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.