Introduction & Objective: To examine the effect of sodium-glucose co-transporter-2 inhibitor [SGLT2i] therapy alone or in combination with glucagon-like peptide-1 receptor agonist [GLP-1 RA] on beta-cell function [BCF] in T2D. HYPOTHESIS: the improvement in BCF with GLP-1 RA plus SGLT-2i would be superior to that with either agent alone.

Methods: Ninety patients received 3-hour OGTT: (i) before and after a single dose of drug (ACUTE study): placebo [PCB, n=15]; dapagliflozin [DAPA, n=25]; exenatide [EXE, n=25]; or both [DAPA/EXE, n=25], and (ii) after 1 and 4 months of therapy (CHRONIC study) with PCB, DAPA, EXE or DAPA/EXE. Matsuda Index [MI], Insulin Secretion [ΔI/ΔG)0-3h) and Disposition Index [DI=IS x MI] were calculated using standard formulae. MI was corrected for urinary glucose excretion.

Conclusion: Dapagliflozin and exenatide as monotherapy improve beta cell function (DI) acutely and chronically (4 months). Combination therapy with dapagliflozin plus exenatide leads to superior and sustained improvement in beta cell function (DI) compared to either drug alone. These data suggest that combination therapy with GLP-1 RA plus SGLT2i may enhance long-term preservation of beta-cell function in T2D patients.

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Disclosure

R.A. DeFronzo: Advisory Panel; AstraZeneca, Novo Nordisk, Boehringer-Ingelheim, Intarcia Therapeutics, Inc., Aardvark, Renalytix, Corcept Therapeutics, Alnylam Pharmaceuticals, Inc. Research Support; Boehringer-Ingelheim, AstraZeneca, 89bio, Inc., Amgen Inc., Medality, Corcept Therapeutics. Speaker's Bureau; AstraZeneca, Corcept Therapeutics, Renalytix. G. Baskoy: None. C.L. Triplitt: Speaker's Bureau; Novo Nordisk. Consultant; Eli Lilly and Company. Other Relationship; American Diabetes Association. E. Cersosimo: None. C. Solis-Herrera: Advisory Panel; Novo Nordisk, Bayer Inc. J.M. Adams: None. A.A. Hansis-Diarte: None. A. Gastaldelli: Consultant; Boehringer-Ingelheim. Other Relationship; Pfizer Inc., Eli Lilly and Company. Consultant; Merck Sharp & Dohme Corp. Advisory Panel; Novo Nordisk. Speaker's Bureau; Merck Sharp & Dohme Corp., Eli Lilly and Company. Advisory Panel; Pfizer Inc. Speaker's Bureau; Novo Nordisk. A. Chavez: None.

© 2024 by the American Diabetes Association
2024
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