To evaluate the efficacy and safety of empagliflozin versus placebo as add-on therapy in patients with type 2 diabetes and inadequate glycemic control with linagliptin and metformin.
Patients with HbA1c ≥8.0% and ≤10.5% (≥64 and ≤91 mmol/mol) while receiving stable-dose metformin received open-label linagliptin 5 mg (n = 606) for 16 weeks. Subsequently, those with HbA1c ≥7.0 and ≤10.5% (≥53 and ≤91 mmol/mol) were randomized to receive double-blind, double-dummy treatment with empagliflozin 10 mg (n = 112), empagliflozin 25 mg (n = 111), or placebo (n = 110) for 24 weeks; all patients continued treatment with metformin and linagliptin 5 mg. The primary end point was the change from baseline in HbA1c after 24 weeks of double-blind treatment.
At week 24, empagliflozin significantly reduced HbA1c (mean baseline 7.96–7.97% [63–64 mmol/mol]) versus placebo; the adjusted mean differences in the change from baseline with empagliflozin 10 and 25 mg versus placebo were –0.79% (95% CI -1.02, -0.55) (–8.63 mmol/mol [-11.20, -6.07 mmol/mol]) and –0.70% (95% CI -0.93, -0.46) (–7.61 mmol/mol [-10.18, -5.05 mmol/mol]), respectively (both P < 0.001). Fasting plasma glucose and weight were significantly reduced in both empagliflozin groups versus placebo (P < 0.001 for all comparisons). More patients receiving placebo than empagliflozin 10 and 25 mg reported adverse events during double-blind treatment (68.2%, 55.4%, and 51.8%, respectively).
Empagliflozin treatment for 24 weeks improved glycemic control and weight versus placebo as an add-on to linagliptin 5 mg and metformin and was well tolerated.
