Durable HbA1c Reduction with Initial Combination Therapy with Metformin/Pioglitazone/Exenatide in Subjects with New-Onset Diabetes—Six-Year Follow-Up of the EDICT Study

Abstract

Background: We previously have shown that initial combination therapy with metformin/pioglitazone/exenatide (Triple Therapy) produced greater reduction in A1c than sequential add-on therapy in subjects with new onset of type 2 diabetes (T2D). Research Design and Methods: The EDICT study is a randomized open-label study in which newly diagnosed drug-naïve T2D subjects with new onset diabetes were randomized to receive Triple Therapy (n=132) or escalating dose of metformin followed by sequential addition of glipizide and then glargine insulin (Conventional Therapy) (n=146) to maintain A1c< 6.5. Here, we report the 6-year follow-up results. Results: Subjects receiving Triple Therapy experienced a significantly greater reduction in A1c after a mean follow-up of 6 years vs. Conventional Therapy (5.8% vs. 6.7%, p<0.001) (Figure 1). Further, more subjects maintained HbA1c <6.5% in the Triple Therapy group (25%) than in the Conventional Therapy (52%). Progression of carotid IMT (read blindly) was reduced by >50% (P<0.001) in Triple Therapy vs. Insulin Therapy. Conclusion: The results of this study demonstrate that combination therapy with metformin/pioglitazone/ exenatide in newly diagnosed T2DM patients produces greater and more reduction in A1c than sequential add-on therapy with metformin, sulfonylurea, and basal insulin. Disclosure M. Abdul-Ghani: None. C.L. Puckett: None. C.L. Triplitt: Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Eli Lilly and Company. Consultant; Self; Sanofi, Novo Nordisk Inc. D. Maggs: Stock/Shareholder; Self; Fractyl Laboratories, Inc.. Employee; Self; Fractyl Laboratories, Inc.. Stock/Shareholder; Spouse/Partner; Gelesis. Employee; Spouse/Partner; Gelesis. J.M. Adams: None. E. Cersosimo: Research Support; Self; AstraZeneca, VeroScience, LLC.. Speaker's Bureau; Self; AstraZeneca, Sanofi, Janssen Pharmaceuticals, Inc., Eli Lilly and Company. R.A. DeFronzo: Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc.. Advisory Panel; Self; AstraZeneca, Novo Nordisk Inc., Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc.. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Takeda Pharmaceuticals U.S.A., Inc..