Empagliflozin Monotherapy in Japanese Patients with Type 2 Diabetes Mellitus: a Randomized, 12-Week, Double-Blind, Placebo-Controlled, Phase II Trial

This study was designed to determine the efficacy and tolerability of empagliflozin monotherapy in Japanese patients with type 2 diabetes mellitus (T2DM). Patients with glycosylated hemoglobin (HbA1c) a parts per thousand yen7.0-a parts per thousand currency sign10% were randomized via an interactive web response system, and treated double-blind with empagliflozin 5, 10, 25, 50 mg, or placebo once daily for 12 weeks. The primary endpoint was change from baseline in HbA1c at week 12. Other endpoints included percentage of patients with HbA1c < 7.0% and changes from baseline in fasting plasma glucose (FPG), body weight, and systolic blood pressure (SBP) at week 12. A total of 547 patients were randomized and treated with empagliflozin 5 mg (n = 110), 10 mg (n = 109), 25 mg (n = 109), 50 mg (n = 110), or placebo (n = 109) for 12 weeks. Adjusted mean [95% confidence interval (CI)] differences vs. placebo in changes from baseline in HbA1c were -0.72% (-0.87, -0.57) with empagliflozin 5 mg, -0.70% (-0.85, -0.55) with 10 mg, -0.95% (-1.10, -0.80) with 25 mg, and -0.91 (-1.06, -0.76) with 50 mg (all p < 0.001). More patients with HbA1c a parts per thousand yen7.0% at baseline reached HbA1c < 7.0% with empagliflozin (19-33%) than placebo (3%). Compared with placebo, empagliflozin reduced FPG, body weight (p < 0.001 for all doses for both endpoints) and SBP (p = 0.001, p = 0.014 and p = 0.003 for empagliflozin 10, 25, and 50 mg, respectively). Adverse events were reported by 42% of patients receiving placebo and 33-38% of patients receiving empagliflozin. There were few reports of confirmed hypoglycemic adverse events or events consistent with urinary tract infection or genital infection in any treatment group. Empagliflozin monotherapy for 12 weeks in Japanese patients with T2DM reduced HbA1c, FPG, body weight and SBP, and was well tolerated.