Efficacy and Safety Comparison of Liraglutide, Glimepiride, and Placebo, All in Combination With Metformin, in Type 2 Diabetes The LEAD (Liraglutide Effect and Action in Diabetes)-2 study

OBJECTIVE - The efficacy and Safety of adding liraglutide (a glucagon-like peptide-1 receptor agonist) to Metformin were compared with addition of placebo or glimepiride to metformin in subjects previously treated With oral antidiabetes (OAD) therapy. RESEARCH DESIGN AND METHODS - In this 26-week, double-blind, double-dummy, placebo- and active-controlled, parallel-group trial, 1,091 subjects were randomly assigned (2:2:2:1:2) to once-daily liraglutide (either 0.6, 1.2, or 1.8 mg/day injected subcutaneous ), to placebo, or to glimepiride (4 mg once daily). All treatments were in combination therapy with metformin (1g twice daily). Enrolled subjects (aged 25-79 years) had type 2 diabetes, A1C of 7-11% (previous OAD monotherapy for >= 3 months) or 7-10% (previous OAD combination therapy for >= 3 months), and BMI <= 40 kg/m(2). RESULTS - A1C Values were significantly reduced in all liraglutide groups versus the placebo group (P<0.0001) with mean decreases of 1.0% for 1.8 mg liraglutide, 1.2 mg liraglutide and glimepiride and 0.7% for 0.6 mg liraglutide and -,in increase of 0.1% for placebo. Bod weight decreased in all liraglutide groups (1.8-2.8 kg) compared with an increase in the glimepiride group (1.0 kg; P < 0.0001). The incidence of minor hypoglycemia with liraglutide (similar to 3%) was comparable to that, with placebo but less than that with glimepiride (1,7%; P < 0.001). Nausea was reported by 11-19% of the liraglutide-treated subjects versus 3-4% in the placebo and glimepiride groups. The incidence of nausea declined over time. CONCLUSIONS - In subjects with type 2 diabetes, once-daily liraglutide induced similar glycemic control, reduced body weight, and lowered the Occurrence of hypoglycemia compared with glimepiride, when both had background therapy of metformin.