Clinical Parameters, Fuel Oxidation, and Glucose Kinetics in T2D Patients Treated with Dapagliflozin plus Saxagliptin Combination

To investigate mechanisms responsible for the clinical and metabolic benefits observed with SGLT2i plus DPP-4i therapy, we randomized 30 T2D patients (A 1c =8.6±0.2%, BMI=33.1±1.9) to receive dapagliflozin 10 mg [DAPA], dapagliflozin/saxagliptin 10/5 mg [DAPA/SAXA] or placebo [PCB]. Baseline OGTT, glucose kinetics (3- 3 H-glucose), indirect calorimetry, HbA 1c , FPG, FFA, insulin, and glucagon were repeated after 16 weeks of therapy. Results: Insulin secretion (δI/δG) 0-120 min during OGTT increased (p Conclusion: DAPA/SAXA combination therapy was associated with improved glycemic control vs. DAPA due to the attenuation of the rise in EGP. Further, the increase in glucose Ox in combination with inhibition of lipid Ox and glucagon secretion inhibit ketone production which may reduce the risk of DKA. Addition of SAXA improves insulin secretion and prevents the glucagon elevation induced by DAPA. Disclosure Y. Qin: None. J.M. Adams: None. R.A. Martinez: None. A. Di Pino: None. H. Al Jobori: None. A.M. Ali: None. C.L. Triplitt: Speaker9s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Eli Lilly and Company. Consultant; Self; Sanofi, Novo Nordisk Inc. R.A. DeFronzo: Speaker9s 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. E. Cersosimo: Research Support; Self; AstraZeneca, VeroScience, LLC.. Speaker9s Bureau; Self; AstraZeneca, Sanofi, Janssen Pharmaceuticals, Inc., Eli Lilly and Company.