Initial combination of linagliptin and metformin improves glycaemic control in type 2 diabetes: a randomized,...

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.

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.

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.

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.