Effect of Empagliflozin on Free Fatty Acids and Ketone Bodies in Japanese Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial

Introduction We report a randomized, double-blind, placebo-controlled, 4-week study to investigate the effect of empagliflozin on free fatty acids and blood ketone bodies in Japanese patients with type 2 diabetes mellitus. Methods Patients (baseline mean [standard deviation] glycated hemoglobin 7.91% [0.80%]; body mass index 24.3 [3.2] kg/m 2 ) were randomized to empagliflozin 10 mg ( n = 20), empagliflozin 25 mg ( n = 19), or placebo ( n = 21) daily as monotherapy for 28 days. Meal tolerance tests (MTTs; breakfast, lunch, dinner) were performed on day − 1, day 1 (first day of treatment), and day 28. On day 1 and day 28, study drug was administered 1 h before breakfast. Free fatty acids and blood ketone bodies were measured before and 1, 2, and 3 h after each MTT, and the next morning (overnight fast). Results Empagliflozin significantly reduced plasma glucose and insulin and reduced body weight vs. placebo. Empagliflozin increased free fatty acids and total ketones bodies at day 1 and day 28. At day 28, the adjusted mean (95% confidence interval) difference vs. placebo in the time-corrected area under curve over 24 h for total ketone bodies was 67.1 (12.3, 121.8) µmol·h/L·h ( P = 0.017) with empagliflozin 10 mg and 178.1 (123.9, 232.2) µmol·h/L·h ( P