Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial

Background New treatments for type 2 diabetes mellitus are needed to retain insulin–glucose coupling and lower the risk of weight gain and hypoglycaemia. We aimed to investigate the safety and efficacy of liraglutide as monotherapy for this disorder. Methods In a double-blind, double-dummy, active-control, parallel-group study, 746 patients with early type 2 diabetes were randomly assigned to once daily liraglutide (1·2 mg [n=251] or 1·8 mg [n=247]) or glimepiride 8 mg (n=248) for 52 weeks. The primary outcome was change in proportion of glycosylated haemoglobin (HbA1c). Analysis was done by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NTC00294723. Findings At 52 weeks, HbA1c decreased by 0·51% (SD 1·20%) with glimepiride, compared with 0·84% (1·23%) with liraglutide 1·2 mg (difference −0·33%; 95% CI −0·53 to −0·13, p=0·0014) and 1·14% (1·24%) with liraglutide 1·8 mg (−0·62; −0·83 to −0·42, p<0·0001). Five patients in the liraglutide 1·2 mg, and one in 1·8 mg groups discontinued treatment because of vomiting, whereas none in the glimepiride group did so. Interpretation Liraglutide is safe and effective as initial pharmacological therapy for type 2 diabetes mellitus and leads to greater reductions in HbA1c, weight, hypoglycaemia, and blood pressure than does glimepiride. Funding Novo Nordisk A/S.