Incretins in Impaired Fasting Glucose

NCT ID: NCT00364377

Last Updated: 2011-12-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-08-31
• Study Completion Date: 2008-12-31

Brief Summary

People with high fasting glucose can develop type 2 diabetes with the passage of time. This study is being done to determine the effect of a novel medication in people with this elevated fasting glucose. Sitagliptin is a substance that raises levels of a hormone normally found in the blood. This hormone, called glucagon-like peptide-1 (GLP-1), is normally released by the intestine in response to the presence of food. This hormone acts like a messenger between the intestine and the pancreas to raise insulin levels, and therefore, lower blood sugars. Sitagliptin is effective in people with diabetes, however, this study is being done to determine if Sitagliptin is effective in people with high fasting glucose who do not yet have diabetes.

Detailed Description

Impaired fasting glucose (IFG) confers a high risk of progression to diabetes. Its pathogenesis has been an area of active investigation, with defects in insulin and glucagon secretion as well as insulin action likely to play a role. Several studies have suggested that the prediabetic and diabetic state are associated with alterations in circulating incretin concentrations. More recently, a large study of non-diabetic individuals demonstrated decreased GLP-1 concentrations after a glucose challenge in individuals with prediabetes but concluded that defects in GLP-1 secretion were unrelated to insulin secretion. In impaired glucose tolerance (IGT), defects in incretin-induced insulin secretion coexist with defects in glucose induced insulin secretion.

Worsening degrees of glucose tolerance are associated with decreased insulin secretion for the prevailing insulin action. Moreover early glucagon suppression is impaired in IGT. Since GLP-1 is an insulin secretagogue and suppresses glucagon, it is conceivable that defects in GLP-1 secretion could contribute to the pathogenesis of pre-diabetes. Inhibition of Dipeptidyl Peptidase-4 (DPP-4), an enzyme which rapidly degrades the incretin hormones, has been shown to be a useful therapeutic strategy in type 2 diabetes. DPP-4 inhibitors increase (model-calculated) insulin secretion and decrease glucagon concentrations resulting in a lowering of fasting (and postprandial) glucose concentrations in people with type 2 diabetes. Their effects in people with IFG are less certain. However, DPP-4 inhibitors provide an opportunity to directly examine the contribution of abnormal incretin concentrations to the pathogenesis of IFG, by raising concentrations of endogenous incretin hormones.

The current experiments tested this hypothesis by measuring insulin secretion and action and fasting and postprandial glucose turnover before and after 8 weeks of therapy with a DPP-4 inhibitor.

Conditions

Pre-diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Sitagliptin

People with impaired fasting glucose randomized to treatment with sitagliptin 100 mg once daily.

Group Type: ACTIVE_COMPARATOR

Sitagliptin

Intervention Type: DRUG

100 mg once daily

Placebo

People with impaired fasting glucose randomized to treatment with placebo once daily.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

once daily for duration of the study

Interventions

Sitagliptin

100 mg once daily

Intervention Type: DRUG

Placebo

once daily for duration of the study

Intervention Type: OTHER

Other Intervention Names

Januvia

Eligibility Criteria

Inclusion Criteria

• Males and females between the ages of 35-70.
• Good health as determined by past medical history,physical examination, vital signs, electrocardiogram and laboratory tests at the time of screening.
• Patients on diuretics or thyroid hormone therapy must be on a stable dose (at least 3 months prior to screening) and the maintenance dose may not be adjusted during the study.

Exclusion Criteria

• Individuals with a body mass index less than 19 or greater than 40 kg/m^2, or a total weight > 130 kg, will be excluded from study.
• Subjects less than 35 years will not be studied in order to minimize the possibility of studying subjects with type 1 diabetes.
• No history of a) significant nephropathy, (i.e., plasma creatinine > 1.4 mg/dl in women and 1.5 mg/dl in men, and/or proteinuria); b) clinically significant atherosclerotic vascular disease (e.g., history of heart attack or angina); c) a known systemic illness.
• Pregnant or lactating females.

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Adrian Vella

Professor of medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Adrian Vella, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

References

Bock G, Dalla Man C, Micheletto F, Basu R, Giesler PD, Laugen J, Deacon CF, Holst JJ, Toffolo G, Cobelli C, Rizza RA, Vella A. The effect of DPP-4 inhibition with sitagliptin on incretin secretion and on fasting and postprandial glucose turnover in subjects with impaired fasting glucose. Clin Endocrinol (Oxf). 2010 Aug;73(2):189-96. doi: 10.1111/j.1365-2265.2009.03764.x. Epub 2009 Dec 18.

Reference Type: RESULT

PMID: 20039889 (View on PubMed)

Other Identifiers

06-002673

Identifier Type: -

Identifier Source: org_study_id