Official Title: “Glimepiride Induced Insulin Secretion Will be Inhibited by Hypoglycemia”

This study will look at two FDA approved medications that improve how the pancreas works in patients with Type 2 Diabetes. In order to understand how these medications work in patients with diabetes we must first measure the normal response in healthy volunteers without diabetes. We will be looking at the body's normal physiological response to low blood sugar and whether this will be modified by these medicationsThe hypothesis would be that glimepiride induced insulin secretion will be inhibited by hypoglycemia.

Study Type: Interventional

Study Design: Other, Randomized, Single Blind (Subject), Factorial Assignment

Study Primary Completion Date: April 2008

In patients with type 2 diabetes, sulfonylurea drugs are a mainstay for effective glucose control. These agents produce their hypoglycemic effects via stimulation of endogenous insulin secretion. Oversecretion of insulin, per se, or a continued relative increase of the hormone even when plasma glucose is normal will result in hypoglycemia. This latter situation commonly occurs if a patient decides to omit, delay, or reduce the size of a meal.

An important defense against hypoglycemia in the above situations is glucose dependent regulation of insulin secretion. In other words, a low ambient glucose concentration could regulate the magnitude of the amount of insulin released in response to a sulfonylurea. Thus during hypoglycemic conditions, the sulfonylurea would result in little or no insulin secretion, whereas its effects during hyperglycemia would be amplified. Glimepiride and glyburide are both second-generation sulfonlyurea drugs used commonly for treatment of type 2 diabetes. This study will compare the two and ask the following question:

Is Glimepiride insulin secretion dependent upon glucose concentration in-vivo?

Intervention(s) in this Clinical Trial

• Drug: Glimepiride
  • Glimepiride (Amaryl) 4 mg oral dose during protocol, given once during each protocol.
• Drug: glyburide
  • Glyburide (Dia-Beta) 10 mg oral dose during protocol, given once during each protocol.
• Other: glucose clamp
  • Hyperinsulinemic euglycemic glucose clamp procedure-120 minutes
• Other: glucose clamp
  • hypoglycemic glucose clamp procedure -120 minutes

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
• Experimental: 2
• Experimental: 3
  • control-euglycemia
• Experimental: 4
  • control-hypoglycemia

Primary Measures

• catecholamines
  • Time Frame: 1 day
    Safety Issue?: No

Inclusion Criteria:

• Healthy male and female subjects aged 30-60
• Body Mass Index 21-30 kg/m2
• All potential volunteers will have routine blood test to screen for hepatic, renal, and hematological abnormalities
• EKG treadmill stress test for volunteers over 40 years of age.
• Female volunteers of childbearing potential will undergo HCG pregnancy test.

Exclusion Criteria:

• Prior or current history of poor health
• Abnormal results following screening tests
• Pregnancy
• History of allergy to sulfonylurea or related drugs

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 30 Years

Maximum Age for this Clinical Trial: 60 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Vanderbilt University

Overall Clinical Trial Officials and Contacts

Stephen N. Davis, MD Principal Investigator Vanderbilt University  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00608179

Study ID Number: IRB #020690

ClinicalTrials.gov Identifier: NCT00608179

Health Authority: United States: Institutional Review Board