2825-LB: Effect of Initial Combination Therapy with Pioglitazone plus Exenatide vs. Conventional Therapy on Body Composition and Bone Mineral Density: Results from the EDICT Study

Introduction and Objective: To examine the effect of 3-year combination therapy with exenatide plus pioglitazone on body composition and bone mineral density (BMD) in T2DM patients. Methods: 71 and 68 newly diagnosed T2DM patients, respectively, received initial combination therapy with metformin/pioglitazone/ exenatide (Triple Therapy), or metformin sequentially followed with glipizide and glargine insulin (Conventional Therapy) for 3 years. DEXA scan was done at baseline and at 3 years. Results: Subjects receiving Triple Therapy experienced a greater decrease in HbA1c -2.4±0.2% versus -1.5±0.2% (p<0.01), and the reduction in HbA1c was more durable. There was no significant change in mean body weight in either treatment groups. However, approximately one third of patients gained significant amount of weight, and weight gain was associated with a higher increase in HbA1c over time after month 6. The impact of increase in body weight on HbA1c was 2.5-fold greater in subjects receiving Conventional Therapy than Triple Therapy.Compared to Conventional Therapy, Triple Therapy was associated with 3.5% decrease in BMD in women above age 50 years. No significant change in BMD was observed in women <60 years and in men in both treatment groups. Conclusion: Combination therapy with GLP-1 RA plus pioglitazone produces greater and more durable reduction in HbA1c than Conventional Therapy, and prevents the increase in body weight over 3-year period. However, it does not prevent the decrease in BMD in women above 50 years of age. Disclosure S. Abdelgani: None. R.A. DeFronzo: Advisory Panel; Ended; AstraZeneca. Research Support; Current; AstraZeneca. Advisory Panel; Current; Novo Nordisk. Research Support; Current; Eli Lilly and Company. Advisory Panel; Current; Corcept Therapeutics. Speaker's Bureau; Current; Corcept Therapeutics. Consultant; Current; Alnylam Pharmaceuticals, Inc. Advisory Panel; Current; Regeneron Pharmaceuticals Inc., Aardvark. M. Abdul-Ghani: None. Funding NIH (R01DK24092-34) grant to RAD