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

Abstract

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‐naïve or after a 4‐week wash‐out period) were randomized to receive empagliflozin 5, 10 or 25 mg once daily, placebo or open‐label metformin for 12 weeks. The primary endpoint was change in haemoglobin A1c ( HbA1c ) after 12 weeks. Results: After 12 weeks' treatment, empagliflozin showed dose‐dependent reductions in HbA1c from baseline [5 mg: −0.4%, 10 mg: −0.5%, 25 mg: −0.6%; all doses p < 0.0001 vs. placebo (+0.09%)]. Fasting plasma glucose ( FPG ) decreased with empagliflozin [5 mg: −1.29 mmol/l, 10 mg: −1.61 mmol/l, 25 mg: −1.72 mmol/l; all doses p < 0.0001 vs. placebo (+0.04 mmol/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.