Incretins in Impaired Fasting Glucose

• ClinicalTrials.gov Identifier: NCT00364377
• Recruitment Status: Completed
• First Posted: August 15, 2006
• Results First Posted: December 6, 2011
• Last Update Posted: December 6, 2011
• Sponsor: Mayo Clinic
• Information provided by (Responsible Party): Adrian Vella, Mayo Clinic

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Pre-diabetes	Drug: Sitagliptin; Other: Placebo	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: The Role of Incretins in the Pathogenesis of Fasting and Postprandial Glucose Metabolism in People With Impaired Fasting Glucose
• Study Start Date: August 2006
• Actual Primary Completion Date: December 2008
• Actual Study Completion Date: December 2008

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Sitagliptin; People with impaired fasting glucose randomized to treatment with sitagliptin 100 mg once daily.	Drug: Sitagliptin; 100 mg once daily; Other Name: Januvia
Placebo Comparator: Placebo; People with impaired fasting glucose randomized to treatment with placebo once daily.	Other: Placebo; once daily for duration of the study

Outcome Measures

Primary Outcome Measures :

1. Lowering of Fasting Glucose [ Time Frame: 8 weeks ]
   fasting glucose taken as the mean of blood glucose measured at -30, -20, -10 and 0 minutes prior to each inpatient meal study

Eligibility Criteria

• Ages Eligible for Study: 35 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Twenty four participants aged 35 to 70 years with impaired fasting glucose (100mg/dl-125 mg/dl) will be studied.

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.

Contacts and Locations

Locations

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

Investigators

• Principal Investigator: Adrian Vella, M.D.; Mayo Clinic

More Information

Additional Information:

Mayo Clinic Clinical Trials 

Publications of Results:

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.

• Responsible Party: Adrian Vella, Professor of medicine, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT00364377
• Other Study ID Numbers: 06-002673
• First Posted: August 15, 2006
• Results First Posted: December 6, 2011
• Last Update Posted: December 6, 2011
• Last Verified: November 2011

Additional relevant MeSH terms:

Prediabetic State; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Sitagliptin Phosphate; Hypoglycemic Agents; Physiological Effects of Drugs; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dipeptidyl-Peptidase IV Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action