Evidence Against an Important Role of Plasma Insulin and Glucagon Concentrations in the Increase in EGP Caused by SGLT2 Inhibitors

SGLT2 inhibitors lower plasma glucose but stimulate endogenous glucose production. The aim of the present study was to examine the effect of dapagliflozin on EGP while clamping plasma glucose, insulin and glucagon concentrations at their fasting level. 38 T2DM patients received an 8-hour measurement of EGP (3H-glucose) on 3 occasions. After a 3-hour tracer equilibration, subjects received: (i) dapagliflozin 10 mg (n=26) or placebo (n=12); (ii) repeat EGP measurement with plasma glucose concentration clamped at the fasting level; (iii) repeat EGP measurement with inhibition of insulin and glucagon secretion with somatostatin infusion and replacement of basal plasma insulin and glucagon concentrations. In Study 1, the change in EGP (baseline to last hour of EGP measurement) in subjects receiving dapagliflozin was 22% greater (+0.66 ±0.11 mg/kg.min, p