Short-term effects of liraglutide and semaglutide on weight gain and adiposity by rats fed a Western diet.

GLP-1 receptor agonists are known to produce weight loss in people with obesity. Whether either drug can prevent weight gain by nonobese individuals has received little research attention. The present studies investigated the ability of liraglutide and semaglutide to prevent weight gain in male and female rats following the initiation of an obesity-promoting Western-style diet (WD). Because these drugs have been reported to produce gastric upset, we investigated whether either could prevent weight gain and increased adiposity at doses that failed to produce sickness. In Experiment 1a, 50 and 25 µg/kg doses (i.p.) of liraglutide produced significant conditioned taste avoidance (CTA), whereas 10 and 5 µg/kg doses did not. In Experiment 1b, daily administration of the 10 µg/kg dose of liraglutide over a 12-day test period following ad libitum WD initiation failed to prevent increases in body weight or adiposity relative to saline for either sex. Experiment 2 showed that 10 µg/kg of semaglutide, injected once every 3 days, significantly reduced WD-induced weight, and fat gain relative to saline controls. However, Experiment 3a showed that this dose, but not 5 or 3 µg/kg doses produced significant CTA for both sexes. Experiment 3b examined the effects of the 5 µg/kg i.p. dose of semaglutide, administered every 3 days and found no significant effect on WD-induced weight gain and only a transient effect on adiposity relative to WD-fed saline controls. The present findings suggest that the ability of GLP-1 receptor agonists to prevent weight and body fat gain may depend on malaise.