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

This study has been completed.

Sponsor:

Collaborator:

Pennsylvania Department of Health

Information provided by (Responsible Party):

University of Pennsylvania

ClinicalTrials.gov Identifier:

NCT00775684

First received: October 17, 2008

Last updated: January 31, 2013

Last verified: January 2013

History of Changes

Tracking Information

First Received Date ^ICMJE

October 17, 2008

Last Updated Date

January 31, 2013

Start Date ^ICMJE

October 2008

Primary Completion Date

November 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Effect on functional beta-cell mass as determined by change in ß-cell secretory capacity [ Time Frame: 6 months ]

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

Complete list of historical versions of study NCT00775684 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

Change in acute insulin response to arginine [ Time Frame: 6 months ]
Change in glucose-potentiation slope [ Time Frame: 6 months ]
Change in insulin sensitivity [ Time Frame: 6 months ]
Change in disposition index [ Time Frame: 6 months ]
Change in PG 50 (the plasma glucose level at which half-maximal insulin secretion is achieved during the glucose-potentiated arginine test) [ Time Frame: 6 months ]

Original Secondary Outcome Measures ^ICMJE

Same as current

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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

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 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 Type ^ICMJE

Interventional

Study Phase

Not Provided

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment

Condition ^ICMJE

Pre-diabetes
Type 2 Diabetes

Intervention ^ICMJE

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
Drug: Sitagliptin
Sitagliptin (Januvia®)100 mg by mouth every morning
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

Study Arms

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

Intervention: Drug: Exenatide
Experimental: Sitagliptin
Sitagliptin (Januvia®)—100 mg by mouth every morning

Intervention: Drug: Sitagliptin
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

Intervention: Drug: Glimepiride

Publications *

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Completed

Enrollment ^ICMJE

Completion Date

November 2012

Primary Completion Date

November 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria:

Male and female patients age 18 to 70 years.
Ability to provide written informed consent
Mentally stable and able to comply with the procedures of the study protocol
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)
Stable body weight (+ 5%) for at least 2 weeks
Female Patients: Agree to use adequate contraception if reproductively capable. Adequate contraception includes either a hormonal or barrier method, or surgical sterilization.

Exclusion Criteria:

Diagnosis of type 1 diabetes
Receiving insulin, exenatide (Byetta®), or sitagliptin (Januvia®) treatment or taking > 2 oral anti-diabetogenic agents for the treatment of diabetes
BMI > 44 kg/m2
Allergy to any sulfa-containing compounds
Uncontrolled hypertension (SBP >160 or DBP > 100 mmHg)
Uncontrolled hyperlipidemia (triglycerides > 500 or LDL > 160 mg/dl)
Elevation of liver function tests > 2 times the upper limit of normal
Estimated GFR < 55 ml/min/1.73m2 (46)
Hyperkalemia (serum potassium > 5.5 mmol/L)
Moderate anemia (hemoglobin concentration < 12 g/dl in men and < 11 g/dl in women)
Female patients: pregnant or lactating
Hepatic cirrhosis
Known active alcohol or substance abuse
Active cardiovascular disease
Use of any investigational agent within 6 weeks of the baseline visit
Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial

Sex/Gender

Sexes Eligible for Study:

All

Ages

18 Years to 70 Years (Adult, Senior)

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT00775684

Other Study ID Numbers ^ICMJE

808425

Has Data Monitoring Committee

U.S. FDA-regulated Product

Not Provided

IPD Sharing Statement

Not Provided

Responsible Party

University of Pennsylvania

Study Sponsor ^ICMJE

University of Pennsylvania

Collaborators ^ICMJE

Pennsylvania Department of Health

Investigators ^ICMJE

Principal Investigator:

Michael Rickels, M.D., M.S.

University of Pennsylvania, Division of Endocrinology, Diabetes & Metabolism

PRS Account

University of Pennsylvania

Verification Date

January 2013

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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