Effect of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide on alcohol consumption in alcohol-preferring male vervet monkeys.

Rationale: Glucagon-like peptide-1 (GLP-1) receptor agonists reduce alcohol consumption in rodents and non-human primates. Semaglutide is a new long-acting GLP-1 receptor agonist, widely used in the clinic against type 2 diabetes and obesity. It is also reported to reduce alcohol intake in rodents.

Objectives: This study investigates the possible inhibitory effect of semaglutide on alcohol intake in alcohol-preferring African green monkeys.

Methods: We performed a vehicle-controlled study on male monkeys that had demonstrated a preference for alcohol. In the monkeys selected for voluntary alcohol drinking, alcohol consumption was measured for ten days at baseline (Monday to Friday for two weeks). During this period, the monkeys had access to alcohol 4 h per day and free access to water 24 h per day. After two weeks of baseline measurements, the monkeys were randomized to semaglutide or vehicle. Each group consisted of ten monkeys, and the two groups were balanced with respect to baseline alcohol intake. Following the baseline period, the monkeys were treated with escalating doses of semaglutide (up to 0.05 mg/kg) or vehicle subcutaneously twice weekly for two weeks during which period alcohol was not available. After uptitration, the monkeys had access to alcohol 4 h daily for 20 days (Monday to Friday for 4 weeks), and alcohol consumption was measured. During this alcohol exposure period, treatment with semaglutide (0.05 mg/kg twice weekly) or vehicle continued for three weeks followed by a one-week washout period.

Results: Compared to the vehicle, semaglutide significantly reduced alcohol intake. There were no signs of emetic events or changes in water intake.

Conclusions: These data demonstrate for the first time the potent effect of semaglutide in reducing voluntary alcohol intake in non-human primates and further substantiate the need for clinical trials investigating the effect of semaglutide in patients with alcohol-use disorder.