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-naïve [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 18 weeks, after which placebo patients switched to glimepiride 1-4 mg once daily and treatments continued for another 34 weeks. The primary endpoint was change from baseline in HbA1c after 18 weeks (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