A randomized, double‐blind, placebo controlled, phase 3 trial to evaluate the efficacy and safety of cetagliptin added to ongoing metformin therapy in patients with uncontrolled type 2 diabetes with metformin monotherapy

Abstract Aim This trial was designed to assess the efficacy and safety of cetagliptin added to metformin in Chinese patients with type 2 diabetes who had inadequate glycaemic control with metformin monotherapy. Methods In total, 446 patients with type 2 diabetes on metformin monotherapy were randomized to receive the addition of once‐daily cetagliptin 100 mg, cetagliptin 50 mg and placebo in a 2:2:1 ratio for 24‐week double‐blind treatment. At week 24, patients initially randomized to cetagliptin 50 mg and placebo were switched to cetagliptin 100 mg for 28 weeks open‐label treatment. The primary endpoint was the change in haemoglobin A1c (HbA1c) from baseline, and the efficacy analyses were based on an all‐patients‐treated population using an analysis of co‐variance. Results After 24 weeks, both add‐on therapies led to greater glycaemic control. Reductions in HbA1c from baseline were −1.17 ± 0.794%, −1.23 ± 0.896% in cetagliptin 100 mg and 50 mg plus metformin group, respectively. No difference was observed between the cetagliptin 100 mg and 50 mg plus metformin group. Patients with higher baseline HbA1c levels (≥8.5%) experienced greater reductions in HbA1c. A significantly greater proportion of patients achieved an HbA1c <7.0% with cetagliptin 100 mg (49.4%) and cetagliptin 50 mg (51.1%) plus metformin than metformin monotherapy (14.4%). Both combination therapies also improved the homeostasis model assessment β‐function index and decreased systolic blood pressure. There was no increased risk of adverse effects with combination therapy, and both combination therapies were generally well tolerated. Conclusions The addition of cetagliptin once daily to metformin was more efficacious and well tolerated than metformin monotherapy in Chinese patients with type 2 diabetes who had inadequate glycaemic control with metformin monotherapy.