Mechanism by Which Dapagliflozin Induces Euglycemic Ketoacidosis in Rats

Sodium-glucose transport protein 2 inhibitors (SGLT2i) are the most recent class of antidiabetic agents; however concerns have been raised about their potential to induce euglycemic ketoacidosis by an unknown mechanism. Here we report that dapagliflozin increases rates of hepatic ketogenesis (35±4 vs. 136±8 μmol/[kg-min], p Disclosure R.J. Perry: None. J.D. Song: None. Y. Wang: None. G.I. Shulman: Advisory Panel; Self; AstraZeneca, Janssen Research & Development, Merck & Co., Inc., Novo Nordisk Inc.. Research Support; Self; Gilead Sciences, Inc..