Once-weekly semaglutide reduced problematic alcohol use, small study shows

Low-dose semaglutide reduced alcohol use over nine weeks of treatment compared to placebo, a small study found.

To evaluate the effects of once-weekly subcutaneous semaglutide on alcohol consumption and craving in outpatients with alcohol use disorder (AUD), researchers conducted a phase 2, double-blind, randomized, parallel-arm trial for nine weeks. Patients were enrolled at one U.S. academic medical center from September 2022 to February 2024 if they met the criteria for AUD in the past year or reported past-month use of more than seven (for women) or 14 (for men) standard drinks in a week, with two or more heavy drinking episodes (at least four drinks at a time for women and at least five more for men). Patients were excluded if they were currently seeking treatment for alcohol use or actively attempting to reduce consumption or had previously used glucagon-like peptide-1 (GLP-1) receptor agonists or other weight loss medications, had a body mass index less than 23 kg/m², or had other substance use disorders.

Forty-eight patients (71% female; mean age, 39.9 years) were randomized to receive semaglutide (0.25 mg/wk for four weeks, 0.5 mg/wk for four weeks, and 1.0 mg for one week) or placebo at weekly clinic visits. The primary outcome was laboratory alcohol self-administration, a standardized procedure that estimated voluntary alcohol consumption and the ability to delay drinking. Participants were given their preferred beverage and brand and could choose to delay drinking for up to 50 minutes for a monetary reward, then were instructed to consume at their preferred pace for 120 minutes. The amount of alcohol consumed was assessed by breath measurements. Weekly consumption was assessed using calendars and daily logs to record average drinks per calendar day. Secondary and exploratory outcomes, including prospective changes in alcohol consumption and craving, were assessed at outpatient visits. Results were published Feb. 12 by JAMA Psychiatry.

Low-dose semaglutide reduced the amount of alcohol consumed during laboratory sessions, with evidence of medium to large effect sizes on grams of alcohol consumed (β, −0.48 [95% CI, −0.85 to −0.11]; P=0.01) and peak breath alcohol concentration (β, −0.46 [95% CI, −0.87 to −0.06]; P=0.03). Semaglutide did not affect average drinks per calendar day or number of drinking days per week but significantly reduced drinks per drinking day (β, −0.41 [95% CI, −0.73 to −0.09] P=0.04) and weekly alcohol craving (β, −0.39 [95% CI, −0.73 to −0.06]; P=0.01), with greater reductions in heavy drinking over time relative to placebo (β, 0.84 [95% CI, 0.71 to 0.99]; P=0.04). Also, semaglutide resulted in greater relative reductions in cigarettes per day in a subsample of patients (β, −0.10 [95% CI, −0.16 to −0.03]; P=0.005).

The researchers concluded that low-dose semaglutide may reduce craving and some drinking outcomes, justifying larger clinical trials to evaluate diabetes drugs for alcohol use disorder. They noted that the FDA has approved three drugs for alcohol use since 1951, while diabetes drug options have increased by 20-fold in comparison.

“[T]hese treatments could have broad clinical infiltration, with potential to bypass many traditional impediments to the uptake of AUD medications, including low public and provider awareness and stigma toward AUD treatments,” the authors wrote. “Importantly, the increasing clinical uptake of GLP-1 [receptor agonists] would presumably reduce prescribing barriers, including in primary care, where AUD treatments have proven difficult to bring to scale.”