who have 
already gone through such training in order to carry out beta testing of the application with a small group of 
patients. We anticipate training approximately 30 CHWs for the diabetes program. As the program matures, the 
CHW coordinators will gradually take over more responsibility for CHW training to ensure local ownership and 
sustainability of the program (a “train the trainers” model). 

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For the first several months after completion of the training program, CHWs will be paired with one of the CHW 
coordinators while seeing patients for continued clinical mentorship and guidance.  
 
Enrollment Visit 
Patients will be screened for study eligibility on the same day of potential enrollment. If they are eligible, informed 
consent will be obtained and the CHW will proceed with enrollment and initial treatment of the patient with the 
guidance of the enrollment module of the smartphone application. The enrollment visit will consist of the following 
elements: 
 
● 
Screening questions (Appendix 1) - Determine if patient is eligible to participate in the study. Done with 
verbal consent. If eligible, written and verbal consent obtained for full study participation and CHW 
proceeds to the next step.  
● 
Collection of demographic information and relevant past medical history (Appendix 1) - This information 
facilitates the creation of a patient database and clinical registry, determines the patient’s glycemic goal 
and if they need renal function testing prior to initiation of medications, and informs a decision about 
chronic aspirin therapy for secondary ASCVD prevention (Appendix 2). Glycemic goals are generally 
consistent with ADA guidelines32 and are determined as follows: 
○ 
Patients <65 years old with <2 comorbidities (CAD, CVD, COPD, CKD, cancer) 
■ 
A1c goal ≤7% 
■ 
FBG 80-130 mg/dL 
■ 
PPBG <180 mg/dL 
○ 
Patients ≥65 years old or <65 years old and with ≥2 comorbidities (as listed above) 
■ 
A1c goal ≤8% 
■ 
FBG 90-150 
■ 
PPBG <200 mg/dL 
 
● 
Medication history, adherence and side effects (Appendix 3) - This information factors into the 
confirmation of diabetes with A1c testing (for example, if a patient is not taking any medications and their 
A1c is 5.2, they may not have diabetes) and provides information for the application to determine starting 
medication for each patient. Information about whether a patient is taking medication for hypertension will 
also factor into whether renal function testing is recommended prior to initiating medication treatment.  
● 
Glycemic testing, vital signs, and other anthropometric data - Fasting status, defined as no caloric intake 
for the past 8 hours, is determined. Blood glucose and hemoglobin A1c are collected for each patient. If 
hypoglycemia or severe hyperglycemia are identified at this stage, the application initiates management 
protocols (Appendix 4 and Appendix 5). CHWs also measure blood pressure, pulse (also collected by the 
automatic BP cuff), height, weight, and waist circumference. Hypotension or hypertension are addressed 
according to the protocol described in Appendix 12 
● 
Screening for possible complications of diabetes (Appendix 6) - The application guides CHWs through an 
assessment for possible complications of diabetes, including diabetic foot ulcers, angina, and diabetic eye 
disease.  
● 
Recommendations for referrals (Appendix 7) - Based on information collected and entered by the CHW, 
the application will make recommendations regarding the need for a referral to SLMH and evaluation the 
medical director Dr. Tun. Referral recommendations are classified as emergent (recommended 
immediate transport), urgent (evaluation by physician within 1-2 days), or routine (evaluation by physician 
within 1-2 weeks). CHWs are prompted by the application to immediately arrange for referral and 
transport for emergent conditions (e.g. current chest pain suspicious for angina) as soon as these 
conditions are identified. The recommendation for referral in these cases is a “hard stop” and the CHW 
will not be able to proceed with application questions until the emergent situation is addressed and 

Diabetes Treatment in Rural Guatemala 
 
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definitive care arranged. These recommendations for referrals are consistent with the WHO protocol for 
diabetes management in low-resource settings47 
● 
Medication recommendations and counseling - Based on medication history, A1c, and glycemic goal, the 
application uses an algorithm to determine a recommended medication regimen for the patient, including 
the amount of medication to dispense (Appendix 8). The application provides information on how to take 
the medication and how to avoid adverse effects, which the CHW discusses with the patient (Appendix 9). 
The CHW then uses the “teach-back” method to ensure that the patient understands how to take their 
medication. The CHW will also provide patient education on diabetes self-management, including diet, 
physical activity, and foot care, with the assistance of demonstration materials developed for the program 
(uploaded to ARROW application in the Supplemental Information section).  
Physician Oversight 
Within 1-2 days of the enrollment visit and every subsequent visit, patient data from the smartphone application 
will be uploaded to a secure online database viewable to the supervising physician, Dr. Tun. Within 1 week of 
each visit, Dr. Tun will review the visit summary for each patient and either approve the current treatment or 
recommend changes to the treatment, including changes to the patient’s glycemic target as necessary. Also 
during that 1 week timeframe, any changes recommended by Dr. Tun will be communicated to the patient through 
the health promoter coordinators and/or the health promoter who saw the patient. 
If CHWs have questions regarding patient care while conducting a patient visit, they will contact one of the CHW 
coordinators and or Dr. Tun via telephone for advice on how to proceed.  
7.4.2 Follow up:  
 
Acceptable Window for Study Visits (including weekends) 
 
Visit 
Window 
Activities 
Monthly follow up visits 
+/- 1 week 
● Assessment of the following: 
○ Medication adherence and tolerance 
○ Glycemic control with blood glucose 
○ Presence of diabetes complications 
● Refill of medications, with titration of dosage as needed 
● Diabetic education 
Month 3 visit 
+/- 1 week 
Same as for monthly visit with the exception that A1c is 
checked (if indicated) in addition to blood glucose and is 
used for medication titration  
 
Monthly Visits 
CHWs will meet with patients once per month to follow up on adherence and tolerance to medications, assess 
glycemic control, assess for complications of diabetes, refill medications (with dosing adjustments as needed for 
side effects, non-adherence or poor glycemic control), and provide diabetic education. These monthly visits will be 
facilitated by the smartphone application monthly protocol. This protocol mirrors the enrollment protocol as 
described above, with the following exceptions: 
 
● 
Basic demographic information and medical history are not reassessed. This information is carried 
forward from the enrollment visit 
● 
Blood glucose alone is collected. A1c is not collected unless it was recommended to be done the month 
prior and was not collected at that time 
● 
Algorithms for medication adjustments are based on blood glucose, preferencing fasting glucose over 
postprandial glucose (Appendix 10) 
 
Month 3 Visit 

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At every 3rd monthly visit, starting with the visit 3 months after enrollment, A1c will be assessed. When A1c is 
checked, the month 3 medication titration algorithm (Appendix 11), is used rather than the monthly titration 
algorithm, which uses blood glucose. This protocol also considers the current glucose measurement to account 
for cases in which glycemic control may have improved significantly in the past month due to medication or 
lifestyle changes, but A1c may still be above goal due to earlier hyperglycemia. For example, if a patient with A1c 
goal of 7 has an A1c of 7.5, but FBG of 105, the application will recommend that the patient continues with the 
current medication dosing rather than recommending a dose increase. Other than checking A1c and using the 
A1c-based algorithm as indicated, the procedures performed at the month 3 visit are identical to those of the 
monthly visit.  
7.4.3 Unscheduled: 
 
The CHWs live in the same communities as the patients they will be serving. As such, we recognize that patients 
may come to them with concerns outside of the structure of monthly visits as described above. We have designed 
an additional module for the smartphone application that guides the CHWs through an assessment for 
hypoglycemia or severe hyperglycemia and possible complications of diabetes. This module uses the same 
relevant protocols from the enrollment and monthly visits (see Appendix 4, Appendix 5, Appendix 6, Appendix 12). 
If a patient or CHW has a concern outside of the scope of these protocols, the CHW will contact a CHW 
coordinator and/or the medical director Dr. Tun for guidance.  
 
7.4.4 Final Study Visit 
 
All patients will be followed until at least 6 months post enrollment. Safety monitoring will occur on a continuous 
basis during the study and an interim analysis of efficacy will occur at the 6 month point. If permitted based on 
funding and personnel availability and the ability and desire of our local partners in Guatemala, patients will be 
continued to be followed out to 12 months post enrollment.  
 
This study is based around the implementation of a program that the San Lucas Mission intends to continue 
indefinitely. Thus, patients who participated in this study will have the opportunity to continue their treatment 
through the CHW-led diabetes program. The study will inform a quality improvement process for this program and 
work to ensure program sustainability.  
8 Study Analysis 
8.1 Sample Size Determination 
 
For this study, we plan to recruit approximately 150 patients based on the known population of diabetics in the 
rural communities surrounding San Lucas Tolimán. Of these, we hope to enroll at least 100 patients in the study. 
Using these numbers, statistical power was calculated using the UCSF online sample size calculators 48 for a 
one-group before-after study. The following parameters were used for calculation: 
 
● 
ɑ = 0.050 
● 
β = 0.200 
● 
SD for outcome = 2.4 (this was the reported pretreatment SD for A1c for a population of 174 indigenous 
diabetics upon enrollment in a diabetes treatment program in rural Guatemala) 
● 
Within-subject A1c correlation coefficient (rwithin) of 0.928 (this is based on an analysis conducted to 
determine the accuracy and precision of the A1CNow®+ testing device49, which we are using in our study) 
● 
Sample size = 100 
 
With this sample size, we will have adequate power to detect an effect size as small as 0.257% A1c and should 
easily be able to detect more clinically significant differences of 1% A1c or more. 
 

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Another primary outcome will be the proportion of patients meeting treatment goals vs this proportion at baseline. 
Using the above website, the same parameters for ɑ and β, sample size of 100, and a baseline proportion of 
patients meeting treatment goals of 13% (this is based on a needs assessment that we conducted as part of this 
project), we would have 80% power to detect a proportion of 30.2% of patients with good glycemic control (OR 
2.896 compared to baseline). 
8.2 Statistical Methods 
 
The primary endpoints will be hemoglobin A1c at 6 months and 12 months post-enrollment. This will be analyzed 
and reported in two ways: 
● 
Mean hemoglobin A1c in the study group compared to mean value at baseline 
● 
Percentage of patients meeting treatment goal for hemoglobin A1c compared to this percentage at 
baseline. Treatment goal will be A1c ≤7 for most patients, A1c ≤8 for patients age 65 or older or who have 
2 or more comorbidities, or other individualized goal for select patients as determined by the medical 
director (Dr. Rafael Tun)  
 
Secondary endpoints and analyses will include: 
● 
Mean A1c and proportion of patients at goal at 3 months and 9 months. 
● 
Mean FBG at 6 and 12 months compared to baseline value 
● 
Mean BMI at 6 and 12 months compared to baseline 
● 
Mean waist circumference at 6 and 12 months compared to baseline 
● 
Mean blood pressure at 6 and 12 months compared to baseline 
● 
Number and percentage of patients identified as potentially having the following complications:  
○ 
Ischemic chest pain 
○ 
Foot ulcers 
○ 
Ophthalmologic complications 
○ 
Hypertension 
● 
Percentage of patients successfully completing referrals for potential complications  
● 
Number and percentage of patients referred for poor glycemic control or intolerance of diabetic 
medications and percentage of these patients who complete referral 
● 
Prevalence of adverse effects of metformin and hypoglycemia symptoms throughout the study 
● 
Patient medication adherence throughout the study and at 6 and 12 months compared to baseline 
(proportion patient reporting each level of adherence) 
● 
CHW compliance with medication recommendations provided by the application (proportion of visits) 
 
Differences in continuous variables (e.g. mean A1c) will be analyzed using paired, 2-tailed t tests. Differences in 
categorical values (e.g. percentage of patients meeting treatment goal for A1c) will be analyzed using the 
McNemar test for binary matched-pairs data.  
8.3 Subject Population(s) for Analysis 
 
There will be no randomization and there is only one group, so all patients enrolled will be analyzed to the extent 
of their participation. Analyses will be as described above in section 8.2. Planned subgroup analyses include 
patients with A1c less than or equal to treatment goal at baseline, patients above treatment goal at baseline, and 
patients with A1c ≥9 at baseline. 
 
8.4 Planned Interim Analysis:  
 
Initial analysis of primary endpoints and safety endpoints will occur at 3 months post enrollment to determine if 
any significant changes are needed to treatment protocols.  

Diabetes Treatment in Rural Guatemala 
 
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9 Data Collection, Handling and Record Keeping 
9.1 Data Confidentiality 
 
A service known as CommCare is being used to collect data. Whenever data is transmitted between one of the 
servers CommCare uses and the Android application, it is sent using HTTPS. Here are the standards 
incorporated: 
● 
Encrypted server-client connections using HTTPS 
● 
All access to the cloud infrastructure is protected behind a firewall and require unique VPN access 
permissions 
● 
Data is transferred through channels monitored by intrusion monitoring systems 
● 
Encrypted at-rest database and encrypted database backups every night 
● 
Security management meets ISO 27001, PCI-DSS, SOC1, SOC2, SOC3, and HIPAA standards 
 
The devices used to collect data are encrypted Android smartphones. The CommCare mobile application itself is 
password protected and data collected by the application is encrypted (AES 256-Bit Symmetric Encyption, fully 
HIPAA compliant). These are only connected to the internet when data is being uploaded via a WIFI connection. 
Currently the devices are only being used by the health promoters the days of the diabetes checks, which is 
usually just 2 or 3 days per month. As soon as all the checks have been completed the devices are returned to 
the health promoter main building where the data is sent using a WIFI connection and then erased from the 
device. 
 
The data is stored with other hospital system data used in monitoring an infant nutrition program in a HIPAA 
compliant server (see above). This data essentially constitutes an aspect of the patient’s medical record at the 
San Lucas Mission Hospital. Persons with access to this database will include SLM medical director Dr. Tun, the 
coordinators of the CHW program, Alejandro Chavez (onsite data manager and software engineer), Dr. Svenson 
(the PI), and Dr. Duffy (co-investigator).  
 
Any hard copies of study data will be stored in locked filing cabinets at CHW headquarters in Quixaya and/or San 
Lucas Mission Hospital. When not in use, smartphones will be stored in a locked cabinet at CHW headquarters in 
Quixaya. 
 
Data used for analysis of study outcomes will be extracted from this secure online medical record and stored on a 
secure UW Health (DFMCH) server in a password-protected Access database and/or password-protected Excel 
files. Data may also be sent to UW Health email using the Stanford University secure email service, which is 
HIPAA compliant. This data will not be de-identified. This data will be shared securely with IRB personnel as 
needed for study monitoring.  
 
9.1.1 Confidentiality of Subject Records 
By signing the protocol, the Investigator agrees that an IRB representative may consult and/or copy study 
documents in order to verify CRF data. By signing the consent form, the subject agrees to this process. If study 
documents will be photocopied during the process of verifying CRF information, the subject will be identified by 
unique code only and full names and similar identifying information (such as medical record number or social 
security number) will be masked. 
 
The Clinical Site Investigators will ensure that the identity of subjects will be protected. All study records will be 
maintained in a secure fashion with access limited to essential study personnel only. All study documents 
submitted to the Coordinating Center will have identifiers removed other than dates of birth and service and 
subjects will be identified with a study-specific identification number only. The Clinical Site Investigators will 
maintain, in a secure location, an enrollment log that includes subject identifying information and links subjects to 
their study-specific identification number.  
 
Forma-ed: Add space between paragraphs of the same
style,  No bullets or numbering
Deleted: ONA 
Deleted: ONA 
Deleted: web browser of the device
Deleted: ¶
Deleted: TLS/
Deleted: <#>A+ certified server-client TLS 
configuration¶
Deleted: using AES-256 
Deleted: ISO 27001 security management 
certification via AWS data centers
Deleted: amazon web server
Deleted: a 

Diabetes Treatment in Rural Guatemala 
 
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Version #: 1.0 
9.2 Data Capture  
9.2.1 Source Documents 
The primary source documents used for this study will be the electronic forms generated by the diabetes 
smartphone application, which contain all clinical data entered by CHWs during enrollment and monthly visits. For 
patients who are referred to San Lucas Mission Hospital for emergency care or other reasons germane to the 
diabetes program, paper medical records generated by these encounters will also be evaluated.  
 
9.2.2 Case Report Forms 
Case report forms will be based on the electronic forms generated by the diabetes smartphone application. 
9.2.2.1 
Missing Data 
The smartphone application will assist in ensuring complete data entry in that most fields are required before the 
CHW can proceed to the next section of the visit and most data is entered through the use of radio buttons, pre-
populated list options, and parameter-limited text boxes. Retention and follow up of patients will be enhanced by 
visiting patients who miss monthly group visits at their homes. Only patients who completed follow up to each 
relevant time point (e.g. 6 months, 12 months) will be included in these analyses. 
9.2.3 Data Collection Tools 
We will not be using UW institutional data collection tools.  
9.3 
Data Management 
Data constituting patients’ medical records will be stored in a secure database as noted in section 9.1. Data used 
for research purposes will be derived from this clinical database and managed by Dr. Duffy. This will be stored on 
a secure UW Health server in password-protected files.  
9.4 
Data Monitoring  
The smartphone application used to carry out the protocols of the study and collect data has built-in consistency 
and range checks. Alejandro Chavez will upload patient data to the secure database after each round of patient 
visits and maintain the database. Site medical director Dr. Tun will review patient data for clinical supervision on a 
monthly basis, as will Dr. Duffy for safety and outcome monitoring. Dr. Duffy will meet with Alejandro Chavez at 
least every 2 weeks via Skype and as needed via email. Alejandro is in contact with Dr. Tun and the CHW 
coordinators on a daily basis. Dr. Duffy will also meet with Dr. Tun and the CHW coordinators via Skype as 
needed.  
9.5 
Records Retention 
         Records will be kept for at least 7 years following the study 
 
9.6 
Specimen Banking 
 
Not applicable  
 
10   Assessment of Safety 
10.1 
Specifications of Safety Parameters 
 

Diabetes Treatment in Rural Guatemala 
 
Jim Svenson 
 
33 
Version #: 1.0 
● 
Documented hypoglycemia (blood glucose <70 mg/dL) 
● 
Hypoglycemia requiring emergency transport to the hospital and/or hospitalization 
● 
Instances in which the application provided an incorrect recommendation 
● 
Patient death 
10.1.1 Definition of Adverse Events (AE)  
Adverse event means any untoward medical occurrence associated with the use of an intervention in 
humans, whether or not considered intervention-related (21 CFR 312.32 (a)). 
 
For the purposes of this study, known and non-serious adverse effects of medications used in the study - 
metformin, glibenclamide, and aspirin - which have been used for decades and have well-established 
safety profiles, will not be considered adverse events. Examples of such non-serious adverse effects 
include gastrointestinal side effects of metformin and hypoglycemia symptoms associated with 
glibenclamide (without documented hypoglycemia).  
10.1.2  Definition of Serious Adverse Events (SAE)  
An adverse program effect will include any serious adverse effect on health or safety or any life-
threatening problem or death caused by, or associated with, the diabetes treatment program, if that effect, 
problem, or death was not previously identified in nature, severity, or degree of incidence in the 
investigational plan or application, or any other unanticipated serious problem associated with the 
program that relates to the rights, safety, or welfare of subjects. 
10.1.3 Definition of Unanticipated Problems (UP)  
OHRP considers unanticipated problems involving risks to participants or others to include, in general, any 
incident, experience, or outcome that meets all of the following criteria:  
● 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the IRB-approved research protocol and 
informed consent document; and (b) the characteristics of the participant population being studied;  
● 
Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and  
● 
Suggests that the research places participants or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized.  
 
This study will use the OHRP definition of UP. 
10.2 
Classification of an Adverse Event 
10.2.1 Severity of Event 
The following guidelines will be used to describe severity.  
 
Mild – Events require minimal or no treatment and do not interfere with the participant’s daily activities.  
Moderate – Events result in a low level of inconvenience or concern with the therapeutic measures. 
Moderate events may cause some interference with functioning.  
Severe – Events interrupt a participant’s usual daily activity and may require systemic drug therapy or 
other treatment. Severe events are usually potentially life-threatening or incapacitating. 
 
10.2.2 Relationship to Study Agent 
 
This study will use a binary assessment: 

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Diabetes Treatment in Rural Guatemala 
 
Jim Svenson 
 
36 
Version #: 1.0 
 
 
10.4.3 Unanticipated problem reporting  
Dr. Duffy will be responsible for creating and completing a UP report form. Incidents that meet the OHRP 
criteria for UPs will be reported promptly on the following timeline:  
● 
UPs that are SAEs will be reported to the IRB within 24 hours of the investigator becoming aware of 
the event. 
● 
Any other UP will be reported to the IRB within 10 days of the investigator becoming aware of the 
problem. 
 
The UP report will include the following information:  
● 
Protocol identifying information: protocol title and number, PI’s name, and the IRB project number; 
● 
A detailed description of the event, incident, experience, or outcome; 
● 
An explanation of the basis for determining that the event, incident, experience, or outcome represents 
an UP; 
● 
A description of any changes to the protocol or other corrective actions that have been taken or are 
proposed in response to the UP. 
  
10.4.4 Events of special interest  
Events of special interest include documented hypoglycemia, probable hypoglycemia (symptoms 
reported by patient without hypoglycemia documented by blood glucose measurement) that 
required assistance from another person for treatment and incorrect recommendations given by the 
smartphone application.  
10.4.5 Reporting of pregnancy  
CHWs will ask women at risk of pregnancy (defined as premenopausal and without history of surgical 
sterilization) at each visit if they have reason to believe they could be pregnant. If a patient believes they 
could be pregnant, then a pregnancy test will be performed. If pregnancy test is positive, this patient will be 
referred for care through SLMH and withdrawn from the study. This will be reported to Dr. Duffy, who will 
subsequently report to the IRB.  
SAE detected by CHW during visit 
Patient managed per protocol, 
including emergency transport if 
needed 
Dr. Duffy SAE report, which he 
submits to IRB and PI (Dr. Svenson) 
within 24 hours of his awareness of 
SAE  
Dr. Svenson signs off on SAE 
report within 7 days of receipt 
Patient evaluated by Dr. Tun within 0-
3 days 
Dr. Tun reports SAE to Dr. Duffy 
within 1 day of his evaluation 

Diabetes Treatment in Rural Guatemala 
 
Jim Svenson 
 
37 
Version #: 1.0 
10.5 
Study Halting Rules 
 
Study suspension and revision of protocols will be considered if it appears that an inordinate number of 
severe adverse events are occurring. In particular, study suspension will be considered if there is an 
excessive incidence of severe hypoglycemia (documented BG <70 requiring emergency transfer and/or 
hospitalization). Estimates of the incidence of severe hypoglycemia with glibenclamide use vary, with one 
study reporting incidence of 7.4 episodes per 1000 person-years52 and another reporting 57.7 episodes per 
1000 person-years53 (figure computed from study data). Given that we will enroll approximately 100 patients 
and follow them for 6-12 months, we will consider the occurrence of more than 3 episodes of severe 
hypoglycemia as warranting review of study protocols and consideration of study suspension.  
10.6 
Safety Oversight 
 
Dr. Duffy will review all patient data each month to identify patient safety issues. Any issues will be 
promptly discussed with site investigator and medical director, Dr. Tun, and with the PI, Dr. Svenson. 
Special attention will be given to the following potential safety issues: 
● 
Documented hypoglycemia. This includes those episodes requiring emergency patient transport 
(severe) and non-severe (those treated without complication in the field). While this is a known 
but side effect of glibenclamide, frequent occurrences in our patients may suggest the need for an 
alteration in our medication titration protocols 
● 
Severe probable hypoglycemia (patient reports hypoglycemia symptoms that required the 
assistance of another person to treat due to altered mental status)  
● 
Incorrect recommendations regarding medication dosing, management of complications, or 
recommendations for referral provided by the application 
● 
AEs and UPs as described above, which would also be reported to the IRB.  
Interim cumulative safety analysis will occur at 3 months, 6 months, and 9 months and final safety 
analysis at 12 months.  
10.7 
Unblinding Procedure 
Not applicable 
11 Study Monitoring, Auditing, and Inspecting 
11.1 
Medical Monitoring 
 
11.1.1 Study Monitoring Plan 
Clinical site monitoring is conducted to ensure that the rights and well-being of human subjects are 
protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct of the trial 
is in compliance with the currently approved protocol/amendment(s), with GCP, and with applicable 
regulatory requirement(s).  
● 
Dr. Duffy will perform both remote monitoring once per month and in-person monitoring at several 
points during the study. In-person monitoring will occur early in the study during the enrollment process 
to assist with CHW training and study logistics. He will again visit between 6 and 12 months post-
enrollment for data analysis and program evaluation and improvement. Monitoring will be targeted on 
clinical endpoints, adverse effects, identified complications of diabetes, and accuracy of application 
recommendations and CHW actions 
● 
Independent audits will not be conducted 
 

Diabetes Treatment in Rural Guatemala 
 
Jim Svenson 
 
38 
Version #: 1.0 
11.2 
Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or MOP requirements. The 
noncompliance may be either on the part of the participant, the investigator, or the study site staff. As a 
result of deviations, corrective actions are to be developed by the site and implemented promptly.  
These practices are consistent with ICH E6:  
● 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3  
● 
5.1 Quality Assurance and Quality Control, section 5.1.1  
● 
5.20 Noncompliance, sections 5.20.1, and 5.20.2.  
 
The site PI/co-investigator/staff will be responsible for continuous vigilance to identify and report 
deviations to the protocol. These will be reported within 14 working days of identification of the protocol 
deviation, or within 14 working days of the scheduled protocol-required activity. All deviations must be 
addressed in study source documents, reported to the IRB. Protocol deviations will be sent to the local 
IRB per their guidelines. The site PI/study staff is responsible for knowing and adhering to their IRB 
requirements. Further details about the handling of protocol deviations will be included in the MOP.  
 
11.2.1 Internal Data and Safety Monitoring Board 
There will be no formal DSMB. Study will be monitored as described in 11.1.1 and 10.6 and safety issues 
will be reported to the IRB.  
 
11.3 Auditing and Inspecting 
The investigator will permit study-related monitoring, audits, and inspections by the IRB (or their 
representatives) of all study related documents (e.g. source documents, regulatory documents, data 
collection instruments, study data etc.).  The investigator will ensure the capability for inspections of 
applicable study-related facilities (e.g. pharmacy, diagnostic laboratory, etc.). 
11.4 Subject Compliance Monitoring 
 
At each visit, CHWs will assess medication compliance via patient report (see Appendix 3). Compliance 
with medication for diabetes is accounted for in treatment protocols and titration of medications. For 
patients who are noncompliant, CHWs will emphasize the importance of compliance to the patient and 
work with the patient to improve compliance. Patients will not be withdrawn from the study for repeated 
noncompliance, as this would deny them diabetes treatment and decrease the real-world applicability of 
our findings. Nonadherence with diabetes medications is common, with studies suggesting that only 50-
75% of patients take more than 80% of their medication doses54. 
12 Ethical Considerations 
 
This protocol and any amendments will be submitted to a properly constituted independent Ethics Committee 
(EC) or Institutional Review Board (IRB), in agreement with local legal prescriptions, for formal approval of 
the study conduct.  The decision of the EC/IRB concerning the conduct of the study will be made in writing to 
the investigator and a copy of this decision will be provided to the sponsor before commencement of this 
study.  The investigator should provide a list of EC/IRB members and their affiliate to the sponsor. 
 
All subjects for this study will be provided a consent form describing this study and providing sufficient 
information for subjects to make an informed decision about their participation in this study.  See the 
ARROW application for a copy of the consent form.  This consent form will be submitted with the protocol for 
review and approval by the EC/IRB for the study.  The formal consent of a subject, using the EC/IRB-
approved consent form, must be obtained before that subject undergoes any study procedure.  The consent 

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

Diabetes Treatment in Rural Guatemala 
 
Jim Svenson 
 
50 
Version #: 1.0 
■ 
Message: “It is now in a normal range. The patient should eat a full meal to prevent the 
blood sugar from dropping again. Continue with the questions after the patient has 
eaten.” 
■ 
Recommendation: “Be vigilant and seek medical attention if you begin to feel bad. You 
should have someone with you for the rest of the day. Do not take your glibenclamide 
today” 
■ 
Application will lower dosage of glibenclamide 
○ 
Reading 3 <70 
■ 
Message: “It remains very low. The patient should eat something with sugar (candy, 
juice, coke) immediately if they are still alert and able to eat and drink. If they are not 
responding or very sleepy, sprinkle sugar under the tongue. Call the coordinator to 
arrange transport to the hospital for further treatment and monitoring” 
 
Appendix 5 - Hyperglycemia Protocols 
 
Hyperglycemia 
● 
400≤FBG<HI 
○ 
Urgent MD visit recommended in all cases 
■ 
Patient willing to go 
● 
Dispense 5 days’ worth of meds as a bridge based on 180(200)≤FBG<400 
recommendations (if monthly visit) or A1c (month 3 or enrollment) 
● 
Arrange appointment 
■ 
Patient unwilling to go 
● 
Dispense medications based on 180(200)≤FBG<400 recommendations (if 
monthly visit) or A1c (month 3 or enrollment) 
● 
Follow up in 1-3 days 
● 
FBG=HI 
○ 
Emergent visit recommended in all cases 
■ 
Patient willing to go → arrange emergency transport 
■ 
Patient not willing to go 
● 
Dispense medications based on 180(200)≤FBG<400 recommendations (if 
monthly visit) or A1c (month 3 or enrollment) 
● 
Follow up in 1 day 
● 
PPBG=HI 
○ 
“Is the patient unresponsive, very sleepy, or confused” (Y/N) 
■ 
If YES, emergency visit recommended 
● 
Patient willing to go → arrange emergency transport 
● 
Patient not willing to go 
○ 
Dispense medications based on 180(200)≤FBG<400 (if monthly visit) or 
A1c (month 3 or enrollment) recommendations 
○ 
Follow up later that day or the next day 
■ 
If NO 
● 
CHW advises patient to increase water intake 
● 
Dispense medications based on 180(200)≤FBG<400 recommendations (if 
monthly visit) or A1c (month 3 or enrollment) 
● 
Follow up with FBG in 1-3 days 

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Diabetes Treatment in Rural Guatemala 
 
Jim Svenson 
 
53 
Version #: 1.0 
○ 
Time frame: same day, as soon as possible 
○ 
CHW recommends emergency transport to patient 
○ 
CHW calls SLMH to arrange for ambulance transport of the patient 
 
Indications for referrals 
● 
Routine referrals 
○ 
Stage I hypertension (BP 140-160/90-100 mmHg) 
○ 
Non-infected diabetic ulcer 
○ 
Need for renal function testing 
○ 
A1c ≥9 despite maximal doses of metformin and glibenclamide for ≥3 months 
○ 
A1c ≥9 for 3 consecutive checks 
○ 
A1c above glycemic target, but less than 9 for 4 consecutive checks  
○ 
Recent chest pain, moderate risk (2 of 5 points17) 
○ 
Blood in stool or possible melena 
○ 
Patient has other symptoms not addressed by the program protocols 
● 
Urgent referrals 
○ 
Stage II hypertension (BP 160-200/100-120 mmHg) 
○ 
Possibly infected diabetic ulcer, no signs of systemic infection 
○ 
Worsening vision 
○ 
FBG detectable, but ≥400 
○ 
A1c ≥14 
○ 
Patient cannot tolerate minimum doses of metformin and/or glibenclamide 
○ 
Current chest pain, moderate risk (2 of 5 points) 
● 
Emergency referrals 
○ 
Severe hypertension (BP ≥200/120 mmHg) 
○ 
Fasting blood glucose undetectable high 
○ 
Postprandial/random blood glucose undetectable high with mental status changes 
○ 
Hypoglycemia associated with altered mental status 
○ 
Persistent hypoglycemia despite treatment in the field 
○ 
Current chest pain, high risk (≥3 of 5 points) 
○ 
Possibly infected diabetic ulcer with signs of systemic infection 
 
Appendix 8 - Enrollment Medication Dosing Recommendations 
A1c <5.7 
1. Not taking medications→ Does not have diabetes. Retest in A1c in 1 year 
2. Nonadherent with medications → May not have diabetes or may have diet-controlled diabetes. Stop 
medications and retest A1c in 3 months 
3. Taking metformin without problems 
a. Metformin 500-1000 mg → metformin 850 mg 
b. Metformin 1500-2550 mg → metformin 1700 mg 
4. Taking metformin with problems 
a. Metformin 500-850 mg, refuses to take metformin → Stop medications, retest in 3 months 
b. Metformin 500-850 mg, agrees to take metformin → metformin 850 mg 
c. Metformin 1000-1700 mg → metformin 850 mg 
                                                   
17 See Appendix 6 for further details of risk assessment in patients with chest pain 

Diabetes Treatment in Rural Guatemala 
 
Jim Svenson 
 
54 
Version #: 1.0 
d. Metformin 2000-2550 mg → metformin 1700 mg 
5. Taking glibenclamide, with or without hypoglycemia or hypoglycemia symptoms 
a. All doses → metformin 1700 mg  
6. Taking glibenclamide, previous problems with metformin 
a. All doses, agree to take metformin → metformin 850 mg 
b. All doses, refuses to take metformin → discontinue medications, recheck A1c in 3 months 
7. Taking glibenclamide with hypoglycemia or hypoglycemia symptoms, previous problems with metformin 
a. All doses, agrees to take metformin → metformin 850 mg 
b. All doses, refuses to take metformin → stop medications, recheck A1c in 3 months 
8. Taking metformin and glibenclamide, with or without hypoglycemia or hypoglycemia symptoms 
a. Metformin 500-1000 mg + glibenclamide any dose → metformin 850 mg 
b. Metformin 1500-2550 mg + glibenclamide any dose → metformin 1700 mg 
9. Taking metformin and glibenclamide, problems with metformin 
a. Metformin 500-850 mg + glibenclamide any dose, agrees to take metformin → metformin 850 mg 
b. Metformin 500-850 mg + glibenclamide any dose, refuses to take metformin → stop medications, 
recheck A1c in 3 months 
c. Metformin 1000-1700 mg + glibenclamide any dose → metformin 850 mg 
d. Metformin 2000-2550 mg + glibenclamide any dose → metformin 1700 mg 
10. Taking metformin and glibenclamide, with hypoglycemia or hypoglycemia symptoms, problems with 
metformin 
a. Metformin 500-850 mg + glibenclamide any dose, agrees to take metformin → metformin 850 mg 
b. Metformin 500-850 mg + glibenclamide any dose, refuses to take metformin → stop medications, 
recheck A1c in 3 months 
c. Metformin 1000-1700 mg + glibenclamide any dose → metformin 850 mg 
d. Metformin 2000-2550 mg + glibenclamide any dose → metformin 1700 mg 
 
5.7≤ A1c <6.5 
1. Not taking medications → Patient has prediabetes. Counsel on diet and exercise and retest yearly 
2. Nonadherent with medications → May have diabetes. Stop medications and recheck A1c in 3 months 
3. Taking metformin without problems 
a. Metformin 500-1000 mg → metformin 850 mg 
b. Metformin 1500-2550 mg → metformin 1700 mg 
4. Taking metformin with problems 
a. Metformin 500-850 mg, refuses to take metformin → Stop medications, retest A1c in 3 months 
b. Metformin 500-850 mg, agrees to take metformin → metformin 850 mg 
c. Metformin 1000-1700 mg → metformin 850 mg 
d. Metformin 2000-2550 mg → metformin 1700 mg 
5. Taking glibenclamide, with or without hypoglycemia or hypoglycemia symptoms 
a. All doses → metformin 1700 mg  
6. Taking glibenclamide, previous problems with metformin, with or without hypoglycemia or hypoglycemia 
symptoms 
a. All doses, agrees to take metformin → metformin 850 mg 
b. All doses, refuses to take metformin → stop medications, recheck A1c in 3 months 
7. Taking metformin and glibenclamide, with or without hypoglycemia or hypoglycemia symptoms 
a. Metformin 500-1000 mg + glibenclamide any dose → metformin 850 mg 
b. Metformin 1500-2550 mg + glibenclamide any dose → metformin 1700 mg 

Diabetes Treatment in Rural Guatemala 
 
Jim Svenson 
 
55 
Version #: 1.0 
8. Taking metformin and glibenclamide, problems with metformin, without hypoglycemia or hypoglycemia 
symptoms 
a. Metformin 500-850 mg + glibenclamide any dose, agrees to take metformin → metformin 850 mg 
b. Metformin 500-850 mg + glibenclamide any dose, refuses to take metformin → glibenclamide 2.5 
mg 
c. Metformin 1000-1700 mg + glibenclamide any dose → metformin 850 mg 
d. Metformin 2000-2550 mg + glibenclamide any dose → metformin 1700 mg 
9. Taking metformin and glibenclamide, with hypoglycemia or hypoglycemia symptoms, problems with 
metformin 
a. Metformin 500-850 mg + glibenclamide any dose, agrees to take metformin → metformin 850 mg 
b. Metformin 500-850 mg + glibenclamide any dose, refuses to take metformin → stop medications, 
recheck A1c in 3 months 
c. Metformin 1000-1700 mg + glibenclamide any dose → metformin 850 mg 
d. Metformin 2000-2550 mg + glibenclamide any dose → metformin 1700 mg 
 
6.5≤ A1c ≤Tx goal 
1. Not taking medications or nonadherent, no hypoglycemia or hypoglycemia symptoms, no problems with 
metformin → metformin 1700 mg 
2. Not taking medications or nonadherent, no hypoglycemia or hypoglycemia problems, problems with 
metformin 
a. Agrees to take metformin → metformin 850 mg 
b. Refuses to take metformin → glibenclamide 2.5 
3. Not taking medications or nonadherent, hypoglycemia or hypoglycemia symptoms, problems with 
metformin 
a. Agrees to take metformin → metformin 850 mg 
b. Refuses to take metformin, prescribed glibenclamide >2.5 mg → glibenclamide 2.5 mg 
e. Refuses to take metformin, prescribed glibenclamide 2.5 mg → MD consult 
4. Taking metformin without problems 
a. Metformin 500-1000 mg → metformin 850 mg 
b. Metformin 1500-2550 mg → metformin 1700 mg 
5. Taking metformin with problems 
a. Metformin 500-850 mg, agrees to take metformin → metformin 850 mg 
b. Metformin 500-850 mg, refuses to take metformin → glibenclamide 2.5 mg 
c. Metformin 1000-1700 mg → metformin 850 mg 
d. Metformin 2000-2550 mg → metformin 1700 mg 
6. Taking glibenclamide without problems 
a. All doses → metformin 1700 mg 
7. Taking glibenclamide without problems, previous problems with metformin 
a. Willing to take metformin  
i. 
Glibenclamide 2.5 mg → metformin 850 mg 
ii. 
Glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
iii. 
Glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
iv. 
Glibenclamide 15-20 mg → metformin 850 mg + glibenclamide 10 mg 
b. Refuses to take metformin 
i. 
Glibenclamide 2.5-10 mg → continue current dose of glibenclamide 
ii. 
Glibenclamide 15-20 mg → glibenclamide 10 mg 
8. Taking glibenclamide with hypoglycemia or hypoglycemia symptoms 

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a. All doses → metformin 1700 mg 
9. Taking glibenclamide with hypoglycemia or hypoglycemia symptoms, previous problems with metformin 
a. Agrees to take metformin 
i. 
Glibenclamide 2.5-5 mg → metformin 850 mg 
ii. 
Glibenclamide 10 mg → metformin 850 mg + glibenclamide 2.5 mg 
iii. 
Glibenclamide 15 mg → metformin 850 mg + glibenclamide 5 mg 
iv. 
Glibenclamide 20 mg → metformin 850 mg + glibenclamide 10 mg 
b. Refuses to take metformin 
i. 
Glibenclamide 2.5 mg → stop medications, recheck A1c in 3 months 
ii. 
Glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Glibenclamide 10 mg → glibenclamide 5 mg 
iv. 
Glibenclamide 15-20 mg → glibenclamide 10 mg 
10. Taking metformin and glibenclamide without problems 
a. Metformin 500-1000 mg + glibenclamide 2.5-10 mg → metformin 850 mg + current glibenclamide 
dose 
b. Metformin 500-1000 mg + glibenclamide 15-20 mg → metformin 850 mg + glibenclamide 10 mg 
c. Metformin 1500-2550 mg + glibenclamide 2.5-10 mg  → metformin 1700 mg + current 
glibenclamide dose 
d. Metformin 1500-2550 mg + glibenclamide 15-20 mg → metformin 1700 mg + glibenclamide 10 
mg 
11. Taking metformin and glibenclamide, problems with metformin 
a. Metformin 500-850 mg + glibenclamide 2.5-10 mg, agrees to take metformin →metformin 850 mg 
+ current glibenclamide dose 
b. Metformin 500-850 mg + glibenclamide 15-20 mg, agrees to take metformin →metformin 850 mg 
+ glibenclamide 10 mg 
c. Metformin 500-850 mg + glibenclamide 2.5-10 mg, refuses to take metformin → current 
glibenclamide dose 
d. Metformin 500-850 mg + glibenclamide 15-20 mg, refuses to take metformin → glibenclamide 10 
mg 
e. Metformin 1000-1700 mg + glibenclamide 2.5-10 mg → metformin 850 mg + current 
glibenclamide dose 
f. 
Metformin 1000-1700 mg + glibenclamide 15-20 mg → metformin 850 mg + glibenclamide 10 mg 
g. Metformin 2000-2550 mg + glibenclamide 2.5-10 mg  → metformin 1700 mg + current 
glibenclamide dose 
h. Metformin 2000-2550 mg + glibenclamide 15-20 mg → metformin 1700 mg + glibenclamide 10 
mg 
12. Taking metformin and glibenclamide with hypoglycemia or hypoglycemia symptoms  
a. Metformin 500-1000 mg + glibenclamide 2.5 mg → metformin 850 mg 
b. Metformin 500-1000 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
c. Metformin 500-1000 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
d. Metformin 500-1000 mg + glibenclamide 15-20 mg → metformin 850 mg + glibenclamide 10 mg 
e. Metformin 1500-2000 mg + glibenclamide 2.5 mg → metformin 1700 mg 
f. 
Metformin 1500-2000 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
g. Metformin 1500-2000 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
h. Metformin 1500-2000 mg + glibenclamide 15-20 mg → metformin 1700 mg + glibenclamide 10 
mg 
i. 
Metformin 2550 mg + glibenclamide 2.5 mg → metformin 2550 mg 

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Version #: 1.0 
j. 
Metformin 2550 mg + glibenclamide 5 mg → metformin 2550 mg + glibenclamide 2.5 mg 
k. Metformin 2550 mg + glibenclamide 10 mg → metformin 2550 mg + glibenclamide 5 mg 
l. 
Metformin 2550 mg + glibenclamide 15-20 mg → metformin 2550 mg + glibenclamide 10 mg 
13. Taking metformin and glibenclamide, with hypoglycemia or hypoglycemia symptoms, problems with 
metformin 
a. Agrees to take metformin 
i. 
Metformin 500-850 mg + glibenclamide 2.5 mg → metformin 850 mg 
ii. 
Metformin 500-850 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 
mg 
iii. 
Metformin 500-850 mg + glibenclamide 10 mg → metformin 850 mg+ glibenclamide 5 mg 
iv. 
Metformin 500-850 mg + glibenclamide 15-20 mg → metformin 850 mg + glibenclamide 
10 mg 
b. Refuses to take metformin 
i. 
Metformin 500-850 mg + glibenclamide 2.5 mg → stop medications, recheck A1c in 3 
months 
ii. 
Metformin 500-850 mg + glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Metformin 500-850 mg + glibenclamide 10 mg → glibenclamide 5 mg 
iv. 
Metformin 500-850 mg + glibenclamide 15-20 mg → glibenclamide 10 mg 
c. Metformin 1000-1700 mg + glibenclamide 2.5 mg → metformin 850 mg 
d. Metformin 1000-1700 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
e. Metformin 1000-1700 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
f. 
Metformin 1000-1700 mg + glibenclamide 15-20 mg → metformin 850 mg + glibenclamide 10 mg 
g. Metformin 2000-2550 mg + glibenclamide 2.5 mg → metformin 1700 mg 
h. Metformin 2000-2550 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
i. 
Metformin 2000-2550 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
j. 
Metformin 2000-2550 mg + glibenclamide 15-20 mg → metformin 1700 mg + glibenclamide 10 
mg 
 
Tx goal< A1c <9 
1. Not taking medications or nonadherent, no hypoglycemia or hypoglycemia symptoms, no problems with 
metformin → metformin 1700 mg 
2. Not taking medications or nonadherent, no hypoglycemia or hypoglycemia symptoms, problems with 
metformin 
a. Agrees to take metformin → metformin 850 mg + glibenclamide 2.5 mg 
b. Refuses to take metformin → glibenclamide 2.5 mg 
3. Not taking medications or nonadherent, hypoglycemia or hypoglycemia symptoms → metformin 1700 mg 
4. Not taking medications or nonadherent, hypoglycemia or hypoglycemia symptoms, problems with 
metformin 
a. Agrees to take metformin → metformin 850 mg 
b. Refuses to take metformin, prescribed glibenclamide >2.5 mg → glibenclamide 2.5 mg 
c. Refuses to take metformin, prescribed glibenclamide 2.5 mg → MD consult 
5. Taking metformin without problems 
a. Metformin 500-1000 mg → metformin 1700 mg 
b. Metformin 1500-2000 mg → metformin 2550 mg  
c. Metformin 2550 mg → metformin 2550 mg + glibenclamide 2.5 mg  
6. Taking metformin with problems 
a. Metformin 500-850 mg, agrees to take metformin → metformin 850 mg + glibenclamide 2.5 mg 

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b. Metformin 500-850 mg, refuses to take metformin → glibenclamide 2.5 mg 
c. Metformin 1000-1700 mg → metformin 850 mg + glibenclamide 2.5 mg 
d. Metformin 2000-2550 mg → metformin 1700 mg + glibenclamide 2.5 mg 
7. Taking glibenclamide without problems 
a. Glibenclamide 2.5-10 mg → metformin 1700 mg + glibenclamide current dose 
b. Glibenclamide 15-20 mg → metformin 1700 mg + glibenclamide 10 mg 
8. Taking glibenclamide, previous problems with metformin 
a. Agrees to take metformin 
i. 
Glibenclamide 2.5-10 mg → metformin 850 mg + glibenclamide current dose 
ii. 
Glibenclamide 15-20 mg → metformin 850 mg + glibenclamide 10 mg 
b. Refuses to take metformin 
i. 
Glibenclamide 2.5 mg → glibenclamide 5 mg 
ii. 
Glibenclamide 5 mg → glibenclamide 10 mg 
iii. 
Glibenclamide 10-20 mg → glibenclamide 10 mg 
9. Taking glibenclamide with hypoglycemia or hypoglycemia symptoms 
a. Glibenclamide 2.5 mg → metformin 1700 mg 
b. Glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg  
c. Glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
d. Glibenclamide 15-20 mg → metformin 1700 mg + glibenclamide 10 mg 
10. Taking glibenclamide with hypoglycemia or hypoglycemia symptoms, previous problems with metformin 
a. Agrees to take metformin 
i. 
Glibenclamide 2.5 mg → metformin 850 mg 
ii. 
Glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
iii. 
Glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
iv. 
Glibenclamide 15-20 mg → metformin 850 mg + glibenclamide 10 mg 
b. Refuses to take metformin 
i. 
Glibenclamide 2.5 mg → MD consult 
ii. 
Glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Glibenclamide 10 mg → glibenclamide 5 mg 
iv. 
Glibenclamide 15-20 mg → glibenclamide 10 mg 
11. Taking metformin and glibenclamide without problems 
a. Metformin 500-1000 mg + glibenclamide 2.5-10 mg → metformin 1700 mg + current 
glibenclamide dose 
b. Metformin 500-1000 mg + glibenclamide 15-20 mg → metformin 1700 mg + glibenclamide 10 mg 
c. Metformin 1500-2000 mg + glibenclamide 2.5-10 mg → metformin 2550 mg + glibenclamide 
current dose 
d. Metformin 1500-2000 mg + glibenclamide 15-20 mg → metformin 2550 mg + glibenclamide 10 
mg 
e. Metformin 2550 mg + glibenclamide 2.5 mg → metformin 2550 mg + glibenclamide 5 mg 
f. 
Metformin 2550 mg + glibenclamide 5 mg → metformin 2550 mg + glibenclamide 10 mg 
g. Metformin 2550 mg + glibenclamide 10-20 mg → metformin 2550 mg + glibenclamide 10 mg 
12. Taking metformin and glibenclamide, problems with metformin 
a. Agrees to take metformin 
i. 
Metformin 500-850 mg + glibenclamide 2.5 mg → metformin 850 mg + glibenclamide 5 
mg 
ii. 
Metformin 500-850 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 10 
mg 

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iii. 
Metformin 500-850 mg + glibenclamide 10-20 mg → metformin 850 mg + glibenclamide 
10 mg 
b. Refuses to take metformin 
i. 
Metformin 500-850 mg + glibenclamide 2.5 mg → glibenclamide 5 mg 
ii. 
Metformin 500-850 mg + glibenclamide 5 mg → glibenclamide 10 mg 
iii. 
Metformin 500-850 mg + glibenclamide 10-20 mg → glibenclamide 10 mg 
c. Metformin 1000-1700 mg + glibenclamide 2.5 mg → metformin 850 mg + glibenclamide 5 mg 
d. Metformin 1000-1700 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 10 mg 
e. Metformin 1000-1700 mg + glibenclamide 10-20 mg → metformin 850 mg + glibenclamide 10 mg 
f. 
Metformin 2000-2550 mg + glibenclamide 2.5 mg → metformin 1700 mg + glibenclamide 5 mg 
g. Metformin 2000-2550 mg + glibenclamide 5 mg→ metformin 1700 mg + glibenclamide 10 mg 
h. Metformin 2000-2550 mg + glibenclamide 10-20 mg → metformin 1700 mg + glibenclamide 10 
mg 
13. Taking metformin and glibenclamide with hypoglycemia or hypoglycemia symptoms 
a. Metformin 500-1000 mg + glibenclamide 2.5 mg → metformin 1700 mg 
b. Metformin 500-1000 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
c. Metformin 500-1000 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
d. Metformin 500-1000 mg + glibenclamide 15-20 mg → metformin 1700 mg + glibenclamide 10 mg 
e. Metformin 1500-2000 mg + glibenclamide 2.5 mg → metformin 2550 mg 
f. 
Metformin 1500-2000 mg + glibenclamide 5 mg → metformin 2550 mg + glibenclamide 2.5 mg 
g. Metformin 1500-2000 mg + glibenclamide 10 mg → metformin 2550 mg + glibenclamide 5 mg 
h. Metformin 1500-2000 mg + glibenclamide 15-20 mg → metformin 2550 mg + glibenclamide 10 
mg 
i. 
Metformin 2550 mg + glibenclamide 2.5 mg → metformin 2550 mg 
j. 
Metformin 2550 mg + glibenclamide 5 mg → metformin 2550 mg + glibenclamide 2.5 mg 
k. Metformin 2550 mg + glibenclamide 10 mg → metformin 2550 mg + glibenclamide 5 mg 
l. 
Metformin 2550 mg + glibenclamide 15-20 mg → metformin 2550 mg + glibenclamide 10 mg 
14. Taking metformin and glibenclamide, with hypoglycemia or hypoglycemia symptoms, problems with 
metformin 
a. Agrees to take metformin 
i. 
Metformin 500-850 mg + glibenclamide 2.5 mg → metformin 850 mg 
ii. 
Metformin 500-850 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 
mg 
iii. 
Metformin 500-850 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 
mg 
iv. 
Metformin 500-850 mg + glibenclamide 15-20 mg → metformin 850 mg + glibenclamide 
10 mg 
b. Refuses to take metformin 
i. 
Metformin 500-850 mg + glibenclamide 2.5 mg → MD consult 
ii. 
Metformin 500-850 mg + glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Metformin 500-850 mg + glibenclamide 10 mg → glibenclamide 5 mg 
iv. 
Metformin 500-850 mg + glibenclamide 15-20 mg → glibenclamide 10 mg 
c. Metformin 1000-1700 mg + glibenclamide 2.5 mg → metformin 850 mg 
d. Metformin 1000-1700 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
e. Metformin 1000-1700 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
f. 
Metformin 1000-1700 mg + glibenclamide 15-20 mg → metformin 850 mg + glibenclamide 10 mg 
g. Metformin 2000-2550 mg + glibenclamide 2.5 mg → metformin 1700 mg 

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h. Metformin 2000-2550 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
i. 
Metformin 2000-2550 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
j. 
Metformin 2000-2550 mg + glibenclamide 15-20 mg → metformin 1700 mg + glibenclamide 10 
mg 
 
9≤ A1c ≤14 
1. Not taking medications → metformin 1700 mg + glibenclamide 2.5 mg 
2. Not taking medications, problems with metformin 
a. Agrees to take metformin → metformin 850 mg + glibenclamide 2.5 mg 
b. Refuses to take metformin → glibenclamide 2.5 mg 
3. Not taking medications, hypoglycemia or hypoglycemia symptoms → metformin 1700 mg 
4. Not taking medications, hypoglycemia or hypoglycemia symptoms, problems with metformin 
a. Agrees to take metformin, prescribed glibenclamide >2.5 mg → metformin 850 mg + 
glibenclamide 2.5 mg 
b. Agrees to take metformin, prescribed glibenclamide 2.5 mg → metformin 850 mg 
c. Refuses to take metformin, prescribed glibenclamide >2.5 mg → glibenclamide 2.5 mg 
d. Refuses to take metformin, prescribed glibenclamide 2.5 mg → MD consult 
5. Taking metformin without problems 
a. Metformin 500-2000 mg → metformin 1700 mg + glibenclamide 2.5 mg 
b. Metformin 2550 mg → metformin 2550 mg + glibenclamide 2.5 mg  
6. Taking metformin with problems 
a. Metformin 500-850 mg, agrees to take metformin → metformin 850 mg + glibenclamide 2.5 mg 
b. Metformin 500-850 mg, refuses to take metformin → glibenclamide 2.5 mg 
c. Metformin 1000-1700 mg → metformin 850 mg + glibenclamide 2.5 mg 
d. Metformin 2000-2550 mg → metformin 1700 mg + glibenclamide 2.5 mg 
7. Taking glibenclamide without problems 
a. Glibenclamide 2.5-10 mg → metformin 1700 mg +glibenclamide current dose 
b. Glibenclamide 15-20 mg → metformin 1700 mg + glibenclamide 10 mg 
8. Taking glibenclamide without problems, previous problems with metformin 
a. Agrees to take metformin 
i. 
Glibenclamide 2.5-10 mg → metformin 850 mg + glibenclamide current dose 
ii. 
Glibenclamide 15-20 mg → metformin 850 mg + glibenclamide 10 mg 
b. Refuses to take metformin 
i. 
Glibenclamide 2.5 mg → glibenclamide 5 mg 
ii. 
Glibenclamide 5 mg → glibenclamide 10 mg 
iii. 
Glibenclamide 10-20 mg → glibenclamide 10 mg 
9. Taking glibenclamide with hypoglycemia or hypoglycemia symptoms 
a. Glibenclamide 2.5 mg → metformin 1700 mg 
b. Glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg  
c. Glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
d. Glibenclamide 15-20 mg → metformin 1700 mg + glibenclamide 10 mg 
10. Taking glibenclamide with hypoglycemia or hypoglycemia symptoms, previous problems with metformin 
a. Agrees to take metformin 
i. 
Glibenclamide 2.5 mg → metformin 850 mg 
ii. 
Glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
iii. 
Glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
iv. 
Glibenclamide 15-20 mg → metformin 850 mg + glibenclamide 10 mg 

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b. Refuses to take metformin 
i. 
Glibenclamide 2.5 mg →MD consult 
ii. 
Glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Glibenclamide 10 mg → glibenclamide 5 mg 
iv. 
Glibenclamide 15-20 mg → glibenclamide 10 mg 
11. Taking metformin and glibenclamide without problems 
a. Metformin 500-1000 mg + glibenclamide 2.5-10 mg → metformin 1700 mg + current 
glibenclamide dose 
b. Metformin 500-1000 mg + glibenclamide 15-20 mg → metformin 1700 mg + glibenclamide 10 mg 
c. Metformin 1500-2000 mg + glibenclamide 2.5-10 mg → metformin 2550 mg + glibenclamide 
current dose 
d. Metformin 1500-2000 mg + glibenclamide 15-20 mg → metformin 2550 mg + glibenclamide 
current dose 
e. Metformin 2550 mg + glibenclamide 2.5-10 mg → metformin 2550 mg + glibenclamide current 
dose 
f. 
Metformin 2550 mg + glibenclamide 15-20 mg → metformin 2550 mg + glibenclamide 10 mg 
12. Taking metformin and glibenclamide, problems with metformin 
a. Agrees to take metformin 
i. 
Metformin 500-850 mg + glibenclamide 2.5 mg → metformin 850 mg + glibenclamide 5 
mg 
ii. 
Metformin 500-850 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 10 
mg 
iii. 
Metformin 500-850 mg + glibenclamide 10-20 mg → metformin 850 mg + glibenclamide 
10 mg 
b. Refuses to take metformin 
i. 
Metformin 500-850 mg + glibenclamide 2.5 mg → glibenclamide 5 mg 
ii. 
Metformin 500-850 mg + glibenclamide 5 mg → glibenclamide 10 mg 
iii. 
Metformin 500-850 mg + glibenclamide 10-20 mg → glibenclamide 10 mg 
c. Metformin 1000-1700 mg + glibenclamide 2.5 mg → metformin 850 mg + glibenclamide 5 mg 
d. Metformin 1000-1700 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 10 mg 
e. Metformin 1000-1700 mg + glibenclamide 10-20 mg → metformin 850 mg + glibenclamide 10 mg 
f. 
Metformin 2000-2550 mg + glibenclamide 2.5 mg → metformin 1700 mg + glibenclamide 5 mg 
g. Metformin 2000-2550 mg + glibenclamide 5 mg→ metformin 1700 mg + glibenclamide 10 mg 
h. Metformin 2000-2550 mg + glibenclamide 10-20 mg → metformin 1700 mg + glibenclamide 10 
mg 
13. Taking metformin and glibenclamide with hypoglycemia or hypoglycemia symptoms 
a. Metformin 500-1000 mg + glibenclamide 2.5 mg → metformin 1700 mg 
b. Metformin 500-1000 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
c. Metformin 500-1000 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
d. Metformin 500-1000 mg + glibenclamide 15-20 mg → metformin 1700 mg + glibenclamide 10 mg 
e. Metformin 1500-2000 mg + glibenclamide 2.5 mg → metformin 2550 mg 
f. 
Metformin 1500-2000 mg + glibenclamide 5 mg → metformin 2550 mg + glibenclamide 2.5 mg 
g. Metformin 1500-2000 mg + glibenclamide 10 mg → metformin 2550 mg + glibenclamide 5 mg 
h. Metformin 1500-2000 mg + glibenclamide 15-20 mg → metformin 2550 mg + glibenclamide 10 
mg 
i. 
Metformin 2550 mg + glibenclamide 2.5 mg → metformin 2550 mg 
j. 
Metformin 2550 mg + glibenclamide 5 mg → metformin 2550 mg + glibenclamide 2.5 mg 

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k. Metformin 2550 mg + glibenclamide 10 mg → metformin 2550 mg + glibenclamide 5 mg 
l. 
Metformin 2550 mg + glibenclamide 15-20 mg → metformin 2550 mg + glibenclamide 10 mg 
14. Taking metformin and glibenclamide, with hypoglycemia or hypoglycemia symptoms, problems with 
metformin  
a. Agrees to take metformin 
i. 
Metformin 500-850 mg + glibenclamide 2.5 mg → metformin 850 mg 
ii. 
Metformin 500-850 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 
mg 
iii. 
Metformin 500-850 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 
mg 
iv. 
Metformin 500-850 mg + glibenclamide 15-20 mg → metformin 850 mg + glibenclamide 
10 mg 
b. Refuses to take metformin 
i. 
Metformin 500-850 mg + glibenclamide 2.5 mg → MD consult 
ii. 
Metformin 500-850 mg + glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Metformin 500-850 mg + glibenclamide 10 mg → glibenclamide 5 mg 
iv. 
Metformin 500-850 mg + glibenclamide 15-20 mg → glibenclamide 10 mg 
c. Metformin 1000-1700 mg + glibenclamide 2.5 mg → metformin 850 mg 
d. Metformin 1000-1700 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
e. Metformin 1000-1700 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
f. 
Metformin 1000-1700 mg + glibenclamide 15-20 mg → metformin 850 mg + glibenclamide 10 mg 
g. Metformin 2000-2550 mg + glibenclamide 2.5 mg → metformin 1700 mg 
h. Metformin 2000-2550 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
i. 
Metformin 2000-2550 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
j. 
Metformin 2000-2550 mg + glibenclamide 15-20 mg → metformin 1700 mg + glibenclamide 10 
mg 
 
A1c >14 OR FBG >400 
● 
Coordinator/MD consult for all cases 
 
 
Appendix 9 - Medication Instructions 
 
Metformin 850 mg50 
● 
For patients starting metformin 
○ 
Start taking one 850 mg tablet with breakfast 
○ 
After two weeks, start taking two tablets daily, one with breakfast and one with dinner 
● 
Dosing 
○ 
850 mg → take one tablet per day with breakfast 
○ 
1700 mg → take two tablets daily, one with breakfast and one with dinner 
○ 
2550 mg → take three tablets daily, one with breakfast, one with lunch, and one with dinner 
● 
Guidance for patients experiencing metformin GI side effects 
○ 
Always take metformin with food 
○ 
Try taking metformin at night, instead of in the morning 
○ 
Take half a tablet with breakfast and half a tablet with dinner (for patients taking one tablet per 
day) 

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Glibenclamide 5 mg68 
● 
Guidance for all patients → Take with breakfast or the main meal of the day at the same time each day. 
Should only be taken with food. Do not take on days that you are fasting, not able to eat, or if you 
will be eating significantly less food than you normally eat.  
● 
Dosing 
○ 
2.5 mg (starting dose) → Take ½ tablet (2.5 mg) once daily with breakfast or the first main meal 
of the day  
○ 
5 mg → take one tablet once daily with breakfast or the first main meal of the day 
○ 
10 mg → take two tablets daily with breakfast or the first main meal of the day 
 
Hypoglycemia teaching for patients taking glibenclamide69 
● 
Glibenclamide can cause low blood sugar, which sometimes can be dangerous 
● 
Low blood sugar can cause symptoms such as shaking/tremors, feeling confused, feeling uncoordinated, 
sweating a lot more than normal, feeling very anxious for no reason, or heart beating fast or irregular. 
These usually come on suddenly and happen when you haven’t eaten for a while, when doing hard 
physical work or exercising, or while drinking alcohol.  
● 
How to avoid low blood sugar 
○ 
Eat regular meals 
○ 
Take glibenclamide with the first main meal of the day and try to take at the same time each day. 
Do not taking if you will be fasting, not able to eat, or eating a lot less than you normally do.  
○ 
Eat a snack with carbohydrates before doing hard physical work or exercising 
○ 
Avoid drinking alcohol  
● 
If you think your blood sugar is low, you should eat or drink one of the following items: 
○ 
1 tablespoon of sugar 
○ 
6 hard candies 
○ 
2 tablespoons of raisins 
○ 
1 tablespoon of honey 
○ 
½ cup of fruit juice 
○ 
1 cup of skim milk 
○ 
½ cup of regular soda (not diet soda) 
● 
You should have at least one of these items with you when you leave the house so you can treat 
symptoms if you need to  
● 
Sometimes, a person with very low blood sugar becomes so confused or sleepy that they can’t eat or 
drink anything. Teach your family that if this happens to you, they should sprinkle sugar under your 
tongue and call for an ambulance right away.  
● 
Let your health promoter know if you are having symptoms of low blood sugar and if these get better 
when you eat or drink something with sugar. If someone had to help you because you were very sleepy 
or confused, you should get help right away. You should not take your glibenclamide again until you see 
your health promoter.  
 
Appendix 10 - Monthly Medication Dosing Recommendations 
 
 

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FBG <80 (<90)18 or PPBG<130(150) 
1. Metformin without problems, adherent → continue current doses 
2. Metformin without problems, nonadherent 
a. Metformin 850 mg → metformin 850 mg 
b. Metformin 1700-2550 mg → metformin 1700 mg 
3. Metformin with problems, adherent 
a. Metformin 850 mg, willing to continue → Metformin 850 mg 
b. Metformin 850 mg, not willing to continue → stop medications, check A1c when next indicated 
c. Metformin 1700 mg → metformin 850 mg 
d. Metformin 2550 mg → metformin 1700 mg 
4. Metformin with problems, nonadherent → same as #3 
5. Glibenclamide without problems, no previous problems with metformin, took yesterday → metformin 1700 
mg 
6. Glibenclamide without problems, no previous problems with metformin, did not take yesterday → 
metformin 1700 mg 
7. Glibenclamide without problems, previous problems with metformin, took yesterday 
a. Agrees to take metformin 
i. 
Glibenclamide 2.5-5 mg → metformin 850 mg 
ii. 
Glibenclamide 10 mg → metformin 850 mg + glibenclamide 2.5 mg 
b. Refuses to take metformin 
i. 
Glibenclamide 2.5 mg → stop medications, recheck A1c in 3 months 
ii. 
Glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Glibenclamide 10 mg → glibenclamide 5 mg 
8. Glibenclamide without problems, previous problems with metformin, did not take yesterday 
a. Agrees to take metformin → metformin 850 mg 
b. Refuses to take metformin → stop medications, recheck A1c in 3 months 
9. Glibenclamide with hypoglycemia or hypoglycemia symptoms, no previous problems with metformin, took 
yesterday → metformin 1700 mg 
10. Glibenclamide with hypoglycemia or hypoglycemia symptoms, no previous problems with metformin, did 
not take yesterday → metformin 1700 mg 
11. Glibenclamide with hypoglycemia or hypoglycemia symptoms, previous problems with metformin, took 
yesterday → same as #8 
12. Glibenclamide with hypoglycemia or hypoglycemia symptoms, previous problems with metformin did not 
take yesterday → same as #8 
13. Metformin and glibenclamide without problems, adherent, took glibenclamide yesterday 
a. Metformin 850 mg + glibenclamide any dose → metformin 1700 mg 
b. Metformin 1700-2550 mg + glibenclamide 2.5 mg → metformin 1700 mg 
c. Metformin 1700-2550 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
d. Metformin 1700-2550 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
14. Metformin and glibenclamide without problems, nonadherent, took glibenclamide yesterday → same as 
#13 
15. Metformin and glibenclamide without problems, adherent, did not take glibenclamide yesterday → 
metformin 1700 mg 
                                                   
18 Numbers in parentheses refer to the relevant measurements for patients who have relaxed glycemic goals (A1c 
≤8, FBG 90-150, PPBG <200) 

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16. Metformin and glibenclamide without problems, nonadherent, did not take glibenclamide yesterday → 
metformin 1700 mg 
17. Metformin and glibenclamide, problems with metformin, adherent, took glibenclamide yesterday 
a. Agrees to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5mg → metformin 850 mg 
ii. 
Metformin 850 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
b. Refuses to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → stop medications, recheck A1c in 3 months 
ii. 
Metformin 850 mg + glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → glibenclamide 5 mg 
c. Metformin 1700 mg + glibenclamide 2.5 mg → metformin 850 mg 
d. Metformin 1700 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 
e. Metformin 1700 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
f. 
Metformin 2550 mg + glibenclamide 2.5 mg → metformin 1700 mg 
g. Metformin 2550 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
h. Metformin 2550 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
18. Metformin and glibenclamide, problems with metformin, nonadherent, took glibenclamide yesterday → 
same as #17 
19. Metformin and glibenclamide, problems with metformin, adherent, did not take glibenclamide yesterday 
a. Metformin 850 mg + glibenclamide any dose, agrees to take metformin → metformin 850 mg 
b. Metformin 850 mg + glibenclamide any dose, refuses to take metformin → stop medications, 
recheck A1c in 3 months 
c. Metformin 1700 mg + glibenclamide any dose → metformin 850 mg 
d. Metformin 2550 mg + glibenclamide any dose → metformin 1700 mg 
20. Metformin and glibenclamide, problems with metformin, nonadherent, did not take glibenclamide 
yesterday → same as #19 
21. Metformin and glibenclamide, hypoglycemia or hypoglycemia symptoms, adherent, took glibenclamide 
yesterday 
a. Metformin 850 mg + glibenclamide any dose → metformin 1700 mg 
b. Metformin 1700 mg + glibenclamide 2.5-5 mg → metformin 1700 mg 
c. Metformin 1700 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 2.5 mg 
d. Metformin 2550 mg + glibenclamide 2.5-5 mg → metformin 2550 mg  
e. Metformin 2550 mg + glibenclamide 10 mg → metformin 2550 mg + glibenclamide 5 mg 
22. Metformin and glibenclamide, hypoglycemia or hypoglycemia symptoms, nonadherent, took 
glibenclamide yesterday 
a. Metformin 850 mg + glibenclamide any dose → metformin 1700 mg 
b. Metformin 1700-2500 mg + glibenclamide 2.5-5 mg → metformin 1700 mg 
c. Metformin 1700-2550 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 2.5 mg 
23. Metformin and glibenclamide, hypoglycemia or hypoglycemia symptoms, adherent, did not take 
glibenclamide yesterday 
a. Metformin 850-1700 mg + glibenclamide any dose → metformin 1700 mg 
b. Metformin 2550 mg + glibenclamide any dose → metformin 2550 mg 
24. Metformin and glibenclamide, hypoglycemia or hypoglycemia symptoms, nonadherent, did not take 
glibenclamide yesterday → metformin 1700 mg 
25. Metformin and glibenclamide, problems with metformin, hypoglycemia or hypoglycemia symptoms, 
adherent, took glibenclamide yesterday 

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a. Agrees to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5-5 mg → metformin 850 mg 
ii. 
Metformin 850 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 2.5 mg 
b. Refuses to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5-5 mg → stop medications, recheck A1c in 3 
months 
ii. 
Metformin 850 mg + glibenclamide 10 mg → glibenclamide 2.5 mg 
c. Metformin 1700 mg + glibenclamide 2.5-5 mg → metformin 850 mg 
d. Metformin 1700 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 2.5 mg 
e. Metformin 2550 mg + glibenclamide 2.5-5 mg → metformin 1700 mg 
f. 
Metformin 2550 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 2.5 mg 
26. Metformin and glibenclamide, problems with metformin, hypoglycemia or hypoglycemia symptoms, 
nonadherent, took glibenclamide yesterday → same as #25 
27. Metformin and glibenclamide, problems with metformin, hypoglycemia or hypoglycemia symptoms, 
adherent, did not take glibenclamide yesterday 
a. Metformin 850 mg + glibenclamide any dose, agrees to take metformin → metformin 850 mg 
b. Metformin 850 mg + glibenclamide any dose, refuses to take metformin → stop medications, 
recheck A1c in 3 months 
c. Metformin 1700 mg + glibenclamide any dose → metformin 850 mg 
d. Metformin 2550 mg + glibenclamide any dose → metformin 1700 mg 
28. Metformin and glibenclamide, problems with metformin, hypoglycemia or hypoglycemia symptoms, 
nonadherent, did not take glibenclamide yesterday → same as #27 
 
80(90)≤FBG≤130(150) or 130(150)≤PPBG<180(200) 
1. Metformin without problems, adherent → continue current doses 
2. Metformin without problems, nonadherent 
a. Metformin 850 mg → metformin 850 mg 
b. Metformin 1700-2550 mg → metformin 1700 mg 
3. Metformin with problems, adherent 
a. Metformin 850 mg, willing to continue → Metformin 850 mg 
b. Metformin 850 mg, not willing to continue → stop medications, check A1c when next indicated 
c. Metformin 1700 mg → metformin 850 mg 
d. Metformin 2550 mg → metformin 1700 mg 
4. Metformin with problems, nonadherent → same as #3 
5. Glibenclamide without problems, no previous problems with metformin, took yesterday → continue 
current dose 
6. Glibenclamide without problems, no previous problems with metformin, did not take yesterday → 
metformin 1700 mg 
7. Glibenclamide without problems, previous problems with metformin, took yesterday → continue current 
dose 
8. Glibenclamide without problems, previous problems with metformin, did not take yesterday 
a. Agrees to take metformin → metformin 850 mg 
b. Refuses to take metformin 
i. 
Glibenclamide 2.5 mg → stop medications, recheck A1c when next indicated 
ii. 
Glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Glibenclamide 10 mg → glibenclamide 5 mg 
9. Glibenclamide with hypoglycemia symptoms, no previous problems with metformin, took yesterday 

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a. Glibenclamide 2.5-5 mg → metformin 1700 mg 
b. Glibenclamide 10 mg → metformin 1700 mg + glibenclamide 2.5 mg 
10. Glibenclamide with hypoglycemia or hypoglycemia symptoms, no previous problems with metformin, did 
not take yesterday → metformin 1700 mg 
11. Glibenclamide with hypoglycemia symptoms, previous problems with metformin, took yesterday 
a. Agrees to take metformin 
i. 
Glibenclamide 2.5-5 mg → metformin 850 mg 
ii. 
Glibenclamide 10 mg → metformin 850 mg + glibenclamide 2.5 mg 
b. Refuses to take metformin 
i. 
Glibenclamide 2.5 mg → stop medications, check A1c when next indicated 
ii. 
Glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Glibenclamide 10 mg → glibenclamide 5 mg 
12. Glibenclamide with hypoglycemia symptoms, previous problems with metformin did not take yesterday 
a. Agrees to take metformin → metformin 850 mg 
b. Refuses to take metformin 
i. 
Glibenclamide 2.5-5 mg → stop medications, check A1c when next indicated 
ii. 
Glibenclamide 10 mg → glibenclamide 2.5 mg 
13. Metformin and glibenclamide without problems, adherent, took glibenclamide yesterday → continue 
current doses 
14. Metformin and glibenclamide without problems, nonadherent, took glibenclamide yesterday 
a. Metformin any dose + glibenclamide 2.5 mg → metformin 1700 mg 
b. Metformin any dose + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
c. Metformin any dose + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
15. Metformin and glibenclamide without problems, adherent, did not take glibenclamide yesterday 
a. Metformin any dose + glibenclamide 2.5mg → metformin current dose 
b. Metformin any dose + glibenclamide 5 mg → metformin current dose + glibenclamide 2.5 mg 
c. Metformin any dose + glibenclamide 10 mg → metformin current dose + glibenclamide 5 mg 
16. Metformin and glibenclamide without problems, nonadherent, did not take glibenclamide yesterday 
a. Metformin all doses + glibenclamide 2.5-5 mg → metformin 1700 mg 
b. Metformin all doses + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 2.5 mg 
17. Metformin and glibenclamide, problems with metformin, adherent, took glibenclamide yesterday 
a. Metformin 850 mg + any dose of glibenclamide, agrees to take metformin → continue current 
doses 
b. Metformin 850 mg + any dose of glibenclamide, refuses to take metformin → continue current 
dose of glibenclamide 
c. Metformin 1700 mg + glibenclamide any dose → metformin 850 mg + glibenclamide current dose 
d. Metformin 2550 mg + glibenclamide any dose → metformin 1700 mg + glibenclamide current 
dose 
18. Metformin and glibenclamide, problems with metformin, nonadherent, took glibenclamide yesterday → 
same as #17 
19. Metformin and glibenclamide, problems with metformin, adherent, did not take glibenclamide yesterday 
a. Agrees to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → metformin 850 mg 
ii. 
Metformin 850 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
b. Refuses to take metformin 

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i. 
Metformin 850 mg + glibenclamide 2.5 mg → stop medications, check A1c when next 
indicated 
ii. 
Metformin 850 mg + glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → glibenclamide 5 mg 
c. Metformin 1700 mg + glibenclamide 2.5 mg → metformin 850 mg 
d. Metformin 1700 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg  
e. Metformin 1700 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
f. 
Metformin 2550 mg + glibenclamide 2.5 mg → metformin 1700 mg  
g. Metformin 2550 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg  
h. Metformin 2550 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
20. Metformin and glibenclamide, problems with metformin, nonadherent, did not take glibenclamide 
yesterday 
a. Metformin 850 mg + glibenclamide any dose, agrees to take metformin → metformin 850 mg 
b. Refuses to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5-5 mg → stop medications, recheck A1c in 3 
months 
ii. 
Metformin 850 mg + glibenclamide 10 mg → glibenclamide 2.5 mg 
c. Metformin 1700 mg + glibenclamide 2.5-5 mg → metformin 850 mg 
d. Metformin 1700 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 2.5 mg 
e. Metformin 2550 mg + glibenclamide 2.5-5 mg → metformin 1700 mg 
f. 
Metformin 2550 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 2.5 mg 
21. Metformin and glibenclamide, hypoglycemia symptoms, adherent, took glibenclamide yesterday 
a. Metformin 850 mg + glibenclamide 2.5 mg → metformin 1700 mg 
b. Metformin 850 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
c. Metformin 850 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
d. Metformin 1700 mg + glibenclamide 2.5 mg → metformin 1700 mg 
e. Metformin 1700 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
f. 
Metformin 1700 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
g. Metformin 2550 mg + glibenclamide 2.5 mg → metformin 2550 mg 
h. Metformin 2550 mg + glibenclamide 5 mg → metformin 2550 mg + glibenclamide 2.5 mg 
i. 
Metformin 2550 mg + glibenclamide 10 mg → metformin 2550 mg + glibenclamide 5 mg 
22. Metformin and glibenclamide, hypoglycemia symptoms, nonadherent, took glibenclamide yesterday 
a. Metformin 850 mg + glibenclamide 2.5 mg → metformin 1700 mg 
b. Metformin 850 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
c. Metformin 850 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
d. Metformin 1700-2550 mg + glibenclamide 2.5 mg → metformin 1700 mg 
e. Metformin 1700-2550 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
f. 
Metformin 1700-2550 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
23. Metformin and glibenclamide, hypoglycemia symptoms, adherent, did not take glibenclamide yesterday 
a. Metformin 850-1700 mg + glibenclamide any dose → metformin 1700 mg 
b. Metformin 2550 mg + glibenclamide any dose → metformin 2550 mg 
24. Metformin and glibenclamide, hypoglycemia symptoms, nonadherent, did not take glibenclamide 
yesterday → metformin 1700 mg 
25. Metformin and glibenclamide, problems with metformin, hypoglycemia symptoms, adherent, took 
glibenclamide yesterday 
a. Agrees to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → metformin 850 mg 

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ii. 
Metformin 850 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
b. Refuses to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → stop medications, recheck A1c when next 
indicated 
ii. 
Metformin 850 mg + glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → glibenclamide 5 mg 
c. Metformin 1700 mg + glibenclamide 2.5 mg → metformin 850 mg  
d. Metformin 1700 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
e. Metformin 1700 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
f. 
Metformin 2550 mg + glibenclamide 2.5 mg → metformin 1700 mg  
g. Metformin 2550 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
h. Metformin 2550 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
26. Metformin and glibenclamide, problems with metformin, hypoglycemia symptoms, nonadherent, took 
glibenclamide yesterday → same as #25 
27. Metformin and glibenclamide, problems with metformin, hypoglycemia symptoms, adherent, did not take 
glibenclamide yesterday 
a. Taking metformin 850 mg + glibenclamide any dose, agrees to take metformin → metformin 850 
mg 
b. Refuses to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5-5 mg → Stop medications, recheck A1c when 
next indicated 
ii. 
Metformin 850 mg + glibenclamide 10 mg → glibenclamide 2.5 mg 
c. Metformin 1700 mg + glibenclamide any dose → metformin 850 mg 
d. Metformin 2550 mg + glibenclamide any dose → metformin 1700 mg 
28. Metformin and glibenclamide, problems with metformin, hypoglycemia or hypoglycemia symptoms, 
nonadherent, did not take glibenclamide yesterday → same as #27 
 
130(150)<FBG<180(200) or 180(200)≤PPBG<300 
1. Metformin without problems, adherent → continue current doses 
2. Metformin without problems, nonadherent → continue current doses 
3. Metformin with problems, adherent 
a. Metformin 850 mg, willing to continue → Metformin 850 mg 
b. Metformin 850 mg, not willing to continue → glibenclamide 2.5 mg 
c. Metformin 1700 mg → metformin 850 mg + glibenclamide 2.5 mg 
d. Metformin 2550 mg → metformin 1700 mg + glibenclamide 2.5 mg 
4. Metformin with problems, nonadherent 
a. Metformin 850 mg, willing to continue → metformin 850 mg 
b. Metformin 850 mg, not willing to continue → glibenclamide 2.5 mg 
c. Metformin 1700 mg → metformin 850 mg 
d. Metformin 2550 mg → metformin 1700 mg 
5. Glibenclamide without problems, no previous problems with metformin, took yesterday → continue 
current dose 
6. Glibenclamide without problems, no previous problems with metformin, did not take yesterday → continue 
current dose 
7. Glibenclamide without problems, previous problems with metformin, took yesterday → continue current 
dose 

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8. Glibenclamide without problems, previous problems with metformin, did not take yesterday → continue 
current dose 
9. Glibenclamide with hypoglycemia symptoms, no previous problems with metformin, took yesterday 
a. Glibenclamide 2.5 mg → metformin 1700 mg 
b. Glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
c. Glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
10. Glibenclamide with hypoglycemia or hypoglycemia symptoms, no previous problems with metformin, did 
not take yesterday 
a. Glibenclamide 2.5-5 mg → metformin 1700 mg 
b. Glibenclamide 10 mg → metformin 1700 mg + glibenclamide 2.5 mg 
11. Glibenclamide with hypoglycemia symptoms, previous problems with metformin, took yesterday 
a. Agrees to take metformin 
i. 
Glibenclamide 2.5 mg → metformin 850 mg 
ii. 
Glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
iii. 
Glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
b. Refuses to take metformin 
i. 
Glibenclamide 2.5 mg → MD consult 
ii. 
Glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Glibenclamide 10 mg → glibenclamide 5 mg 
12. Glibenclamide with hypoglycemia symptoms, previous problems with metformin, did not take yesterday 
a. Agrees to take metformin  
i. 
Glibenclamide 2.5-5 mg → metformin 850 mg 
ii. 
Glibenclamide 10 mg → metformin 850 mg + glibenclamide 2.5 mg 
b. Refuses to take metformin 
i. 
Glibenclamide 2.5 mg → MD consult 
ii. 
Glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Glibenclamide 10 mg → glibenclamide 5 mg 
13. Metformin and glibenclamide without problems, adherent, took glibenclamide yesterday → continue 
current doses 
14. Metformin and glibenclamide without problems, nonadherent, took glibenclamide yesterday → continue 
current doses 
15. Metformin and glibenclamide without problems, adherent, did not take glibenclamide yesterday → 
continue current doses 
16. Metformin and glibenclamide without problems, nonadherent, did not take glibenclamide yesterday 
a. Metformin all doses + glibenclamide 2.5mg → metformin current dose 
b. Metformin all doses + glibenclamide 5 mg → metformin current dose + glibenclamide 2.5 mg 
c. Metformin all doses + glibenclamide 10 mg → metformin current dose + glibenclamide 5 mg 
17. Metformin and glibenclamide, problems with metformin, adherent, took glibenclamide yesterday 
a. Metformin 850 mg + any dose of glibenclamide, agrees to take metformin → continue current 
doses 
b. Refuses to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → glibenclamide 5 mg 
ii. 
Metformin 850mg + glibenclamide 5-10 mg → glibenclamide 10 mg 
c. Metformin 1700 mg + glibenclamide 2.5 mg → metformin 850 mg + glibenclamide 5 mg 
d. Metformin 1700 mg + glibenclamide 5-10 mg → metformin 850 mg + glibenclamide 10 mg 
e. Metformin 2550 mg + glibenclamide 2.5 mg → metformin 1700 mg + glibenclamide 5 mg 
f. 
Metformin 2550 mg + glibenclamide 5-10 mg → metformin 1700 mg + glibenclamide 10 mg 

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18. Metformin and glibenclamide, problems with metformin, nonadherent, took glibenclamide yesterday 
a. Metformin 850 mg + any dose of glibenclamide, agrees to take metformin → continue current 
doses 
b. Refuses to take metformin → stop metformin, continue current dose of glibenclamide 
c. Metformin 1700 mg + glibenclamide any dose → metformin 850 mg + glibenclamide current dose 
d. Metformin 2550 mg + glibenclamide any dose → metformin 1700 mg + glibenclamide current 
dose 
19. Metformin and glibenclamide, problems with metformin, adherent, did not take glibenclamide yesterday → 
same as #18 
20. Metformin and glibenclamide, problems with metformin, nonadherent, did not take glibenclamide 
yesterday 
a. Agrees to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → metformin 850 mg 
ii. 
Metformin 850 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
b. Metformin 850 mg + glibenclamide any dose, refuses to take metformin → continue current dose 
of glibenclamide 
c. Metformin 1700 mg + glibenclamide 2.5 mg → metformin 850 mg  
d. Metformin 1700 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
e. Metformin 1700 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
f. 
Metformin 2550 mg + glibenclamide 2.5 mg → metformin 1700 mg  
g. Metformin 2550 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
h. Metformin 2550 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
21. Metformin and glibenclamide, hypoglycemia symptoms, adherent, took glibenclamide yesterday 
a. Metformin 850 mg + glibenclamide 2.5 mg → metformin 1700 mg 
b. Metformin 850 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
c. Metformin 850 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
d. Metformin 1700 mg + glibenclamide 2.5 mg → metformin 2550 mg 
e. Metformin 1700 mg + glibenclamide 5 mg → metformin 2550 mg + glibenclamide 2.5 mg 
f. 
Metformin 1700 mg + glibenclamide 10 mg → metformin 2550 mg + glibenclamide 5 mg 
g. Metformin 2550 mg + glibenclamide 2.5 mg → metformin 2550 mg 
h. Metformin 2550 mg + glibenclamide 5 mg → metformin 2550 mg + glibenclamide 2.5 mg 
i. 
Metformin 2550 mg + glibenclamide 10 mg → metformin 2550 mg + glibenclamide 5 mg 
22. Metformin and glibenclamide, hypoglycemia symptoms, nonadherent, took glibenclamide yesterday → 
same as #16 
23. Metformin and glibenclamide, hypoglycemia symptoms, adherent, did not take glibenclamide yesterday 
→ same as #16 
24. Metformin and glibenclamide, hypoglycemia symptoms, nonadherent, did not take glibenclamide 
yesterday 
a. Metformin all doses + glibenclamide 2.5-5 mg → metformin current dose 
b. Metformin all doses + glibenclamide 10 mg → metformin current dose + glibenclamide 2.5 mg 
25. Metformin and glibenclamide, problems with metformin, hypoglycemia symptoms, adherent, took 
glibenclamide yesterday 
a. Agrees to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → metformin 850 mg 
ii. 
Metformin 850 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 

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b. Refuses to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → MD consult 
ii. 
Metformin 850 mg + glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → glibenclamide 5 mg 
c. Metformin 1700 mg + glibenclamide 2.5 mg → metformin 850 mg  
d. Metformin 1700 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
e. Metformin 1700 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
f. 
Metformin 2550 mg + glibenclamide 2.5 mg → metformin 1700 mg  
g. Metformin 2550 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
h. Metformin 2550 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
26. Metformin and glibenclamide, problems with metformin, hypoglycemia symptoms, nonadherent, took 
glibenclamide yesterday → same as #25 
27. Metformin and glibenclamide, problems with metformin, hypoglycemia symptoms, adherent, did not take 
glibenclamide yesterday 
a. Agrees to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5-5 mg → metformin 850 mg 
ii. 
Metformin 850 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 2.5 mg 
b. Refuses to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5-5 mg → MD consult 
ii. 
Metformin 850 mg + glibenclamide 10 mg → glibenclamide 2.5 mg 
c. Metformin 1700 mg + glibenclamide 2.5-5 mg → metformin 850 mg 
d. Metformin 1700 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 2.5 mg 
e. Metformin 2550 mg + glibenclamide 2.5-5 mg → metformin 1700 mg 
f. 
Metformin 2550 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 2.5 mg 
28. Metformin and glibenclamide, problems with metformin, hypoglycemia or hypoglycemia symptoms, 
nonadherent, did not take glibenclamide yesterday → same as #27 
 
180(200)≤FBG<400 or 300≤PPBG<HI 
1. Metformin without problems, adherent 
a. Metformin 850 mg → metformin 1700 mg 
b. Metformin 1700 mg → metformin 2550 mg 
c. Metformin 2550 mg → metformin 2550 mg + glibenclamide 2.5 mg 
2. Metformin without problems, nonadherent → continue current doses 
3. Metformin with problems, adherent 
a. Metformin 850 mg, willing to continue → metformin 850 mg + glibenclamide 2.5 mg 
b. Metformin 850 mg, not willing to continue → glibenclamide 2.5 mg 
c. Metformin 1700 mg → metformin 850 mg + glibenclamide 2.5 mg 
d. Metformin 2550 mg → metformin 1700 mg + glibenclamide 2.5 mg 
4. Metformin with problems, nonadherent → same as #3 
5. Glibenclamide without problems, no previous problems with metformin, took yesterday 
a. Glibenclamide 2.5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
b. Glibenclamide 5 mg → metformin 1700 mg + glibenclamide 5 mg 
c. Glibenclamide 10 mg → metformin 1700 mg + glibenclamide 10 mg 
6. Glibenclamide without problems, no previous problems with metformin, did not take yesterday 
a. Glibenclamide 2.5 mg → metformin 1700 mg 
b. Glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
c. Glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 

Diabetes Treatment in Rural Guatemala 
 
Jim Svenson 
 
73 
Version #: 1.0 
7. Glibenclamide without problems, previous problems with metformin, took yesterday 
a. Agrees to take metformin → metformin 850 mg + current glibenclamide dose 
b. Refuses to take metformin 
i. 
Glibenclamide 2.5 mg → glibenclamide 5 mg 
ii. 
Glibenclamide 5 mg → glibenclamide 10 mg 
iii. 
Glibenclamide 10 mg → glibenclamide 10 mg 
8. Glibenclamide without problems, previous problems with metformin, did not take yesterday → same as #7 
9. Glibenclamide with hypoglycemia symptoms, no previous problems with metformin, took yesterday 
a. Glibenclamide 2.5 mg → metformin 1700 mg 
b. Glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
c. Glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
10. Glibenclamide with hypoglycemia or hypoglycemia symptoms, no previous problems with metformin, did 
not take yesterday → same as #9 
11. Glibenclamide with hypoglycemia symptoms, previous problems with metformin, took yesterday 
a. Agrees to take metformin 
i. 
Glibenclamide 2.5 mg → metformin 850 mg 
ii. 
Glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
iii. 
Glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
b. Refuses to take metformin 
i. 
Glibenclamide 2.5 mg → MD consult 
ii. 
Glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Glibenclamide 10 mg → glibenclamide 5 mg 
12. Glibenclamide with hypoglycemia symptoms, previous problems with metformin, did not take yesterday → 
same as #11 
13. Metformin and glibenclamide without problems, adherent, took glibenclamide yesterday 
a. Metformin 850 mg + glibenclamide any dose → metformin 1700 mg + glibenclamide current dose 
b. Metformin 1700 mg + glibenclamide any dose → metformin 2550 mg + glibenclamide current 
dose 
c. Metformin 2550 mg + glibenclamide 2.5 mg → metformin 2550 mg + glibenclamide 5 mg 
d. Metformin 2550 mg + glibenclamide 5-10 mg → metformin 2550 mg + glibenclamide 10 mg 
14. Metformin and glibenclamide without problems, nonadherent, took glibenclamide yesterday → continue 
current doses 
15. Metformin and glibenclamide without problems, adherent, did not take glibenclamide yesterday → 
continue current doses 
16. Metformin and glibenclamide without problems, nonadherent, did not take glibenclamide yesterday → 
continue current doses 
17. Metformin and glibenclamide, problems with metformin, adherent, took glibenclamide yesterday 
a. Agrees to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → metformin 850 mg + glibenclamide 5 mg 
ii. 
Metformin 850 mg + glibenclamide 5-10 mg → metformin 850 mg + glibenclamide 10 mg 
b. Refuses to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → glibenclamide 5 mg 
ii. 
Metformin 850 mg + glibenclamide 5 mg → glibenclamide 10 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → glibenclamide 10 mg, MD consult 
c. Metformin 1700 mg + glibenclamide 2.5 mg → metformin 850 mg + glibenclamide 5 mg 
d. Metformin 1700 mg + glibenclamide 5-10 mg → metformin 850 mg + glibenclamide 10 mg 
e. Metformin 2550 mg + glibenclamide 2.5 mg → metformin 1700 mg + glibenclamide 5 mg 

Diabetes Treatment in Rural Guatemala 
 
Jim Svenson 
 
74 
Version #: 1.0 
f. 
Metformin 2550 mg + glibenclamide 5-10 mg → metformin 1700 mg + glibenclamide 10 mg 
18. Metformin and glibenclamide, problems with metformin, nonadherent, took glibenclamide yesterday 
a. Metformin 850 mg + glibenclamide any dose, agrees to take metformin →metformin 850 mg + 
current glibenclamide dose 
b. Metformin 850 mg + glibenclamide any dose, refuses to take metformin → current glibenclamide 
dose 
c. Metformin 1700 mg + glibenclamide any dose → metformin 850 mg + current glibenclamide dose 
d. Metformin 2550 mg + glibenclamide any dose → metformin 1700 mg + current glibenclamide 
dose 
19. Metformin and glibenclamide, problems with metformin, adherent, did not take glibenclamide yesterday → 
same as #18 
20. Metformin and glibenclamide, problems with metformin, nonadherent, did not take glibenclamide 
yesterday → same as #18 
21. Metformin and glibenclamide, hypoglycemia symptoms, adherent, took glibenclamide yesterday 
a. Metformin 850 mg + glibenclamide 2.5 mg → metformin 1700 mg 
b. Metformin 850 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
c. Metformin 850 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
d. Metformin 1700 mg + glibenclamide 2.5 mg → metformin 2550 mg 
e. Metformin 1700 mg + glibenclamide 5 mg → metformin 2550 mg + glibenclamide 2.5 mg 
f. 
Metformin 1700 mg + glibenclamide 10 mg → metformin 2550 mg + glibenclamide 5 mg 
g. Metformin 2550 mg + glibenclamide 2.5 mg → metformin 2550 mg 
h. Metformin 2550 mg + glibenclamide 5 mg → metformin 2550 mg + glibenclamide 2.5 mg 
i. 
Metformin 2550 mg + glibenclamide 10 mg → metformin 2550 mg + glibenclamide 5 mg 
22. Metformin and glibenclamide, hypoglycemia symptoms, nonadherent, took glibenclamide yesterday 
a. Metformin 850 mg + glibenclamide 2.5 mg → metformin 1700 mg 
b. Metformin 850 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
c. Metformin 850 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
d. Metformin 1700 mg + glibenclamide 2.5 mg → metformin 1700 mg 
e. Metformin 1700 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
f. 
Metformin 1700 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
g. Metformin 2550 mg + glibenclamide 2.5 mg → metformin 2550 mg 
h. Metformin 2550 mg + glibenclamide 5 mg → metformin 2550 mg + glibenclamide 2.5 mg 
i. 
Metformin 2550 mg + glibenclamide 10 mg → metformin 2550 mg + glibenclamide 5 mg 
23. Metformin and glibenclamide, hypoglycemia symptoms, adherent, did not take glibenclamide yesterday 
→ same as #22 
24. Metformin and glibenclamide, hypoglycemia symptoms, nonadherent, did not take glibenclamide 
yesterday → same as #22 
25. Metformin and glibenclamide, problems with metformin, hypoglycemia symptoms, adherent, took 
glibenclamide yesterday 
a. Agrees to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → metformin 850 mg 
ii. 
Metformin 850 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
b. Refuses to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → need MD consult to determine meds 
ii. 
Metformin 850 mg + glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → glibenclamide 5 mg 

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Diabetes Treatment in Rural Guatemala 
 
Jim Svenson 
 
76 
Version #: 1.0 
 
5≤ A1c <6 
1. Metformin without problems, adherent 
a. Metformin 850 mg → metformin 850 mg 
b. Metformin 1700 mg → metformin 1700 mg 
c. Metformin 2550 mg → metformin 1700 mg 
2. Metformin without problems, nonadherent → stop medications, recheck A1c in 3 months 
3. Metformin with problems, adherent 
a. Metformin 850 mg, refuses to take metformin → stop medications, recheck A1c in 3 months 
b. Metformin 850 mg, agrees to take metformin → metformin 850 mg 
c. Metformin 1700 mg → metformin 850 mg 
d. Metformin 2550 mg → metformin 1700 mg 
4. Metformin with problems, nonadherent → stop medications, recheck A1c in 3 months 
5. Glibenclamide without problems, no previous problems with metformin, adherent 
a. All doses → metformin 1700 mg 
6. Glibenclamide without problems, no previous problems with metformin, nonadherent → stop medications, 
recheck A1c in 3 months 
7. Glibenclamide without problems, previous problems with metformin, adherent 
a. All doses, agrees to take metformin → metformin 850 mg 
b. All doses, refuses to take metformin → stop medications, recheck A1c in 3 months 
8. Glibenclamide without problems, previous problems with metformin, nonadherent → stop medications, 
recheck A1c in 3 months 
9. Glibenclamide with hypoglycemia or hypoglycemia symptoms, no previous problems with metformin, 
adherent → same as #5 
10. Glibenclamide with hypoglycemia or hypoglycemia symptoms, no previous problems with metformin, 
nonadherent → stop medications, recheck A1c in 3 months 
11. Glibenclamide with hypoglycemia or hypoglycemia symptoms, previous problems with metformin, 
adherent → same as #7 
12. Glibenclamide with hypoglycemia or hypoglycemia symptoms, previous problems with metformin, 
nonadherent → stop medications, recheck A1c in 3 months 
13. Metformin and glibenclamide without problems, adherent 
a. Metformin 850 mg + glibenclamide 2.5-5 mg → metformin 850 mg 
b. Metformin 850 mg + glibenclamide 10 mg → metformin 1700 mg 
c. Metformin 1700-2550 mg + glibenclamide 2.5-5 mg → metformin 1700 mg 
d. Metformin 1700-2550 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 2.5 mg 
14. Metformin and glibenclamide without problems, nonadherent 
a. Metformin 850 mg + glibenclamide any dose → metformin 850 mg 
b. Metformin 1700-2550 mg + glibenclamide any dose → metformin 1700 mg 
15. Metformin and glibenclamide, problems with metformin, adherent 
a. Agrees to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5-5 mg → metformin 850 mg 
ii. 
Metformin 850 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 2.5 mg 
b. Refuses to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → stop medications, recheck A1c in 3 months 
ii. 
Metformin 850 mg + glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → glibenclamide 5 mg 
c. Metformin 1700 mg + glibenclamide 2.5-5 mg → metformin 850 mg 

Diabetes Treatment in Rural Guatemala 
 
Jim Svenson 
 
77 
Version #: 1.0 
d. Metformin 1700 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 2.5 mg 
e. Metformin 2550 mg + glibenclamide 2.5-5 mg → metformin 1700 mg 
f. 
Metformin 2550 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 2.5 mg 
16. Metformin and glibenclamide, problems with metformin, nonadherent 
a. Metformin 850 mg + glibenclamide any dose, agrees to take metformin → metformin 850 mg  
b. Metformin 850 mg + glibenclamide any dose, refuses to take metformin → stop medications, 
recheck A1c in 3 months 
c. Metformin 1700 mg + glibenclamide any dose → metformin 850 mg 
d. Metformin 2550 mg + glibenclamide any dose → metformin 1700 mg 
17. Metformin and glibenclamide, hypoglycemia or hypoglycemia symptoms, adherent 
a. Metformin 850 mg + glibenclamide 2.5-5 mg → metformin 850 mg  
b. Metformin 850 mg + glibenclamide 10 mg → metformin 1700 mg  
c. Metformin 1700-2550 mg + glibenclamide any dose → metformin 1700 mg 
18. Metformin and glibenclamide, hypoglycemia or hypoglycemia symptoms, nonadherent → same as #14 
19. Metformin and glibenclamide, problems with metformin, hypoglycemia or hypoglycemia symptoms, 
adherent 
a. Metformin 850 mg + glibenclamide any dose, agrees to take metformin → metformin 850 mg 
b. Metformin 850 mg + glibenclamide any dose, refuses to take metformin → stop medications, 
recheck A1c in 3 months 
c. Metformin 1700 mg + glibenclamide any dose → metformin 850 mg 
d. Metformin 2550 mg + glibenclamide any dose → metformin 1700 mg 
20. Metformin and glibenclamide, problems with metformin, hypoglycemia or hypoglycemia symptoms, 
nonadherent → same as #16 
 
6≤ A1c ≤Tx goal 
1. Metformin without problems, adherent 
a. Metformin 850 mg → metformin 850 mg 
b. Metformin 1700 mg → metformin 1700 mg 
c. Metformin 2550 mg → metformin 2550 mg 
2. Metformin without problems, nonadherent 
a. Metformin 850 mg → metformin 850 mg 
b. Metformin 1700-2550 mg → metformin 1700 mg 
3. Metformin with problems, adherent 
a. Metformin 850 mg, agrees to take metformin → metformin 850 mg 
b. Metformin 850 mg, refuses to take metformin → glibenclamide 2.5 mg 
c. Metformin 1700 mg → metformin 850 mg 
d. Metformin 2550 mg → metformin 1700 mg 
4. Metformin with problems, nonadherent → same as #3 
5. Glibenclamide without problems, no previous problems with metformin, adherent 
a. All doses → metformin 1700 mg 
6. Glibenclamide without problems, no previous problems with metformin, nonadherent → same as #5 
7. Glibenclamide without problems, previous problems with metformin, adherent 
a. Willing to take metformin  
i. 
Glibenclamide 2.5 mg → metformin 850 mg 
ii. 
Glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
iii. 
Glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
b. Refuses to take metformin → current dose of glibenclamide 

Diabetes Treatment in Rural Guatemala 
 
Jim Svenson 
 
78 
Version #: 1.0 
8. Glibenclamide without problems, previous problems with metformin, nonadherent 
a. Willing to take metformin  
i. 
Glibenclamide 2.5 mg → metformin 850 mg 
ii. 
Glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
iii. 
Glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
b. Refuses to take metformin 
i. 
Glibenclamide 2.5 mg → stop medications, recheck A1c in last 3 months 
ii. 
Glibenclamide 5 mg → glibenclamide 2.5 mg  
iii. 
Glibenclamide 10 mg → glibenclamide 5 mg 
9. Glibenclamide with hypoglycemia or hypoglycemia symptoms, no previous problems with metformin, 
adherent → same as #5 
10. Glibenclamide with hypoglycemia or hypoglycemia symptoms, no previous problems with metformin, 
nonadherent → same as #5 
11. Glibenclamide with hypoglycemia or hypoglycemia symptoms, previous problems with metformin, 
adherent 
a. Agrees to take metformin 
i. 
Glibenclamide 2.5-5 mg → metformin 850 mg 
ii. 
Glibenclamide 10 mg → metformin 850 mg + glibenclamide 2.5 mg 
b. Refuses to take metformin 
i. 
Glibenclamide 2.5 mg → stop medications, recheck A1c in 3 months 
ii. 
Glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Glibenclamide 10 mg → glibenclamide 5 mg 
12. Glibenclamide with hypoglycemia or hypoglycemia symptoms, previous problems with metformin, 
nonadherent → same as #11 
13. Metformin and glibenclamide without problems, adherent → continue current doses 
14. Metformin and glibenclamide without problems, nonadherent 
a. Metformin any dose + glibenclamide 2.5 mg → metformin current dose 
b. Metformin any dose + glibenclamide 5 mg → metformin current dose + glibenclamide 2.5 mg 
c. Metformin any dose + glibenclamide 10 mg → metformin current dose + glibenclamide 5 mg 
15. Metformin and glibenclamide, problems with metformin, adherent 
a. Metformin 850 mg + glibenclamide any dose, agrees to take metformin →metformin 850 mg + 
current glibenclamide dose 
b. Metformin 850 mg + glibenclamide any dose, refuses to take metformin → current glibenclamide 
dose 
c. Metformin 1700 mg + glibenclamide any dose → metformin 850 mg + current glibenclamide dose 
d. Metformin 2550 mg + glibenclamide any dose → metformin 1700 mg + current glibenclamide 
dose 
16. Metformin and glibenclamide, problems with metformin, nonadherent 
a. Agrees to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → metformin 850 mg 
ii. 
Metformin 850 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → metformin 850 mg+ glibenclamide 5 mg 
b. Refuses to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → stop medications, recheck A1c in 3 months 
ii. 
Metformin 850 mg + glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → glibenclamide 5 mg 
c. Metformin 1700 mg + glibenclamide 2.5 mg → metformin 850 mg 

Diabetes Treatment in Rural Guatemala 
 
Jim Svenson 
 
79 
Version #: 1.0 
d. Metformin 1700 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
e. Metformin 1700 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
f. 
Metformin 2550 mg + glibenclamide 2.5 mg → metformin 1700 mg 
g. Metformin 2550 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
h. Metformin 2550 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
17. Metformin and glibenclamide, hypoglycemia or hypoglycemia symptoms, adherent 
a. Metformin any dose + glibenclamide 2.5 mg → metformin current dose 
b. Metformin any dose + glibenclamide 5 mg → metformin current dose + glibenclamide 2.5 mg 
c. Metformin any dose + glibenclamide 10 mg → metformin current dose + glibenclamide 5 mg 
18. Metformin and glibenclamide, hypoglycemia or hypoglycemia symptoms, nonadherent → same as #17 
19. Metformin and glibenclamide, problems with metformin, hypoglycemia or hypoglycemia symptoms, 
adherent 
a. Agrees to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → metformin 850 mg 
ii. 
Metformin 850 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → metformin 850 mg+ glibenclamide 5 mg 
b. Refuses to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → stop medications, recheck A1c in 3 months 
ii. 
Metformin 850 mg + glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → glibenclamide 5 mg 
c. Metformin 1700 mg + glibenclamide 2.5 mg → metformin 850 mg 
d. Metformin 1700 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
e. Metformin 1700 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
f. 
Metformin 2550 mg + glibenclamide 2.5 mg → metformin 1700 mg 
g. Metformin 2550 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
h. Metformin 2550 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
20. Metformin and glibenclamide, problems with metformin, hypoglycemia or hypoglycemia symptoms, 
nonadherent → same as #19 
 
Tx goal< A1c <9 AND FBG >130(150) OR PPBG >180(200 
1. Metformin without problems, adherent 
a. Metformin 850 mg → metformin 1700  mg 
b. Metformin 1700 mg → metformin 2550 mg 
c. Metformin 2550 mg → metformin 2550 mg + glibenclamide 2.5 mg 
2. Metformin without problems, nonadherent 
a. Metformin 850 mg → metformin 1700 mg  
b. Metformin 1700 mg → metformin 1700 mg 
c. Metformin 2550 mg → metformin 2550 mg 
3. Metformin with problems, adherent 
a. Metformin 850 mg, agrees to take metformin → metformin 850 mg + glibenclamide 2.5 mg 
b. Metformin 850 mg, refuses to take metformin → glibenclamide 2.5 mg 
c. Metformin 1700 mg → metformin 850 mg + glibenclamide 2.5 mg 
d. Metformin 2550 mg → metformin 1700 mg + glibenclamide 2.5 mg 
4. Metformin with problems, nonadherent → same as #3 
5. Glibenclamide without problems, no previous problems with metformin, adherent 
a. Any dose → metformin 1700 mg + glibenclamide current dose 
6. Glibenclamide without problems, no previous problems with metformin, nonadherent 

Diabetes Treatment in Rural Guatemala 
 
Jim Svenson 
 
80 
Version #: 1.0 
a. All doses → metformin 1700 mg 
7. Glibenclamide without problems, previous problems with metformin, adherent 
a. Glibenclamide any dose, agrees to take metformin → metformin 850 mg + current glibenclamide 
dose 
b. Refuses to take metformin 
i. 
Glibenclamide 2.5 mg → glibenclamide 5 mg 
ii. 
Glibenclamide 5 mg → glibenclamide 10 mg 
iii. 
Glibenclamide 10 mg → glibenclamide 10 mg 
8. Glibenclamide without problems, previous problems with metformin, nonadherent 
a. Willing to take metformin  
i. 
Glibenclamide 2.5 mg → metformin 850 mg  
ii. 
Glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
iii. 
Glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
b. Refuses to take metformin → continue current glibenclamide dose 
9. Glibenclamide with hypoglycemia or hypoglycemia symptoms, no previous problems with metformin, 
adherent 
a. Glibenclamide 2.5-5 mg → metformin 1700 mg 
b. Glibenclamide 10 mg → metformin 1700 mg + glibenclamide 2.5 mg 
10. Glibenclamide with hypoglycemia or hypoglycemia symptoms, no previous problems with metformin, 
nonadherent → same as #9 
11. Glibenclamide with hypoglycemia or hypoglycemia symptoms, previous problems with metformin, 
adherent 
a. Agrees to take metformin 
i. 
Glibenclamide 2.5 mg → metformin 850 mg 
ii. 
Glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
iii. 
Glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
b. Refuses to take metformin 
i. 
Glibenclamide 2.5 mg → MD consult 
ii. 
Glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Glibenclamide 10 mg → glibenclamide 5 mg 
12. Glibenclamide with hypoglycemia or hypoglycemia symptoms, previous problems with metformin, 
nonadherent → same as #11 
13. Metformin and glibenclamide without problems, adherent 
a. Metformin 850 mg + glibenclamide any dose → metformin 1700 mg + current glibenclamide dose 
b. Metformin 1700 mg + glibenclamide any dose → metformin 2550 mg + glibenclamide current 
dose 
c. Metformin 2550 mg + glibenclamide 2.5 mg → metformin 2550 mg + glibenclamide 5 mg 
d. Metformin 2550 mg + glibenclamide 5 mg → metformin 2550 mg + glibenclamide 10 mg 
e. Metformin 2550 mg + glibenclamide 10 mg → metformin 2550 mg + glibenclamide 10 mg 
14. Metformin and glibenclamide without problems, nonadherent → continue current doses 
15. Metformin and glibenclamide, problems with metformin, adherent 
a. Agrees to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → metformin 850 mg + glibenclamide 5 mg 
ii. 
Metformin 850 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 10 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 10 mg 
b. Refuses to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → glibenclamide 5 mg 

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Jim Svenson 
 
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ii. 
Metformin 850 mg + glibenclamide 5 mg → glibenclamide 10 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → glibenclamide 10 mg 
c. Metformin 1700 mg + glibenclamide 2.5 mg → metformin 850 mg + glibenclamide 5 mg 
d. Metformin 1700 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 10 mg 
e. Metformin 1700 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 10 mg 
f. 
Metformin 2550 mg + glibenclamide 2.5 mg → metformin 1700 mg + glibenclamide 5 mg 
g. Metformin 2550 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 10 mg 
h. Metformin 2550 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 10 mg 
16. Metformin and glibenclamide, problems with metformin, nonadherent 
a. Metformin 850 mg + glibenclamide any dose, agrees to take metformin → metformin 850 mg + 
current glibenclamide dose 
b. Metformin 850 mg + glibenclamide any dose, refuses to take metformin → current glibenclamide 
dose 
c. Metformin 1700 mg + glibenclamide any dose → metformin 850 mg + current glibenclamide dose 
d. Metformin 2550 mg + glibenclamide any dose → metformin 1700 mg + current glibenclamide 
dose 
17. Metformin and glibenclamide, hypoglycemia or hypoglycemia symptoms, adherent 
a. Metformin 850 mg + glibenclamide 2.5 mg → metformin 1700 mg 
b. Metformin 850 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
c. Metformin 850 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
d. Metformin 1700 mg + glibenclamide 2.5 mg → metformin 2550 mg 
e. Metformin 1700 mg + glibenclamide 5 mg → metformin 2550 mg + glibenclamide 2.5 mg 
f. 
Metformin 1700 mg + glibenclamide 10 mg → metformin 2550 mg + glibenclamide 5 mg 
g. Metformin 2550 mg + glibenclamide 2.5 mg → metformin 2550 mg 
h. Metformin 2550 mg + glibenclamide 5 mg → metformin 2550 mg + glibenclamide 2.5 mg 
i. 
Metformin 2550 mg + glibenclamide 10 mg → metformin 2550 mg + glibenclamide 5 mg 
18. Metformin and glibenclamide, hypoglycemia or hypoglycemia symptoms, nonadherent → same as #17 
19. Metformin and glibenclamide, problems with metformin, hypoglycemia or hypoglycemia symptoms, 
adherent 
a. Agrees to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → metformin 850 mg 
ii. 
Metformin 850 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
b. Refuses to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → MD consult 
ii. 
Metformin 850 mg + glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → glibenclamide 5 mg 
c. Metformin 1700 mg + glibenclamide 2.5 mg → metformin 850 mg 
d. Metformin 1700 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
e. Metformin 1700 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
f. 
Metformin 2550 mg + glibenclamide 2.5 mg → metformin 1700 mg 
g. Metformin 2550 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
h. Metformin 2550 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
20. Metformin and glibenclamide, problems with metformin, hypoglycemia or hypoglycemia symptoms, 
nonadherent → same as #19 
 

Diabetes Treatment in Rural Guatemala 
 
Jim Svenson 
 
82 
Version #: 1.0 
Tx goal< A1c <9 AND [FBG ≤130(150) OR PPBG ≤180(200)] → Use dosing recommendations for 6≤ A1c 
≤Tx goal 
 
9≤ A1c ≤14 AND FBG >130(150) OR PPBG >180(200) 
1. Metformin without problems, adherent 
a. Metformin 850 mg → metformin 1700 mg + glibenclamide 2.5 mg 
b. Metformin 1700 mg → metformin 1700 mg + glibenclamide 2.5 mg  
c. Metformin 2550 mg → metformin 2550 mg + glibenclamide 2.5 mg 
2. Metformin without problems, nonadherent 
a. Metformin 850 mg → metformin 1700 mg 
b. Metformin 1700 mg → metformin 1700 mg 
c. Metformin 2550 mg → metformin 2550 mg 
3. Metformin with problems, adherent 
a. Metformin 850 mg, agrees to take metformin → metformin 850 mg + glibenclamide 2.5 mg 
b. Metformin 850 mg, refuses to take metformin → glibenclamide 2.5 mg 
c. Metformin 1700 mg → metformin 850 mg + glibenclamide 2.5 mg 
d. Metformin 2550 mg → metformin 1700 mg + glibenclamide 2.5 mg 
4. Metformin with problems, nonadherent → same as #3 
5. Glibenclamide without problems, no previous problems with metformin, adherent 
a. All doses → metformin 1700 mg +glibenclamide current dose 
6. Glibenclamide without problems, no previous problems with metformin, nonadherent 
a. All doses → metformin 1700 mg + glibenclamide 2.5 mg 
7. Glibenclamide without problems, previous problems with metformin, adherent 
a. Agrees to take metformin → metformin 850 mg + glibenclamide current dose 
b. Refuses to take metformin 
i. 
Glibenclamide 2.5 mg → glibenclamide 5 mg 
ii. 
Glibenclamide 5 mg → glibenclamide 10 mg 
iii. 
Glibenclamide 10 mg → glibenclamide 10 mg 
8. Glibenclamide without problems, previous problems with metformin, nonadherent 
a. Agrees to take metformin  
i. 
Glibenclamide 2.5-5 mg → metformin 850 mg + glibenclamide 2.5 mg 
ii. 
Glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
b. Refuses to take metformin → continue current glibenclamide dose 
9. Glibenclamide with hypoglycemia or hypoglycemia symptoms, no previous problems with metformin, 
adherent 
a. Glibenclamide 2.5 mg → metformin 1700 mg 
b. Glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg  
c. Glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
10. Glibenclamide with hypoglycemia or hypoglycemia symptoms, no previous problems with metformin, 
nonadherent → same as #9 
11. Glibenclamide with hypoglycemia or hypoglycemia symptoms, previous problems with metformin, 
adherent 
a. Agrees to take metformin 
i. 
Glibenclamide 2.5 mg → metformin 850 mg 
ii. 
Glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
iii. 
Glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
b. Refuses to take metformin 

Diabetes Treatment in Rural Guatemala 
 
Jim Svenson 
 
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Version #: 1.0 
i. 
Glibenclamide 2.5 mg → MD consult 
ii. 
Glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Glibenclamide 10 mg → glibenclamide 5 mg 
12. Glibenclamide with hypoglycemia or hypoglycemia symptoms, previous problems with metformin, 
nonadherent → same as #11 
13. Metformin and glibenclamide without problems, adherent 
a. Metformin 850 mg + glibenclamide any dose → metformin 1700 mg + current glibenclamide dose 
b. Metformin 1700 mg + glibenclamide any dose → metformin 2550 mg + glibenclamide current 
dose 
c. Metformin 2550 mg + glibenclamide 2.5 mg → metformin 2550 mg + glibenclamide 5 mg 
d. Metformin 2550 mg + glibenclamide 5 mg → metformin 2550 mg + glibenclamide 10 mg 
e. Metformin 2550 mg + glibenclamide 10 mg → metformin 2550 mg + glibenclamide 10 mg 
14. Metformin and glibenclamide without problems, nonadherent → continue current doses 
15. Metformin and glibenclamide, problems with metformin, adherent 
a. Agrees to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → metformin 850 mg + glibenclamide 5 mg 
ii. 
Metformin 850 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 10 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 10 mg 
b. Refuses to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → glibenclamide 5 mg 
ii. 
Metformin 850 mg + glibenclamide 5 mg → glibenclamide 10 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → glibenclamide 10, mg 
c. Metformin 1700 mg + glibenclamide 2.5 mg → metformin 850 mg + glibenclamide 5 mg 
d. Metformin 1700 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 10 mg 
e. Metformin 1700 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 10 
f. 
Metformin 2550 mg + glibenclamide 2.5 mg → metformin 1700 mg + glibenclamide 5 mg 
g. Metformin 2550 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 10 mg 
h. Metformin 2550 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 10 mg 
16. Metformin and glibenclamide, problems with metformin, nonadherent 
a. Metformin 850 mg + glibenclamide any dose, agrees to take metformin → metformin 850 mg + 
current glibenclamide dose 
b. Metformin 850 mg + glibenclamide any dose, refuses to take metformin → current glibenclamide 
dose 
c. Metformin 1700 mg + glibenclamide any dose → metformin 850 mg + current glibenclamide dose 
d. Metformin 2550 mg + glibenclamide any dose → metformin 1700 mg + current glibenclamide 
dose 
17. Metformin and glibenclamide, hypoglycemia or hypoglycemia symptoms, adherent 
a. Metformin 850 mg + glibenclamide 2.5 mg → metformin 1700 mg 
b. Metformin 850 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
c. Metformin 850 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
d. Metformin 1700 mg + glibenclamide 2.5 mg → metformin 2550 mg 
e. Metformin 1700 mg + glibenclamide 5 mg → metformin 2550 mg + glibenclamide 2.5 mg 
f. 
Metformin 1700 mg + glibenclamide 10 mg → metformin 2550 mg + glibenclamide 5 mg 
g. Metformin 2550 mg + glibenclamide 2.5 mg → metformin 2550 mg 
h. Metformin 2550 mg + glibenclamide 5 mg → metformin 2550 mg + glibenclamide 2.5 mg 
i. 
Metformin 2550 mg + glibenclamide 10 mg → metformin 2550 mg + glibenclamide 5 mg 
18. Metformin and glibenclamide, hypoglycemia or hypoglycemia symptoms, nonadherent → same as #17 

Diabetes Treatment in Rural Guatemala 
 
Jim Svenson 
 
84 
Version #: 1.0 
19. Metformin and glibenclamide, problems with metformin, hypoglycemia or hypoglycemia symptoms, 
adherent 
a. Agrees to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → metformin 850 mg 
ii. 
Metformin 850 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
b. Refuses to take metformin 
i. 
Metformin 850 mg + glibenclamide 2.5 mg → MD consult 
ii. 
Metformin 850 mg + glibenclamide 5 mg → glibenclamide 2.5 mg 
iii. 
Metformin 850 mg + glibenclamide 10 mg → glibenclamide 5 mg 
c. Metformin 1700 mg + glibenclamide 2.5 mg → metformin 850 mg 
d. Metformin 1700 mg + glibenclamide 5 mg → metformin 850 mg + glibenclamide 2.5 mg 
e. Metformin 1700 mg + glibenclamide 10 mg → metformin 850 mg + glibenclamide 5 mg 
f. 
Metformin 2550 mg + glibenclamide 2.5 mg → metformin 1700 mg 
g. Metformin 2550 mg + glibenclamide 5 mg → metformin 1700 mg + glibenclamide 2.5 mg 
h. Metformin 2550 mg + glibenclamide 10 mg → metformin 1700 mg + glibenclamide 5 mg 
20. Metformin and glibenclamide, problems with metformin, hypoglycemia or hypoglycemia symptoms, 
nonadherent → same as #19 
 
9≤ A1c ≤14 AND [FBG ≤130(150) OR PPBG ≤180(200)] → Use dosing recommendations for Tx goal< A1c 
<9 
 
A1c >14 
● 
Coordinator/MD consult for all cases 
 
Appendix 12 - Blood Pressure Protocol 
 

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