Effect of Exenatide on Weight and Metabolic Profile in Obese Insulin-Resistant Individuals and Results after Drug Discontinuation

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 839-872-Diabetes & Obesity Management
Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-854
James Kuang Tam*1, Tracey L McLaughlin2, Cindy A Lamendola3, Kimberly Dana Lerner4, Marcia Peck5 and Li Fen Liu6
1Stanford University Medical Center, Stanford, CA, 2Stanford University School of Medicine, Stanford, CA, 3Stanford Univ, Menlo Park, CA, 4Boulder Medical Center, Boulder, CO, 5Sutter East Bay Medical Foundation, Piedmont, CA, 6Stanford University, Palo Alto, CA
Background

Exenatide is a GLP-1 agonist and exerts its influence on satiety, resulting in weight loss.   While it is known that exenatide results in weight loss, it is not known whether weight loss is maintained after drug discontinuation. 

Objective

We sought to evaluate persistence of weight and metabolic benefits of exenatide in moderately-obese prediabetics one year after discontinuing the drug.

Methods

We recruited healthy volunteers with BMI 25-36 kg/m2 and prediabetes diagnosed via oral glucose tolerance testing.  Sixty-six obese insulin-resistant subjects qualified for the study.  In a double blinded, randomized controlled design, 34 patients were assigned to placebo and 32 patients were assigned to exenatide.  Exenatide was started at 5 mcg twice a day for 4 weeks and then increased to 10 mcg twice a day for 26 weeks and then discontinued at week 30.  For the first 16 weeks all subjects were placed on a hypocaloric diet with a calorie deficit of 750 kcal/day and biweekly visits with study dietitians to review weight and food diary.  After week 16, no further dietary advice was provided and patients were allowed to eat as they wished, although they continued on their assigned study drug. Weight, fasting glucose, 2 hour oral glucose tolerance testing, fasting lipid panel, and insulin levels were measured at 0, 16, 30 weeks, and 1 year.

Results

In the exenatide group, subjects lost 7.1 kg compared to the placebo group which lost 6.8 kg at 30 weeks compared to their baseline weights (p=0.68).  At one year follow up, subjects in the exenatide group subjects had lost 3.5 kg versus 3.3 kg in the placebo group compared to baseline (p=0.93).  During week 30 to 1 year, the exenatide group regained 58.8% and placebo 61.1% of the weight lost during the previous 30 weeks (p=0.77).  27.6% of subjects in the exenatide group converted from either impaired fasting glucose or glucose tolerance to normal fasting glucose or glucose tolerance at 30 weeks versus 25.9% of subjects in the placebo group.  15.8% of subjects in the exenatide group converted from either impaired fasting glucose or glucose tolerance to normal fasting glucose or impaired glucose tolerance vs. 18.8% in the placebo group at the 1 year interval. 

Conclusion

Exenatide results in weight loss and increased conversion of insulin resistant to non-insulin resistant states.  While subjects receiving exenatide benefit from weight loss, approximately 58.8% of this loss is regained within 1 year.

Nothing to Disclose: JKT, TLM, CAL, KDL, MP, LFL

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm