Can semaglutide curb drinking?

The glucagon-like peptide 1 receptor agonist (GLP-1RA) semaglutide has the potential to reduce alcohol cravings and consumption in adults with alcohol use disorder (AUD), as shown in a phase II study.

In a post-treatment alcohol self-administration task, participants who received low-dose semaglutide vs placebo consumed less alcohol, with medium to large effect sizes for grams of alcohol consumed (β, −0.48, 95 percent confidence interval [CI], −0.85 to −0.11; p=0.01) and peak breath alcohol concentration (β, −0.46, 95 percent CI, −0.87 to −0.06; p=0.03). [JAMA Psychiatry 2025;doi:10.1001/jamapsychiatry.2024.4789]

Compared with placebo, semaglutide was also associated with markedly reduced drinks per drinking day (β, −0.41, 95 percent CI, −0.73 to −0.09; p=0.04) and weekly alcohol craving (β, −0.39, 95 percent CI, −0.73 to −0.06; p=0.01). A significant treatment-by-time interaction (p=0.04) emerged. This indicated  that the semaglutide group experienced greater reductions in heavy drinking days over time compared with the placebo group (β, 0.84, 95 percent CI, 0.71–0.99).

In a subgroup analysis of current smokers, semaglutide treatment also led to greater reductions in cigarettes smoked per day over time compared with placebo (β, −0.10, 95 percent CI, −0.16 to −0.03; p=0.005).

Semaglutide had no significant effect on number of drinks per calendar day and the proportion of abstinent vs drinking days. As for body weight, a decrease of 5.05 percent with semaglutide and an increase of 0.18 percent with placebo was observed (time-by-treatment interaction: β, −0.07, 95 percent CI, −0.08 to −0.05; p<0.001). No marked changes were seen for haemoglobin A_1c, blood pressure, or depression scores.

AUD medications lag

According to the authors, the findings may have important implications, given the limited availability of approved medications for AUD.

“Since the FDA approval of the first AUD medication (disulfiram) in 1951, only two medications (naltrexone and acamprosate) have received subsequent FDA approval for AUD. The rate of 1 new approval every 20 to 25 years is inadequate and is in stark contrast with the pace of FDA approvals for diabetes medications, which now outnumber AUD medication approvals 20-fold,” they said. [Annu Rev Pharmacol Toxicol 2024;64:255-275; Handb Exp Pharmacol 2020;258:443-462]

“Considering both the rapid adoption of GLP-1RAs and the demonstrated health benefits of net reductions in alcohol use, GLP-1RA–related reductions in consumption—when considered at large scale—could lead to improved health outcomes that are not currently appreciated,” they added.

If subsequent phase II and phase III clinical trials demonstrate the utility of GLP-1RAs in the treatment of AUD, the already extensive use of such medications presents a favourable context for medication repurposing, with the potential to mitigate the substantial treatment gap observed in AUD management, the authors pointed out. [N Engl J Med 2023;389:2486-2494]

Non–nontreatment-seeking participants

The study included 48 participants (mean age 39.9 years, 71 percent female, 81 percent White, mean BMI 32.1 kg/m²) with AUD who were not seeking treatment. These participants were randomly assigned to receive semaglutide (0.25 mg/week for 4 weeks, 0.5 mg/week for 4 weeks, and 1.0 mg for 1 week) or placebo. Treatment was administered subcutaneously during weekly clinic visits.

Adverse effects that occurred in participants treated with semaglutide were mostly mild. There were no reports of serious adverse events, adverse interactions with alcohol, or treatment-related discontinuations.

“The focus on nontreatment-seeking participants has important considerations, one being that semaglutide-related reductions in drinking quantity occurred [in the absence of] volitional attempts to reduce drinking. In contrast to treatment-seeking participants, this sample is arguably representative of the majority of those with AUD exposed to GLP-1RAs in general medical settings,” the authors noted.