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 HbA1c (primary end point) more than lixisenatide (estimated treatment difference -0.62% [95% CI -0.8; -0.4]; P < 0.0001), with more patients reaching HbA1c <7% (53 mmol/mol) and ≤6.5% (48 mmol/mol) versus lixisenatide (74.2% and 54.6% for liraglutide vs. 45.5% and 26.2% for lixisenatide; P < 0.0001 for both). Liraglutide reduced fasting plasma glucose more than lixisenatide (estimated treatment difference -1.15 mmol/L [95% CI -1.5; -0.8]; P < 0.0001). Liraglutide provided greater reduction in mean 9-point self-measured plasma glucose (P < 0.0001). However, postprandial glucose increments were smaller with lixisenatide for the meal directly after injection compared with liraglutide (P < 0.05), with no differences between treatments across all meals. Both drugs promoted similar body weight decrease (-4.3 kg for liraglutide, -3.7 kg for lixisenatide; 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.