Dipeptidyl Peptidase-4 Inhibition on Glucagon-like Peptide-1 (GLP-1)

Study Overview
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Brief Summary
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This research is being done to evaluate the effect of glucagon-like peptide-1 (GLP-1, a naturally occurring hormone) on insulin release and to examine whether there is extra insulin release when GLP-1 is not allowed to be rapidly inactivated.

Detailed Description
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The purpose of the present proposal is to 1) examine the role of dipeptidyl peptidase (DPP-4) inhibition on insulin release during a hyperglycemic clamp while GLP-1 is being infused and, 2) further elucidate the role of the metabolite of GLP-1, that is GLP-1 9-36 amide (GLP-1m). During stable and very reproducible elevated plasma glucose levels the effect of increased active incretin levels with DPP-4 inhibitors should result in increased plasma insulin levels. Therefore the aim of this protocol is to document whether plasma insulin levels are increased following GLP-1 infusion in the presence or absence of DPP-4 inhibitors. Additionally, the investigators have shown that some improvement in glucose homeostasis during GLP-1 administration is due in part to the metabolite of GLP-1, i.e. GLP-1 (9-36) amide (GLP-1m). Therefore, the investigators will also test the role of the latter by infusing GLP-1m when the volunteers are being treated with DPP-4 inhibitors.

Official Title
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The Effect of Dipeptidyl Peptidase-4 Inhibition on GLP-1 Induced Insulin Secretion and Glucose Turnover During Mild Stable Hyperglycemia in Young and Old Normal Volunteers

Conditions
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Glucose Homeostasis

Intervention / Treatment
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* Drug: Placebo
* Drug: Januvia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hct level of at least 34% for women and 36% for men Women of non-bearing potential and women of childbearing potential using adequate contraception Serum creatine level of less than 1.7 mg/dl Four groups: Age 21-45 (BMI between 18.50-24.99) & (BMI between 30-35) Age greater than 65 years (BMI between 18.50-24.99) & (BMI between 30-35) Exclusion Criteria: Pregnant and/or lactating females Women of childbearing potential not willing to use adequate contraception Hct below inclusion criteria Serum creatine level greater than 1.8 mg/dl Age less than 21 and age between 46-64 Diabetes mellitus BMI less than 18 and BMI greater than 35

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 1 tablet 100 mg once a day<br>* Other names: Sugar pill;|
| Active Comparator: Januvia<br> | Drug: Januvia<br>* 1 tablet 100 mg once a day<br>* Other names: Sitagliptin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Release Rate and Hepatic Glucose Release |  | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peripheral Glucose Utilization and Peripheral Glucagon Release |  | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy volunteers, GLP-1, Januvia, Sitagliptin