The effect of liraglutide, a long-acting glucagon-like peptide 1 derivative, on glycemic control, body composition, and 24-h energy expenditure in patients with type 2 diabetes.

Abstract

Glucagon-like peptide (GLP)-1 is a gut hormone that exerts incretin effects and suppresses food intake in humans, but its therapeutic use is limited due to its short half-life. This was a randomized, double-blind, parallel-group, placebo-controlled trial investigating the effect of the long-acting GLP-1 derivative liraglutide (NN2211) on glycemic control, body weight, body composition, and 24-h energy expenditure in obese subjects with type 2 diabetes. Thirty-three patients (mean +/- SD) aged 60.0 +/- 9.5 years, with HbA(1c) 7.5 +/- 1.2% and BMI 36.6 +/- 4.1 kg/m(2), were randomized to treatment with a single daily subcutaneous dose of 0.6 mg liraglutide (n = 21) or placebo (n = 12) for 8 weeks. In addition to weight and glycemic parameters, body composition was assessed by dual-energy X-ray absorptiometry (DEXA) scanning and 24-h energy expenditure in a respiratory chamber. After 8 weeks, liraglutide reduced fasting serum glucose (liraglutide, -1.90 mmol/l, and placebo, 0.27 mmol/l; P = 0.002) and HbA(1c) (liraglutide, -0.33%, and placebo, 0.47%; P = 0.028) compared with placebo. No change in body weight was detected (liraglutide, -0.7 kg, and placebo, -0.9 kg; P = 0.756). There was a nonsignificant trend toward a decrease in total fat mass (liraglutide, -0.98%, and placebo, -0.12%; P = 0.088) and toward an increase in lean body mass (liraglutide, 1.02%, and placebo, 0.23%; P = 0.118) in the liraglutide group compared with the placebo group. Twenty-four-hour energy expenditure was unaffected by the treatment (liraglutide, -12.6 kJ/h, and placebo, -13.7 kJ/h; P = 0.799). Eight weeks of 0.6-mg liraglutide treatment significantly improved glycemic control without increasing weight in subjects with type 2 diabetes compared with those on placebo. No influence on 24-h energy expenditure was detected.