352-OR: Combination Therapy with Dapagliflozin plus Exenatide on Endogenous Glucose Production: A Mechanism of Action Study

Abstract

Aim: To examine the mechanisms with which GLP-1 RA plus SGLT2i improve glycaemia versus each agent as monotherapy. Study Design: 21 T2D patients (Age= 51±2; BMI=31.2±0.7; A1C=7.9±0.2%, FPG= 172±8; mean PG OGTT [0-5h] =249±8) received 5-hour double tracer (3-3H-glucose IV/1-14C-glucose orally) OGTT and then were randomized to dapagliflozin (DAPA) 10 mg/d, exenatide (EXEN) 2 mg/wk, dapagliflozin plus exenatide (DAPA/EXEN) for 4 months. Results: Combination DAPA/EXEN therapy produced a completely additive effect to reduce HbA1c and near additive effect to decrease FPG and mean PG during OGTT. The additive effect of DAPA/EXEN resulted from: (1) decreased basal EGP; (2) increased urinary glucose excretion (UGE); (3) decreased rate of oral glucose appearance (RaO); (4) enhanced insulin secretion; (5) increased tissue glucose clearance. Of note, exenatide could not overcome the impaired suppression of EGP by dapagliflozin. Disclosure M. Alatrach: None. C. Agyin: None. J.M. Adams: None. O. Lavrynenko: None. N. Laichuthai: None. E. Cersosimo: None. C.L. Triplitt: Speaker’s Bureau; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Xeris Pharmaceuticals, Inc. A. Gastaldelli: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Inventiva Pharma, Novo Nordisk Inc. M. Abdul-Ghani: None. R.A. DeFronzo: None.