Empagliflozin improves glycaemic and weight control as add-on therapy to pioglitazone or pioglitazone plus metformin in patients with type 2 diabetes: a 24-week, randomized, placebo-controlled trial

Aims: This study investigated the efficacy and tolerability of empagliflozin as add-on to pioglitazone +/- metformin in patients with type 2 diabetes (T2DM). Methods: Patients with HbA1c 7 and 10% were randomized and treated with once daily empagliflozin 10mg (n=165), empagliflozin 25mg (n=168) or placebo (n=165) as add-on to pioglitazonemetformin for 24weeks. Endpoints included changes from baseline in HbA1c (primary endpoint), fasting plasma glucose (FPG) and body weight at week 24. Results: Adjusted mean +/- standard error changes in HbA1c were -0.6 +/- 0.07% and -0.7 +/- 0.07% with empagliflozin 10mg and 25mg, respectively, vs. -0.1 +/- 0.07% with placebo (both p<0.001). More patients with HbA1c 7% at baseline achieved HbA1c <7% with empagliflozin 10mg (23.8%) and 25mg (30.0%) vs. placebo (7.7%) (both p<0.001). FPG decreased with empagliflozin (-0.94mmol/l for 10mg and -1.22mmol/l for 25mg) and increased with placebo (+0.36mmol/l; both p<0.001). Adjusted mean +/- standard error changes in weight were -1.62 +/- 0.21kg and -1.47 +/- 0.21kg with empagliflozin 10mg and 25mg, respectively, vs. +0.34 +/- 0.21kg with placebo (both p<0.001). Similar proportions of patients reported adverse events with empagliflozin (67.3-71.4%) and placebo (72.7%). Confirmed hypoglycaemia was reported by 1.2-2.4% of patients on empagliflozin and 1.8% on placebo. Conclusion: Empagliflozin 10mg and 25mg once daily for 24weeks as add-on to pioglitazone +/- metformin reduced HbA1c, FPG and weight and were well tolerated in patients with T2DM.