Aim: To examine the effect of SGLT2i on endogenous glucose production (EGP), tissue glucose disappearance (Rd), and urinary glucose excretion (UGE) following glucose ingestion.
Study Design: 28 type 2 diabetes [T2D] patients (Age= 51±2 y; BMI=31.2±0.7; A1C=7.9±0.2%) received 8-hour 3-3H-glucose infusion after an overnight fast. Previously shown, EGP suppression by dapagliflozin (DAPA) compared to placebo (PCB) (Δ=-0.02±0.02 vs. -0.45±0.03, p<0.01 mg/kg.min) was impaired. On a separate day, subjects were randomized to receive 5-hour double-isotope (IV 3-[3H]-glucose and oral [14C]-glucose) OGTT (75-g) preceded by PCB, DAPA 10 mg, EXEN 5 µg, or DAPA+EXEN. Oral [RaO], EGP, Total and Tissue Rd, and UGE were calculated.
Results: During 0-300-min, RaO was 65 g in DAPA, 59 g in PCB, 46 g in EXEN, and 48 g in DAPA+EXEN. UGE was 31±4 g in DAPA and 30±4 g in DAPA+EXEN, but only 3±1 g in EXEN and 10±3 g in PCB (p<0.001 vs. DAPA and DAPA+EXEN).
Conclusion: The post-OGTT rise in PG was significantly reduced after DAPA+EXEN vs. each drug alone. This resulted from lower oral glucose appearance with greater UGE. During the OGTT, EGP suppression with DAPA (Δ = -0.8±0.1 mg/kg.min) was less than with PCB, EXEN, and DAPA/EXEN (p<0.05-0.01), while EGP suppression with DAPA/EXEN was similar to PCB but required a higher rise in insulin (p<0.05). Tissue glucose clearance was unchanged by any therapy.
M. Alatrach: None. C. Agyin: None. N. Laichuthai: None. O. Lavrynenko: None. J.M. Adams: None. M. Abdul-Ghani: None. C.L. Triplitt: Speaker’s Bureau; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Xeris Pharmaceuticals, Inc. R.A. DeFronzo: None. E. Cersosimo: None.