Clinical trial NCT00775684
Conditions: Pre-diabetes Type 2 Diabetes
Keywords: Exenatide Sitagliptin Glimepiride Glucagon-Like Peptide-1 Impaired Fasting Glucose Type 2 Diabetes Beta-cell Function Beta-cell Secretory Capacity Glucose-potentiated arginine
Sponsor: University of Pennsylvania
Start date: 2008-10-01; Completion date: 2012-11-01
Enrollment: 47 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

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.

Arms: arm 1: Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects arm 2: Sitagliptin (Januvia®)-100 mg by mouth every morning arm 3: 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
Interventions: intervention 1: Exenatide intervention 2: Sitagliptin intervention 3: Glimepiride
Intervention descriptions: intervention 1: Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects intervention 2: Sitagliptin (Januvia®)100 mg by mouth every morning intervention 3: 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

Protocol documents: