A Phase IIb, randomized, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes

Aim: This Phase IIb, randomized, double-blind, placebo-controlled trial evaluated the efficacy, safety, tolerability and pharmacokinetics of empagliflozin in patients with type 2 diabetes. Methods: Four hundred and eight patients (treatment-naive or after a 4-week wash-out period) were randomized to receive empagliflozin 5, 10 or 25mg once daily, placebo or open-label metformin for 12weeks. The primary endpoint was change in haemoglobin A1c (HbA1c ) after 12weeks. Results: After 12weeks' treatment, empagliflozin showed dose-dependent reductions in HbA1c from baseline [5mg: -0.4%, 10mg: -0.5%, 25mg: -0.6%; all doses p<0.0001 vs. placebo (+0.09%)]. Fasting plasma glucose (FPG ) decreased with empagliflozin [5mg: -1.29mmol/l, 10mg: -1.61mmol/l, 25mg: -1.72mmol/l; all doses p<0.0001 vs. placebo (+0.04mmol/l)]. Body weight decreased in all empagliflozin groups (all doses p<0.001 vs. placebo). The incidence of adverse events (AEs ) was similar in the placebo (32.9%) and empagliflozin (29.1%) groups. The most frequently reported AEs on empagliflozin were pollakiuria (3.3% vs. 0% for placebo), thirst (3.3% vs. 0% for placebo) and nasopharyngitis (2.0% vs. 1.2% for placebo). AEs consistent with urinary tract infections (UTIs ) were reported in four (1.6%) patients on empagliflozin vs. one (1.2%) on placebo. Genital infections were reported in five (2%) patients on empagliflozin vs. 0% on placebo. No UTIs or genital infections led to premature discontinuation. Conclusions: In patients with type 2 diabetes, empagliflozin resulted in dose-dependent, clinically meaningful reductions in HbA1c and FPG , and reductions in body weight compared with placebo. Empagliflozin was well-tolerated with a favourable safety profile.