Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin in type 2 diabetes mellitus (LEAD-2 Met).

Author(s): Nauck M, Frid A, Hermansen K, Shah NS, Tankova T, Mitha IH, Zdravkovic M, During M, Matthews DR, for the LEAD-2 Metformin Study Group

Affiliation(s): Diabeteszentrum Bad Lauterberg, Harz Germany.

Publication date & source: 2008-10-17, Diabetes Care., [Epub ahead of print]

Publication type:

Objective Efficacy and safety of adding liraglutide (a GLP-1 receptor agonist) to metformin were compared with adding placebo or glimepiride to metformin in subjects previously treated with oral antidiabetic (OAD) therapy. Research design and methods This 26-week, double-blind, double-dummy, placebo- and active-controlled, parallel-group trial randomized 1091 subjects (2:2:2:1:2) to once-daily liraglutide (either 0.6, 1.2, or 1.8 mg/day injected subcutaneously), or to placebo, or to glimepiride (4 mg once daily [QD]). All treatments were in combination therapy with metformin (1g twice daily; BD). Enrolled subjects (25-79 years) had type 2 diabetes, HbA(1c) 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 HbA(1c) values were significantly reduced in all liraglutide groups vs. placebo (P<0.0001), with mean decreases of 1.0% for liraglutide 1.8 mg, liraglutide 1.2 mg and glimepiride, 0.7% for liraglutide 0.6 mg, and an increase of 0.1% for placebo. Bodyweight decreased in all liraglutide groups (1.8 to 2.8 kg) compared to an increase in the glimepiride group (1.0 kg; P<0.0001). Incidence of minor hypoglycemia with liraglutide ( approximately 3%) was comparable to placebo but less than with glimepiride (17%; P<0.001). Nausea was reported by 11-19% of the liraglutide-treated subjects vs. 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 bodyweight, and lowered occurrence of hypoglycemia compared with glimepiride, when both had background therapy of metformin.