Empagliflozin as Add-on Therapy in Patients With Type 2 Diabetes Inadequately Controlled With Linagliptin and Metformin: A 24-Week Randomized, Double-Blind, Parallel-Group Trial

OBJECTIVE 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. RESEARCH DESIGN AND METHODS Patients with HbA(1c) >= 8.0% and <= 10.5% (>= 64 and <= 91 mmol/ mol) while receiving stable-dose metformin received open- label linagliptin 5mg (n = 606) for 16 weeks. Subsequently, those with HbA(1c) >= 7.0 and <= 10.5% (>= 53 and <= 91 mmol/mol) were randomized to receive double-blind, double-dummy treatment with empagliflozin 10mg (n = 112), empagliflozin 25 mg (n = 111), or placebo (n = 110) for 24 weeks; all patients continued treatmentwithmetformin and linagliptin 5mg. The primary end point was the change from baseline in HbA(1c) after 24 weeks of double- blind treatment. RESULTS At week 24, empagliflozin significantly reduced HbA(1c) (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 20.79% (95% CI. 1.02,- 0.55) (-8.63 mmol/mol [-11.20,- 6.07 mmol/mol]) and 20.70% (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). CONCLUSIONS 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.