OBJECTIVE -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.RESEARCH DESIGN AND METHODS -Thirty-three patients (mean Ϯ SD) aged 60.0 Ϯ 9.5 years, with HbA 1c 7.5 Ϯ 1.2% and BMI 36.6 Ϯ 4.1 kg/m 2 , were randomized to treatment with a single daily subcutaneous dose of 0.6 mg liraglutide (n ϭ 21) or placebo (n ϭ 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.RESULTS -After 8 weeks, liraglutide reduced fasting serum glucose (liraglutide, Ϫ1.90 mmol/l, and placebo, 0.27 mmol/l; P ϭ 0.002) and HbA 1c (liraglutide, Ϫ0.33%, and placebo, 0.47%; P ϭ 0.028) compared with placebo. No change in body weight was detected (liraglutide, Ϫ0.7 kg, and placebo, Ϫ0.9 kg; P ϭ 0.756). There was a nonsignificant trend toward a decrease in total fat mass (liraglutide, Ϫ0.98%, and placebo, Ϫ0.12%; P ϭ 0.088) and toward an increase in lean body mass (liraglutide, 1.02%, and placebo, 0.23%; P ϭ 0.118) in the liraglutide group compared with the placebo group. Twenty-four-hour energy expenditure was unaffected by the treatment (liraglutide, Ϫ12.6 kJ/h, and placebo, Ϫ13.7 kJ/h; P ϭ 0.799).CONCLUSIONS -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. Diabetes Care 27:1915-1921, 2004G lucagon-like peptide (GLP)-1 has several effects that make it a potential candidate molecule for the treatment of type 2 diabetes. GLP-1 is a peptide hormone secreted from the L-cells in the lower gut, i.e., the distal jejunum, ileum, and colon/rectum, in response to ingestion of carbohydrates, lipids, and mixed meals (1-3). GLP-1 stimulates postprandial insulin secretion and acts as an incretin hormone, thus potentiating glucose-stimulated insulin release. The incretin effect refers to the increased insulin response elicited by oral glucose compared with the response resulting from an isoglycemic intravenous infusion (4). In addition, GLP-1 has a suppressive effect on glucagon release and hepatic glucose output (5).Treatment of hyperglycemia in type 2 diabetic patients with GLP-1 has received much attention, but additional therapeutic indications could be envisioned. Within the last few years, the ability of GLP-1 to decrease appetite and energy intake has been established (6). A reduced food intake would support weight reduction attempts in patients with type 2 diabetes. The appetite-reducing effect might partly be related to the ability...