Once-Daily Liraglutide Versus Lixisenatide as Add-on to Metformin in Type 2 Diabetes: A 26-Week Randomized Controlled Clinical Trial

OBJECTIVE To compare the efficacy and safety of liraglutide versus lixisenatide as add-on to metformin in patients with type 2 diabetes not achieving adequate glycemic control on metformin alone. RESEARCH DESIGN AND METHODS In this 26-week, randomized, parallel-group, open-label trial, 404 patients were randomized 1:1 to liraglutide 1.8 mg or lixisenatide 20 µg as add-on to metformin. Liraglutide was administered once daily at any time of the day. Lixisenatide was administered once daily within 1 h prior to the morning or evening meal. RESULTS At week 26, liraglutide reduced HbA 1c (primary end point) more than lixisenatide (estimated treatment difference −0.62% [95% CI −0.8; −0.4]; P 1c P P P P P = 0.23). The most common adverse events in both groups were gastrointestinal disorders. Greater increases in pulse, lipase, and amylase were observed with liraglutide. Hypoglycemic episodes were rare and similar between the two treatments. CONCLUSIONS At the dose levels studied, liraglutide was more effective than lixisenatide as add-on to metformin in improving glycemic control. Body weight reductions were similar. Both treatments were well tolerated, with low risk of hypoglycemia and similar gastrointestinal adverse event profiles.