Can Semaglutide Curb Alcohol Cravings?

Credit: Adobe Stock/Pormezz

Over nine weeks, individuals who took once-weekly low-dose semaglutide — a glucagon-like peptide 1 (GLP-1) receptor agonist often used for diabetes and weight loss — drank less alcohol in a lab test, had lower alcohol cravings and smoked fewer cigarettes (if they were smokers). However, semaglutide did not reduce the number of drinking days overall.

Despite 29% and 11% of people living in the U.S. meeting lifetime and past-year criteria for alcohol use disorder (AUD), respectively, less than 10% report seeking treatment in the past year (of which only 2% received pharmacotherapy). This is of particular importance as alcohol use is considered a leading modifiable cause of morbidity and mortality in the U.S. — accounting for an estimated 178,000 deaths per year — and is linked to 2.6 million deaths per year globally.

“Underutilization of AUD medications is attributed to multiple factors, including few Food and Drug Administration (FDA)–approved therapies, limited awareness of these medications, and barriers related to stigma,” wrote a team of investigators led by Christian Hendershot, Ph.D., director of clinical research at University of Southern California’s Institute for Addiction Science and associate professor at Bowles Center for Alcohol Studies. “Reduced alcohol intake, irrespective of abstinence, is associated with improved health outcomes. Medications that facilitate reductions in alcohol use while achieving broad clinical uptake would fill a critical unmet need.”

The phase 2, double-blind, parallel-arm trial recruited 48 non-treatment-seeking patients with AUD at an academic medical center in the U.S. between September 2022 and February 2024. Participants were randomly assigned to receive placebo or semaglutide 0.25 mg/week for the first four weeks, 0.5 mg/week for the next four weeks and 1.0 mg for the remaining week.

The main objective was laboratory alcohol self-administration, which was measured both pre- and post treatment. Investigators also evaluated changes in alcohol cravings and consumption at outpatient visits.

The mean age of patients was 39.9 years and most (71%) were women. Patients receiving semaglutide consumed less alcohol post treatment during a laboratory self-administration task. They also had lower peak blood alcohol levels, meaning they didn’t get as intoxicated. However, semaglutide didn’t change whether people chose to drink or stay sober during the test.

While treatment with the GLP-1 receptor agonist did not impact the average drinks per calendar day or the number of drinking days, it significantly lowered the number of drinks per drinking day as well as weekly alcohol cravings. Compared with placebo, semaglutide was shown to predict reductions in heavy drinking over time and reduce the number of cigarettes per day among smokers.

Although patients in the semaglutide group reported some expected adverse events, most were mild in severity and no serious adverse events, treatment-related discontinuations or adverse interactions with alcohol were observed. Additionally, people taking semaglutide lost about 5% of their body weight during the study, while those on placebo didn’t lose weight.

The modest sample size and short treatment duration limited the study, according to investigators. Additionally, the low dosage of semaglutide — chosen to maximize safety and feasibility — may have minimized effects.

“These findings are especially notable in that this study used the 2 lowest clinical doses of semaglutide, whereas doses for weight reduction reach 2.4 mg/week,” investigators wrote. “Considering greater effects of semaglutide on other medical outcomes (eg, weight loss) with increasing dose and treatment duration, higher doses would presumably yield greater effects on alcohol reduction. However, safety profiles at higher doses in this population require careful evaluation.”

Investigators encourage future studies to include a larger sample size to determine the efficacy of GLP-1 receptor agonists and other incretin therapies for the treatment of AUD. They also suggest recruiting heavier drinkers into these trials, as patients enrolled in the current study consumed less alcohol than most treatment-seeking individuals.