Liraglutide and a Calorie Restricted Diet Augments Weight Loss and Decreases Risk of Type 2 Diabetes and CVD.

Study Overview
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Brief Summary
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The goal of this study is to evaluate the hypothesis that the addition of liraglutide, a long-acting glucagon-like peptide 1 (GLP-1) analogue, to a calorie-restricted diet will lead to greater weight loss than will a calorie-restricted diet alone in subjects who are older (50 to 60 years of age), overweight/obese, and prediabetic. These individuals have been selected for study because they are at greatly increased risk to develop type 2 diabetes (2DM) and cardiovascular disease (CVD), and it is hypothesized that the addition of liraglutide to a calorie-restricted diet will significantly decrease risk of these adverse outcomes. There is considerable evidence that GLP-I compounds, including liraglutide, improve glycemic control in patients with manifest 2DM. However, there is relatively little information as to the potential utility of these compounds in nondiabetic individual at greatly increased risk of 2DM and CVD. This research proposal is aimed at providing some of this information by quantifying the effects of liraglutide, a long-acting GLP-1 analogue, on weight loss, insulin secretion, insulin action, and multiple CVD risk factors in a very high risk group-older, overweight/obese, prediabetic individuals. Furthermore, by using specific methods, not surrogate estimates, and avoiding the confounding effects of glucotoxicity, it will be possible to gain new insights into the effects of GLP-1 on insulin secretion and insulin action.

Official Title
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Addition of a Glucagon-like Peptide-1 to a Calorie Restricted Diet Augments Weight Loss and Decreases Risk of Type 2 Diabetes and Cardiovascular Disease.

Conditions
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Pre-diabetes, Older Adults

Intervention / Treatment
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* Drug: liraglutide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: IFG, or IGT BMI 27.0-37.0 kg/m2 Exclusion Criteria: DM, CAD, severe anemia, kidney or liver disease, hx of pancreatitis, gallstones, ETOH abuse, personnel or family history of medullary thyroid carcinoma or MEN-2

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>Both groups receive dietary weight loss intervention In addition one group received liraglutide and one group received placebo | Drug: Placebo<br>* Double blinded will receive study pen with same dosing instructions starting at 0.6 mg, and each week increase to 1.2 mg and finally 1.8 mg at week three.<br>|
| Active Comparator: liraglutide<br>Both groups receive dietary weight loss intervention In addition one group received liraglutide and one group received placebo | Drug: liraglutide<br>* Dosing begins at 0.6 mg subcutaneous injection and increases each week, to 1.2 mg and maximum dose of 1.8 mg.<br>* Other names: Victoza;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Weight Reported at 14 Weeks | Change in weight with caloric restriction plus liraglutide vs. caloric restriction and placebo over 14 weeks. | Baseline and 14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose-stimulated Insulin Secretion in Insulin AUC, Pmol/1x 4H | Absolute change in glucose-stimulated insulin secretion (GS-IS) associated with caloric restriction plus liraglutide vs. caloric restriction and placebo at 14 weeks | Baseline, 14 weeks | 
| Insulin Resistance in the Liraglutide vs.Placebo Group After Calorie Restriction | Mean (+/- SD) change in insulin resistance associated with caloric restriction plus liraglutide vs. caloric restriction and placebo. | Baseline, 14 weeks |