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2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial
The Lancet, 08/10/2012
Clinical Article
Gallwitz B et al. – The results of this long–term randomised active–controlled trial advance the clinical evidence and comparative effectiveness bases for treatment options available to patients with type 2 diabetes mellitus. The findings could improve decision making for clinical treatment when metformin alone is insufficient.
Methods- In this 2-year, parallel-group, non-inferiority double-blind trial, outpatients with type 2 diabetes and glycated haemoglobin A1c (HbA1c) 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 HbA1c 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 HbA1c measurement, and had at least one on-treatment HbA1c measurement.
- 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 HbA1c (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]; difference 0.20%, 97.5% CI 0.09-0.30), meeting the predefined non-inferiority criterion of 0.35%.
- Fewer participants had hypoglycaemia (58 [7%] of 776 vs 280 [36%] of 775 patients, p<0.0001) or severe hypoglycaemia (1 [<1%] vs 12 [2%]) with linagliptin compared with glimepiride.
- Linagliptin was associated with significantly fewer cardiovascular events (12 vs 26 patients; relative risk 0.46, 95% CI 0.23-0.91, p=0.0213).