Liraglutide, a once-daily human glucagon-like peptide-1 analog, minimizes food intake in severely obese minipigs.

摘要

OBJECTIVES: To evaluate the efficacy of liraglutide, a new, stable, once-daily human analog of glucagon-like peptide-1, in a new animal model of obesity. RESEARCH METHODS AND PROCEDURES: Liraglutide was administered subcutaneously once daily (7 microg/kg for 7 weeks) to six female obese Gottingen minipigs. Food intake and feeding patterns were monitored using a novel automated feeding system that allowed continuous recording of food intake. RESULTS: Food intake was strongly suppressed. A steady-state level of reduced food intake was achieved within 3 weeks and was maintained for the remaining 4 weeks of the treatment period. During the 4-week steady-state period with liraglutide treatment, daily food intake was 7.3+/-0.3 megajoule (MJ) compared with 18.4+/-0.6 MJ in the pre-treatment period and 19.2+/-0.5 MJ in the post-treatment period (p<0.001). The food intake in the treatment period was equivalent to the amount of food that would have been offered to normal-weight pigs for maintenance. Body weight decreased 4.3+/-1.2 kg (4% to 5%) during the 7 weeks of treatment and increased 7.0+/-1.0 kg during the 7 weeks of post-treatment (p<0.01). Appetite suppression was quickly reversed within 4 days after termination of liraglutide administration. DISCUSSION: Overall, liraglutide was well tolerated and had a profound and persistent anorectic effect that resulted in weight loss. These results, in conjunction with the previously established glucose-lowering efficacy of liraglutide, suggest that the anorectic actions of liraglutide will be very important in clinical trials of both obese patients with type 2 diabetes and obese non-diabetic patients.