Linagliptin monotherapy in type 2 diabetes patients for whom metformin is inappropriate: an 18-week randomized, double-blind, placebo-controlled phase III trial with a 34-week active-controlled extension

Aims: To investigate the efficacy and safety of linagliptin, a dipeptidyl peptidase-4 inhibitor, in type 2 diabetes mellitus (T2DM) patients for whom metformin was inappropriate. Methods: This 1-year double-blind study (ClinicalTrials.gov, NCT00740051) enrolled T2DM patients with inadequate glycaemic control, treatment-naive [glycated haemoglobin (HbA1c) 7.0-10.0%] or previously treated with one oral antidiabetes drug (HbA1c 6.5-9.0% before washout), ineligible for metformin because of contraindications (e. g. renal impairment) or previous intolerable side effects. Patients were randomized to monotherapy with linagliptin 5 mg once daily (n=151) or placebo (n=76) for 18weeks, after which placebo patients switched to glimepiride 1-4 mg once daily and treatments continued for another 34weeks. The primary endpoint was change from baseline in HbA1c after 18weeks (full-analysis set, last observation carried forward). Results: At week 18, adjusted mean difference in change from baseline HbA1c (8.1%) was -0.60% (95% confidence interval -0.88, -0.32; p<0.0001) (-0.39% with linagliptin, +0.21% with placebo). At week 52, mean HbA1c was decreased from baseline in both groups [linagliptin: -0.44%; placebo/glimepiride: -0.72% (observed cases)]. Adverse events occurred in 40.4 and 48.7% of linagliptin and placebo patients, respectively, during the initial 18 weeks. During the 34-week extension, patients receiving linagliptin experienced less hypoglycaemia (2.2% vs. 7.8%) and no weight gain (mean change from baseline of -0.2 and +1.3 kg, respectively) compared with glimepiride patients. Conclusions: In T2DM patients for whom metformin was inappropriate, linagliptin improved glycaemic control and was well tolerated, with less hypoglycaemia and relative weight loss compared with glimepiride.