Initial combination of linagliptin and metformin improves glycaemic control in type 2 diabetes: a randomized, double-blind, placebo-controlled study

Aims: To evaluate the efficacy and safety of initial combination therapy with linagliptin plus metformin versus linagliptin or metformin monotherapy in patients with type 2 diabetes. Methods: In this 24‐week, double‐blind, placebo‐controlled, Phase III trial, 791 patients were randomized to one of six treatment arms. Two free combination therapy arms received linagliptin 2.5 mg twice daily (bid) + either low (500 mg) or high (1000 mg) dose metformin bid. Four monotherapy arms received linagliptin 5 mg once daily, metformin 500 mg or 1000 mg bid or placebo. Patients with haemoglobin A1c (HbA1c) ≥11.0% were not eligible for randomization and received open‐label linagliptin + high‐dose metformin. Results: The placebo‐corrected mean (95% confidence interval) change in HbA1c from baseline (8.7%) to week 24 was −1.7% (−2.0, −1.4) for linagliptin + high‐dose metformin, −1.3% (−1.6, −1.1) for linagliptin + low‐dose metformin, −1.2% (−1.5, −0.9) for high‐dose metformin, −0.8% (−1.0, −0.5) for low‐dose metformin and −0.6 (−0.9, −0.3) for linagliptin (all p < 0.0001). In the open‐label arm, the mean change in HbA1c from baseline (11.8%) was −3.7%. Hypoglycaemia occurred at a similar low rate with linagliptin + metformin (1.7%) as with metformin alone (2.4%). Adverse event rates were comparable across treatment arms. No clinically significant changes in body weight were noted. Conclusions: Initial combination therapy with linagliptin plus metformin was superior to metformin monotherapy in improving glycaemic control, with a similar safety and tolerability profile, no weight gain and a low risk of hypoglycaemia.