AIMS: To evaluate the effects of the sodium glucose cotransporter 2 (SGLT2) 
inhibitor empagliflozin added to metformin for 12 weeks in patients with type 2 
diabetes.
METHODS: This dose-ranging, double-blind, placebo-controlled trial randomized 
495 participants with type 2 diabetes inadequately controlled on metformin 
[haemoglobin A1c (HbA1c) >7 to ≤10%] to receive 1, 5, 10, 25, or 50 mg 
empagliflozin once daily (QD), or placebo, or open-label sitagliptin (100 mg 
QD), added to metformin for 12 weeks. The primary endpoint was change in HbA1c 
from baseline to week 12 (empagliflozin groups versus placebo).
RESULTS: Reductions in HbA1c of -0.09 to -0.56% were observed with empagliflozin 
after 12 weeks, versus an increase of 0.15% with placebo (baseline: 7.8-8.1%). 
Compared with placebo, empagliflozin doses from 5 to 50 mg resulted in 
reductions in fasting plasma glucose (-2 to -28 mg/dl vs. 5 mg/dl with placebo; 
p < 0.0001) and body weight (-2.3 to -2.9 kg vs. -1.2 kg; p < 0.01). Frequency 
of adverse events was generally similar with empagliflozin (29.6-48.6%), placebo 
(36.6%) and sitagliptin (35.2%). Hypoglycaemia rates were very low and balanced 
among groups. Most frequent adverse events with empagliflozin were urinary tract 
infections (4.0% vs. 2.8% with placebo) and pollakiuria (2.5% vs. 1.4% with 
placebo). Genital infections were reported only with empagliflozin (4.0%).
CONCLUSIONS: Once daily empagliflozin as add-on therapy to metformin was well 
tolerated except for increased genital infections and resulted in reductions in 
HbA1c, fasting plasma glucose and body weight in patients with type 2 diabetes 
inadequately controlled on metformin monotherapy.