2-year effi cacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: A randomised, double-blind, non-inferiority trial

摘要

Background Addition of a sulphonylurea to metformin improves glycaemic control in type 2 diabetes, but is associated with hypoglycaemia and weight gain. We aimed to compare a dipeptidyl peptidase-4 inhibitor (linagliptin) against a commonly used sulphonylurea (glimepiride). Methods In this 2-year, parallel-group, non-inferiority double-blind trial, outpatients with type 2 diabetes and glycated haemoglobin A 1c (HbA 1c) 6·5-10·0% on stable metformin alone or with one additional oral antidiabetic drug (washed out during screening) were randomly assigned (1:1) by computer-generated random sequence via a voice or web response system to linagliptin (5 mg) or glimepiride (1-4 mg) orally once daily. Study investigators and participants were masked to treatment assignment. The primary endpoint was change in HbA 1c from baseline to week 104. Analyses included all patients randomly assigned to treatment groups who received at least one dose of treatment, had a baseline HbA 1c measurement, and had at least one on-treatment HbA 1c measurement. This trial is registered at ClinicalTrials.gov, number NCT00622284. Findings 777 patients were randomly assigned to linagliptin and 775 to glimepiride; 764 and 755 were included in analysis of the primary endpoint. Reductions in adjusted mean HbA 1c (baseline 7·69% [SE 0·03] in both groups) were similar in the linagliptin (-0·16% [SE 0·03]) and glimepiride groups (-0·36% [0·03]; diff erence 0·20%, 97·5% CI 0·09-0·30), meeting the predefi ned non-inferiority criterion of 0·35%. Fewer participants had hypoglycaemia (58 [7%] of 776 vs 280 [36%] of 775 patients, p0·0001) or severe hypoglycaemia (1 [1%] vs 12 [2%]) with linagliptin compared with glimepiride. Linagliptin was associated with signifi cantly fewer cardiovascular events (12 vs 26 patients; relative risk 0·46, 95% CI 0·23-0·91, p=0·0213). Interpretation The results of this long-term randomised active-controlled trial advance the clinical evidence and comparative eff ectiveness bases for treatment options available to patients with type 2 diabetes mellitus. The fi ndings could improve decision making for clinical treatment when metformin alone is insuffi cient.