Pioglitazone Incretin Study
Incretin hormones are hormones produced by the gut in response to food intake. These hormones help the body to control the metabolism of glucose (sugar). In particular, two incretin hormones (GLP-1 and GIP) cause the pancreas to secrete more insulin in response to high blood glucose levels. This helps the body to metabolize the glucose more effectively, lowering blood sugar levels. GLP-1 and GIP do not work as well in patients with type 2 diabetes (T2DM) as in subjects who do not have diabetes. This study tests whether a medicine called pioglitazone (Actos), which is commonly used to treat T2DM, improves the ability of GIP to increase insulin secretion.
To address this question the investigators will recruit patients with T2DM whose diabetes is controlled with either diet and exercise or with metformin (another medicine commonly used to treat T2DM). Subjects will undergo measurement of body fat by DEXA scanning and a series of studies to characterize their metabolism. These studies include an oral glucose tolerance test (a test sometimes used to diagnose diabetes), a mixed-meal challenge (to measure how much GLP-1 and GIP are produced in response to a meal) and measurement of insulin secretion in response to glucose and GIP given through a vein. The investigators will also obtain small samples of fat (from just under the skin of the belly) using a needle to measure levels of the receptor for GIP. Subjects will then be randomly assigned to 12 weeks of treatment with either pioglitazone or matching placebo (an inactive tablet that does not contain medication). The dose of pioglitazone will be increased during the first 4 weeks to the maximum prescribed dose of 45 mg per day. Subjects will be seen every 2-4 weeks during the treatment phase of the study. After 12 weeks of treatment all studies performed at the beginning of the study will be repeated. The pioglitazone treatment will continue until the end of testing, approximately 4 weeks.
The results of this study may give us information about why glucose control deteriorates in T2DM. This information might also lead to new ways to prevent or treat T2DM.
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
|Official Title:||Effects of Pioglitazone on the Regulation of Insulin Secretion in Patients With Type 2 Diabetes|
- Change in incretin-mediated insulin secretion and receptor regulation of glucose-dependent insulinotropic peptide (GIP) in patients with type 2 diabetes. [ Time Frame: 12 weeks per subject ] [ Designated as safety issue: No ]
- Change in active GIP in response to an oral glucose tolerance test and mixed meal challenge [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Change in active GLP-1 in response to the oral glucose tolerance test and the mixed meal challenge [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Change in glucose response during the oral glucose tolerance test and mixed meal challenge [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Change in insulin secretion during the oral glucose tolerance test and the mixed meal challenge [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Change in the acute insulin response to glucose, insulin sensitivity and the disposition index during the IV glucose tolerance test. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Change in adipocyte GIP receptor mRNA expression levels. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||May 2008|
|Study Completion Date:||November 2010|
|Primary Completion Date:||November 2010 (Final data collection date for primary outcome measure)|
Active Comparator: 1
Starting dose at 15 mg for two weeks, then titrated up to 45 mg in the subsequent 2 weeks.
Other Name: Actos (brand name for pioglitazone)
Placebo Comparator: 2
Please refer to this study by its ClinicalTrials.gov identifier: NCT00656864
|United States, Vermont|
|University of Vermont|
|South Burlington, Vermont, United States, 05403|
|Principal Investigator:||Richard E Pratley, MD||University of Vermont|