Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial

Summary Background Agonists of the glucagon-like peptide-1 (GLP-1) receptor provide pharmacological levels of GLP-1 activity, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors increase concentrations of endogenous GLP-1 and glucose-dependent insulinotropic polypeptide. We aimed to assess the efficacy and safety of the human GLP-1 analogue liraglutide versus the DPP-4 inhibitor sitagliptin, as adjunct treatments to metformin, in individuals with type 2 diabetes who did not achieve adequate glycaemic control with metformin alone. Methods In this parallel-group, open-label trial, participants (aged 18–80 years) with type 2 diabetes mellitus who had inadequate glycaemic control (glycosylated haemoglobin [HbA1c ] 7·5–10·0%) on metformin (≥1500 mg daily for ≥3 months) were enrolled and treated at office-based sites in Europe, the USA, and Canada. Participants were randomly allocated to receive 26 weeks' treatment with 1·2 mg (n=225) or 1·8 mg (n=221) subcutaneous liraglutide once daily, or 100 mg oral sitagliptin once daily (n=219). The primary endpoint was change in HbA1c from baseline to week 26. The efficacy of liraglutide versus sitagliptin was assessed hierarchically by a non-inferiority comparison, with a margin of 0·4%, followed by a superiority comparison. Analyses were done on the full analysis set with missing values imputed by last observation carried forward; seven patients assigned to liraglutide did not receive treatment and thus did not meet criteria for inclusion in the full analysis set. This trial is registered with ClinicalTrials.gov , number NCT00700817. Findings Greater lowering of mean HbA1c (8·5% at baseline) was achieved with 1·8 mg liraglutide (−1·50%, 95% CI −1·63 to −1·37, n=218) and 1·2 mg liraglutide (−1·24%, −1·37 to −1·11, n=221) than with sitagliptin (−0·90%, −1·03 to −0·77, n=219). Estimated mean treatment differences for liraglutide versus sitagliptin were −0·60% (95% CI −0·77 to −0·43, p