246-OR: Contribution of Plasma Glucose and Hormones to the Acute Compensatory Rise in Endogenous Glucose Production (EGP) during Glucosuria in T2D Patients

Aim: To examine the role of plasma glucose (GLU), insulin (INS) and glucagon (GG) changes in EGP stimulation during glucosuria (UGE) following SGLT2i administration. Methods: Using tracer (3-3H-glucose), 30 T2D patients (Age=55±1y, BMI=32.2±0.7kg/m2, FPG=140±6mg/dl, A1c=7.3±0.1%) received three 300-min procedures at 2-weeks intervals: (I) control clamp (CON) with no glucose/hormone infusions; (II) pancreatic clamp (PAN) with somatostatin (0.75mg/h), basal replacement of insulin (0.1mU/kg.min) and glucagon (0.3ng/kg.min); (III) isoglycemic clamp (ISO) with variable dextrose infusion to maintain GLU equal to baseline. Prior to start of each clamp subjects received placebo (PCB, n=10) or dapagliflozin 10mg (DAPA, n=20). Results: After DAPA (CON), INS decreased (-7±1µU/ml) while GG increased (+10±1pg/ml) (both p Conclusion: DAPA-induced glucosuria stimulation of EGP cannot be entirely explained by the rise in plasma glucagon or decline in plasma insulin. Disclosure M. Alatrach: None. C. Agyin: None. N. Laichuthai: None. J.M. Adams: None. M. Abdul-Ghani: None. C.L. Triplitt: Consultant; Self; Abbott. Speaker9s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc. R.A. DeFronzo: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc. Speaker9s Bureau; Self; AstraZeneca, Novo Nordisk Inc. E. Cersosimo: None.