Effect of Exenatide, Sitagliptin or Glimepiride on Functional ß -Cell Mass

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT00775684
• Collaborator: Pennsylvania Department of Health (Other)
• Enrollment: 47
• Locations: 3
• Arms: 3
• Duration (Months): 49
• Patients Per Site: 15.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study evaluates exenatide, sitagliptin, and glimepiride for the treatment of high blood sugar in patients with impaired fasting glucose or early type 2 diabetes. The purpose of this study is to determine if exenatide and sitagliptin increase the amount of insulin made by the pancreas compared to glimepiride. It is hypothesized that exenatide or sitagliptin will sustain or increase the amount of insulin made by the pancreas in comparison to glimepiride.

Condition or Disease	Intervention/Treatment	Phase
Pre-diabetes; Type 2 Diabetes	Drug: Exenatide; Drug: Sitagliptin; Drug: Glimepiride	N/A

Detailed Description

The incidence of type 2 diabetes (T2D) has reached epidemic proportions throughout the world. In the United States more than 1.5 million new cases of diabetes were diagnosed in 2005, and the estimated prevalence of the disease was over 20 million. Another 54 million Americans are believed to have impaired fasting glucose, which represents a "pre-diabetic" state at increased risk for progression to overt diabetes. T2D ultimately results from an inadequate mass of functional beta-cells, where insufficient beta-cell compensation for insulin resistance leads to the development of impaired glucose tolerance and eventually diabetes. Autopsy studies have demonstrated a decreased beta-cell mass occurring with fasting glucose > 110 mg/dl, consistent with functional studies that demonstrate decreased beta-cell (insulin) secretory capacity beginning in the range of impaired fasting glucose. Strategies that might preserve or expand functional beta-cell mass in vivo would be expected to reverse the progressive deterioration in blood glucose control seen with diabetes. One such strategy involves the incretin hormone glucagon-like peptide-1 (GLP-1), which is trophic for islet beta-cells, having both pro-proliferative and anti-apoptotic effects. However, it is not known whether increasing GLP-1 effects can preserve or enhance functional beta-cell mass in humans. This proposal will determine the effect of increasing GLP-1 levels on functional beta-cell mass in human subjects with impaired fasting glucose (fasting glucose 110 - 126 mg/dl) or early T2D (fasting glucose 127 - 149 mg/dl) where a critical window exists for reversing further beta-cell deterioration. GLP-1 effects will be promoted by administration of either the GLP-1 analog, exenatide, or by increasing endogenous GLP-1 levels through administration of the oral dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin for a 6-month period. To control for the effect of exenatide and sitagliptin on normalization of blood glucose, subjects will be randomized to receive exenatide, sitagliptin or the sulfonylurea glimepiride, the latter being a first-line anti-diabetogenic agent that will serve as an active comparator.

Study Design

• Study Type: Interventional
• Actual Enrollment: 47 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Controlled Trial Comparing the Effect of Exenatide, Sitagliptin or Glimepiride on Functional ß -Cell Mass in Patients With Impaired Fasting Glucose or Early Type 2 Diabetes
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Exenatide Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects	Drug: Exenatide; Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects; Other Names: Byetta®
Experimental: Sitagliptin Sitagliptin (Januvia®)-100 mg by mouth every morning	Drug: Sitagliptin; Sitagliptin (Januvia®)100 mg by mouth every morning; Other Names: Januvia®
Active Comparator: Glimepiride Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose < 110mg/dl	Drug: Glimepiride; Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose < 110mg/dl; Other Names: Amaryl®

Outcome Measures

Primary Outcome Measures

1. Effect on Functional Beta-cell Mass as Determined by Change in ß-cell Secretory Capacity at 6 Months (μU/ml) [Baseline and 6 months]

   The acute insulin response to arginine (AIRarg) performed during the 340mg/dl glucose clamp allows for estimation of the the beta-cell secretory capacity (AIRmax) or functional beta-cell mass. Changes from baseline to 6 months of AIRmax were compared across groups

2. Effect on Functional Beta-cell Mass as Determined by Change in ß-cell Secretory Capacity at 6 Months (pg/mL) [Baseline and 6 months]

   AGRmin is performed during the 340mg/dl glucose clamp allows for estimation of the minimum alpha-cell glucagon secretion. Changes from baseline to 6 months of AGRmin were compared across groups.

Secondary Outcome Measures

1. Change in Acute Insulin Response to Arginine. (AIRarg) [Baseline and 6 months]

   The changes in B-cell insulin secretion, Acute Insulin Response to arginine (AIRarg) after 6 months were compared to baseline AIRarg for each group. Listed below are AIRarg at baseline and 6 months for each group.

2. Insulin Sensitivity at Baseline and 6 Months [Baseline and 6 months]

   Insulin sensitivity (M/I) was determined by dividing the mean glucose infusion rate required during the 230 mg/dL glucose clamp (M) by the mean prestimulus insulin level (I) between 40 and 45 min of the glucose infusion The mean difference after 6 months in insulin sensitivity (M/I) were compared

3. PG 50 (the Plasma Glucose Level at Which Half-maximal Insulin Secretion is Achieved During the Glucose-potentiated Arginine Test) at Baseline and 6 Months [Baseline and 6 months]

   Between ∼60 and 250 mg/dL, the magnitude of AIRarg is a linear function of the plasma glucose level, so the difference in AIRarg at fasting and 230 mg/dL glucose levels divided by the difference in plasma glucose (ΔAIRarg/ΔPG) gives the glucose-potentiation slope (GPS) (8,24-26). Using the y-intercept (b) from the line created by these two points, the plasma glucose level at which half-maximal insulin secretion is achieved (PG50) is derived from solving the equation 1/2 (AIRmax) = (GPS · PG50) + b, and provides a measure of β-cell sensitivity to glucose The mean difference after 6 months in PG 50 were compared. Listed below are the PG50 values at baseline and 6 months.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male and female patients age 18 to 70 years.

2. Ability to provide written informed consent

3. Mentally stable and able to comply with the procedures of the study protocol

4. Clinical history compatible with impaired fasting glucose or early T2D as defined by a plasma glucose concentration between 110-159 mg/dl following a 12 hour overnight fast performed off any anti-diabetogenic agent for at least 2 weeks (6 weeks for thiazolidinediones)

5. Stable body weight (+ 5%) for at least 2 weeks

6. Female Patients: Agree to use adequate contraception if reproductively capable. Adequate contraception includes either a hormonal or barrier method, or surgical sterilization.

Exclusion Criteria:

1. Diagnosis of type 1 diabetes

2. Receiving insulin, exenatide (Byetta®), or sitagliptin (Januvia®) treatment or taking

2 oral anti-diabetogenic agents for the treatment of diabetes

1. BMI > 44 kg/m2

2. Allergy to any sulfa-containing compounds

3. Uncontrolled hypertension (Systolic Blood Pressure >160 or Diastolic Blood Pressure > 100 mmHg)

4. Uncontrolled hyperlipidemia (triglycerides > 500 or LDL > 160 mg/dl)

5. Elevation of liver function tests > 2 times the upper limit of normal

6. Estimated Glomerular Filtration Rate (GFR) < 55 ml/min/1.73m2 (46)

7. Hyperkalemia (serum potassium > 5.5 mmol/L)

8. Moderate anemia (hemoglobin concentration < 12 g/dl in men and < 11 g/dl in women)

9. Female patients: pregnant or lactating

10. Hepatic cirrhosis

11. Known active alcohol or substance abuse

12. Active cardiovascular disease

13. Use of any investigational agent within 6 weeks of the baseline visit

14. Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical and Translational Research Center, Hospital of University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
2	Rodebaugh Diabetes Center, Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
3	Pennsylvania Hospital	Philadelphia	Pennsylvania	United States	19107

Sponsors and Collaborators

• University of Pennsylvania
• Pennsylvania Department of Health

Investigators

• Principal Investigator: Michael Rickels, M.D., M.S., University of Pennsylvania, Division of Endocrinology, Diabetes & Metabolism

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Michael R. Rickels, M.D., M.S. Faculty Bio
• Rodebaugh Diabetes Center
• Center for Human Phenomic Science (Formerly the Clinical and Translational Research Center)
• Institute for Diabetes, Obesity & Metabolism - Clinical Trials

Publications

• Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes. 2003 Jan;52(1):102-10.
• Godsland IF, Jeffs JAR, Johnston DG. Loss of beta cell function as fasting glucose increases in the non-diabetic range. Diabetologia. 2004 Jul;47(7):1157-1166. doi: 10.1007/s00125-004-1454-z. Epub 2004 Jul 13.
• Kahn SE. Clinical review 135: The importance of beta-cell failure in the development and progression of type 2 diabetes. J Clin Endocrinol Metab. 2001 Sep;86(9):4047-58. Review.
• King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998 Sep;21(9):1414-31.
• National Diabetes Statistics http://diabetes.niddk.nih.gov/dm/pubs/statistics/index.htm 2005. 2-16-2007 Ref Type: Electronic Citation
• Ritzel RA, Butler AE, Rizza RA, Veldhuis JD, Butler PC. Relationship between beta-cell mass and fasting blood glucose concentration in humans. Diabetes Care. 2006 Mar;29(3):717-8.
• U.K. prospective diabetes study 16. Overview of 6 years' therapy of type II diabetes: a progressive disease. U.K. Prospective Diabetes Study Group. Diabetes. 1995 Nov;44(11):1249-58. Erratum in: Diabetes 1996 Nov;45(11):1655.
• Ward WK, Bolgiano DC, McKnight B, Halter JB, Porte D Jr. Diminished B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus. J Clin Invest. 1984 Oct;74(4):1318-28.

• Responsible Party: Michael R. Rickels, MD, MS, Professor of Medicine, University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT00775684
• Other Study ID Numbers: 808425
• First Posted: Oct 20, 2008
• Last Update Posted: Jun 7, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Michael R. Rickels, MD, MS, Professor of Medicine, University of Pennsylvania: Exenatide; Sitagliptin; Glimepiride; Glucagon-Like Peptide-1; Impaired Fasting Glucose; Type 2 Diabetes; Beta-cell Function; Beta-cell Secretory Capacity; Glucose-potentiated arginine
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Prediabetic State; Sitagliptin Phosphate; Exenatide; Glimepiride

Study Results

Participant Flow

Recruitment Details	Recruitment is now closed for this study. All subject follow-up was completed in the spring of 2012. The purpose of the study was to evaluate three medications for the treatment of high blood sugar.

Arm/Group Title	Exenatide	Sitagliptin	Glimepiride
Arm/Group Description	Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects Exenatide: Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects	Sitagliptin (Januvia®)-100 mg by mouth every morning Sitagliptin: Sitagliptin (Januvia®)100 mg by mouth every morning	Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose < 110mg/dl Glimepiride: Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose < 110mg/dl
Period Title: Overall Study
STARTED	17	13	17
COMPLETED	14	12	14
NOT COMPLETED	3	1	3

Baseline Characteristics

Arm/Group Title	Exenatide	Sitagliptin	Glimepiride	Total
Arm/Group Description	Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects Exenatide: Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects	Sitagliptin (Januvia®)-100 mg by mouth every morning Sitagliptin: Sitagliptin (Januvia®)100 mg by mouth every morning	Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose < 110mg/dl Glimepiride: Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose < 110mg/dl	Total of all reporting groups
Overall Participants	17	13	17	47
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	17 100%	13 100%	17 100%	47 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57 (2)	57 (3)	52 (3)	55.3 (2.6)
Sex: Female, Male (Count of Participants)
Female	6 35.3%	4 30.8%	7 41.2%	17 36.2%
Male	11 64.7%	9 69.2%	10 58.8%	30 63.8%
Region of Enrollment (participants) [Number]
United States	17 100%	13 100%	17 100%	47 100%

Outcome Measures

1. Primary Outcome

Title	Effect on Functional Beta-cell Mass as Determined by Change in ß-cell Secretory Capacity at 6 Months (μU/ml)
Description	The acute insulin response to arginine (AIRarg) performed during the 340mg/dl glucose clamp allows for estimation of the the beta-cell secretory capacity (AIRmax) or functional beta-cell mass. Changes from baseline to 6 months of AIRmax were compared across groups
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

We conducted a randomized controlled trial in 40 adult subjects with early Type 2 diabetes (T2D) who received the glucagon-like peptide (GLP-1) analog exenatide, the dipeptidyl peptidase IV inhibitor sitagliptin or the sulfonylurea glimepiride as an active comparator insulin secretagogue for 6 months.

Arm/Group Title	Exenatide	Sitagliptin	Glimepiride
Arm/Group Description	Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects Exenatide: Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects	Sitagliptin (Januvia®)-100 mg by mouth every morning Sitagliptin: Sitagliptin (Januvia®)100 mg by mouth every morning	Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose < 110mg/dl Glimepiride: Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose < 110mg/dl
Measure Participants	14	12	14
Acute Insulin Response (AIRmax)Baseline	214 (60)	149 (20)	133 (19)
Acute Insulin Response (AIRmax) 6 Months	188.5 (34.6)	158.3 (30.3)	202.5 (35.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide, Glimepiride
	Comments	Student t test
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.1
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Glimepiride
	Comments	Repeated measure (baseline and 6 months)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.05
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Change in Acute Insulin Response to Arginine. (AIRarg)
Description	The changes in B-cell insulin secretion, Acute Insulin Response to arginine (AIRarg) after 6 months were compared to baseline AIRarg for each group. Listed below are AIRarg at baseline and 6 months for each group.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AIRarg Exenatide	AIRarg Sitagliptin	AIRarg Glimepiride
Arm/Group Description	Acute insulin response to arginine	Acute insulin response to arginine	Acute insulin response to arginine
Measure Participants	14	12	14
Acute Insulin Response (AIRarg) Baseline	52 (14)	35 (4)	44 (6)
Acute Insulin Response (AIRarg) 6 Months	52 (11)	34 (6)	42 (4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide, Glimepiride
	Comments	Within group changes over 6 months (delta= final - baseline) were compared.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.1
	Comments
	Method	t-test, 1 sided
	Comments

3. Secondary Outcome

Title	Insulin Sensitivity at Baseline and 6 Months
Description	Insulin sensitivity (M/I) was determined by dividing the mean glucose infusion rate required during the 230 mg/dL glucose clamp (M) by the mean prestimulus insulin level (I) between 40 and 45 min of the glucose infusion The mean difference after 6 months in insulin sensitivity (M/I) were compared
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	M/I Exenatide	M/I Sitagliptin	M/I Glimepiride
Arm/Group Description	Change in insulin sensitivity	Change in insulin sensitivity	Change in insulin sensitivity
Measure Participants	14	12	14
M/I Baseline	0.3 (0.1)	0.3 (0.0)	0.3 (0.1)
M/I 6 Months	0.3 (0.1)	0.3 (0.1)	0.3 (0.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide, Sitagliptin, Glimepiride
	Comments	To determine if exenatide or sitagliptin induced significant changes from baseline, the change for each measure (Δ = final - baseline) for each group was compared with the change in the glimepiride group using independent Student t tests
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.1
	Comments
	Method	t-test, 1 sided
	Comments

4. Secondary Outcome

Title	PG 50 (the Plasma Glucose Level at Which Half-maximal Insulin Secretion is Achieved During the Glucose-potentiated Arginine Test) at Baseline and 6 Months
Description	Between ∼60 and 250 mg/dL, the magnitude of AIRarg is a linear function of the plasma glucose level, so the difference in AIRarg at fasting and 230 mg/dL glucose levels divided by the difference in plasma glucose (ΔAIRarg/ΔPG) gives the glucose-potentiation slope (GPS) (8,24-26). Using the y-intercept (b) from the line created by these two points, the plasma glucose level at which half-maximal insulin secretion is achieved (PG50) is derived from solving the equation 1/2 (AIRmax) = (GPS · PG50) + b, and provides a measure of β-cell sensitivity to glucose The mean difference after 6 months in PG 50 were compared. Listed below are the PG50 values at baseline and 6 months.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	P50 Exenatide	P50 Sitagliptin	P50 Glimepiride
Arm/Group Description	Plasma glucose level at which half-maximal insulin secretion is achieved during the glucose-potentiated arginine test	Plasma glucose level at which half-maximal insulin secretion is achieved during the glucose-potentiated arginine test	Plasma glucose level at which half-maximal insulin secretion is achieved during the glucose-potentiated arginine test
Measure Participants	14	12	14
PG50 Baseline	175 (13)	226 (12)	168 (17)
PG50 6 Months	190 (14)	209 (16)	182 (10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide, Sitagliptin, Glimepiride
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.1
	Comments
	Method	t-test, 1 sided
	Comments

5. Primary Outcome

Title	Effect on Functional Beta-cell Mass as Determined by Change in ß-cell Secretory Capacity at 6 Months (pg/mL)
Description	AGRmin is performed during the 340mg/dl glucose clamp allows for estimation of the minimum alpha-cell glucagon secretion. Changes from baseline to 6 months of AGRmin were compared across groups.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

We conducted a randomized controlled trial in 40 adult subjects with early Type 2 diabetes (T2D) who received the glucagon-like peptide (GLP-1) analog exenatide, the dipeptidyl peptidase IV inhibitor sitagliptin or the sulfonylurea glimepiride as an active comparator insulin secretagogue for 6 months.

Arm/Group Title	Exenatide	Sitagliptin	Glimepiride
Arm/Group Description	Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects Exenatide: Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects	Sitagliptin (Januvia®)-100 mg by mouth every morning Sitagliptin: Sitagliptin (Januvia®)100 mg by mouth every morning	Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose < 110mg/dl Glimepiride: Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose < 110mg/dl
Measure Participants	14	12	14
Acute Glucose Response (AGRmin) Baseline	51 (12)	55 (8)	37 (6)
Acute Glucose Response (AGRmin) 6 Months	52 (12)	59 (19)	59 (8)

Adverse Events

Arm/Group Title	Exenatide		Sitagliptin		Glimepiride
Arm/Group Description	Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects Exenatide: Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects		Sitagliptin (Januvia®)-100 mg by mouth every morning Sitagliptin: Sitagliptin (Januvia®)100 mg by mouth every morning		Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose < 110mg/dl Glimepiride: Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose < 110mg/dl
All Cause Mortality
	Exenatide		Sitagliptin		Glimepiride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/13 (0%)		0/17 (0%)
Serious Adverse Events
	Exenatide		Sitagliptin		Glimepiride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/13 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Exenatide		Sitagliptin		Glimepiride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/13 (0%)		0/17 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.