Vildagliptin and the Glucagon Response to Hypoglycemia in Insulin-Treated Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to explore whether the novel therapy of type 2 diabetes, vildagliptin, which inhibits dipeptidyl peptidase-4 (DPP-4), affects glucagon counterregulation during hypoglycemia in insulin-treated patients with type 2 diabetes. Vildagliptin is given, together with the on-going insulin therapy, for one month, whereafter hypoglycemia is induced under standardized conditions, and the glucagon response is determined, and compared to that after a month of placebo treatment.

Detailed Description
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Vildagliptin is an inhibitor of dipeptidyl peptidase-4 (DPP-4) and inhibits glucagon secretion and stimulates insulin secretion. This improves glycemia in subjects with type 2 diabetes with a very low risk for hypoglycemia. If hypoglycemia nevertheless develops, it is important that vildagliptin under such conditions does not inhibit glucagon secretion, since that would aggravate the hypoglycemia. It was indeed previously demonstrated in type 2 diabetes that vildagliptin dos not inhibit glucagon secretion during hypoglycemia. This study explores whether vildagliptin affects glucagon counterregulation during hypoglycemia in insulin-treated patients of type 2 diabetes. Vildagliptin is given, together with the on-going insulin therapy, for one month, whereafter hypoglycemia is induced under standardized conditions, and the glucagon response is determined, and compared to that after a month of placebo treatment. The hypoglycemia is induced bvy a standardized clamp procedure.

Official Title
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Study of the Effect of Vildagliptin on Glucagon Counterregulation Response During Hypoglycemia in Insulin-treated Patients With Type 2 Diabetes

Conditions
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Diabetes

Intervention / Treatment
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* Drug: Vildagliptin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes Insulin treatment Age >18 years HbA1c <=8.5% Exclusion Criteria: Pregnancy Lactation Acute infection Liver disease Treatment with cortisol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vildagliptin<br>Vildagliptin (50 mg BID) given for four weeks | Drug: Vildagliptin<br>* Vildagliptin (50 mg BID) given for four weeks<br>* Other names: 274901-16-5;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucagon response to hypoglycemia | Change in glucagon from before hypoglycemia clamp until after 45 min | 45 min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Catecholamine response to hypoglycemia | Change in catecholamines from before hypoglycemic clamp to 45 min | 45 min | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DPP-4, GLP-1, Glucagon, Catecholamines, Counterregulation, Insulin-treatment, Type 2 diabetes