Linagliptin as add-on to empagliflozin and metformin in patients with type 2 diabetes: Two 24-week randomized, double-blind, double-dummy, parallel-group trials.

AIM: To evaluate the efficacy and safety of linagliptin vs placebo as add-on to empagliflozin and metformin in patients with type 2 diabetes. MATERIALS AND METHODS: Patients with inadequate glycaemic control despite stable-dose metformin received open-label empagliflozin 10 mg (study 1) or 25 mg (study 2) as add-on therapy for 16 weeks. Subsequently, those with HbA1c ≥7.0 and ≤10.5% (>53 and ≤91 mmol/mol) (N = 482) were randomized to 24 weeks' double-blind, double-dummy treatment with linagliptin 5 mg or placebo in study 1, or to linagliptin 5 mg or placebo in study 2; all patients continued treatment with metformin and empagliflozin 10 mg (study 1) or metformin and empagliflozin 25 mg (study 2). The primary endpoint was change from baseline (defined as the last value before first intake of randomized, double-blind treatment) in HbA1c at week 24. RESULTS: At week 24, HbA1c (mean baseline 7.82-8.04 [62-64 mmol/mol]) was significantly reduced with linagliptin vs placebo; adjusted mean (SE) differences in change from baseline in HbA1c with linagliptin vs placebo were -.32% (.10) (-3.59 [1.08] mmol/mol) ( P = .001) for patients on empagliflozin 10 mg and metformin, and -0.47% (0.10) (-5.15 [1.04] mmol/mol) ( P < 0.001) for patients on empagliflozin 25 mg and metformin. Adverse events were reported in more patients receiving placebo than in those receiving linagliptin: 55.5% vs 48.4% in study 1 and 58.9% vs 52.7% in study 2. CONCLUSIONS: Linagliptin as add-on to empagliflozin and metformin for 24 weeks improved glycaemic control vs placebo, and was well tolerated.

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 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. RESULTS: 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). 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.