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


METHODS
Liraglutide was administered subcutaneously once daily (7 microg/kg for 7 weeks) to six female obese Göttingen 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.


CONCLUSIONS
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.
Raun
Kirsten
K
Department of Pharmacy Research 3, Diabetes Pharmacology, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Maaloev, Denmark. kira@novonordisk.com
von Voss
Pia
P
Knudsen
Lotte Bjerre
LB
D000818:Animals; D001067:Appetite Depressants / Q000627:therapeutic use*; D001823:Body Composition; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D002149:Energy Intake / Q000187:drug effects*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000502:physiology* / Q000627:therapeutic use; D000069450:Liraglutide; D009765:Obesity / Q000188:drug therapy*; D013552:Swine; D013556:Swine, Miniature
D001067:Appetite Depressants; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1