Efficacy and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, as add-on to metformin in type 2 diabetes with mild hyperglycaemia

Abstract

Aims: To evaluate the effects of the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin added to metformin for 12weeks 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 50mg empagliflozin once daily (QD), or placebo, or open-label sitagliptin (100mg QD), added to metformin for 12weeks. 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 12weeks, versus an increase of 0.15% with placebo (baseline: 7.8-8.1%). Compared with placebo, empagliflozin doses from 5 to 50mg resulted in reductions in fasting plasma glucose (-2 to -28mg/dl vs. 5mg/dl with placebo; p<0.0001) and body weight (-2.3 to -2.9kg vs. -1.2kg; 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. © 2013 John Wiley & Sons Ltd.