Low-dose semaglutide cut lab alcohol use and craving in 48-person randomized trial

A phase 2 randomized trial published in JAMA Psychiatry found that weekly low-dose semaglutide lowered how much alcohol people drank in a laboratory task and how much they craved alcohol, compared with placebo, in adults with alcohol use disorder who were not seeking treatment ^[1][3]. UNC Health described it as the first randomized clinical trial of semaglutide for alcohol use disorder ^[2].

Researchers at a U.S. academic medical center screened 504 people and randomly assigned 48 with alcohol use disorder to semaglutide or placebo injections for nine weeks ^[3]. Enrollment ran from September 2022 through February 2024 ^[3]. Thirty-four of the 48 participants (71%) were female, and the average age was 39.9 years ^[3]. Dosing was deliberately low: 0.25 mg per week for the first four weeks, 0.5 mg per week for the next four, and a single 1.0 mg dose at the end ^[3]. That sits well below the doses used in diabetes and obesity care; the trial used the lowest clinical doses of the drug ^[2].

The main endpoint was a drinking session in the lab. A week before the first injection, each participant spent two hours with their preferred alcoholic drinks in a comfortable room, free to postpone drinking if they chose ^[2]. The same procedure was repeated after treatment ^[2]. Semaglutide reduced grams of alcohol consumed (beta, -0.48; 95% CI, -0.85 to -0.11; P = .01) and peak breath alcohol concentration (beta, -0.46; 95% CI, -0.87 to -0.06; P = .03), with medium to large effect sizes ^[3]. That second session took place after treatment week 8, when participants were on 0.5 mg per week ^[3].

Results from weekly self-report were mixed. Average drinks per calendar day and the number of drinking days were unchanged ^[3]. But drinks per drinking day fell (beta, -0.41; 95% CI, -0.73 to -0.09; P = .04), weekly alcohol craving fell on the Penn Alcohol Craving Scale (beta, -0.39; 95% CI, -0.73 to -0.06; P = .01), and heavy drinking declined faster than with placebo (beta, 0.84; 95% CI, 0.71 to 0.99; P = .04) ^[3].

Thirteen people in the study were current cigarette smokers ^[1]. Within that subgroup, daily cigarette counts dropped more on semaglutide than on placebo (beta, -0.10; 95% CI, -0.16 to -0.03; P = .005) ^[3]. UNC noted there is no approved medication that does both jobs, reducing alcohol and helping people stop smoking ^[2].

Senior author Klara Klein, MD, PhD, an assistant professor of medicine at UNC, said the results point to a possible role for these drugs in a condition where existing options go largely unused. "Larger and longer studies in broader populations are needed to fully understand the safety and efficacy in people with alcohol use disorder, but these initial findings are promising," she said ^[2]. Klein also said the first human trial of an older GLP-1 drug for alcohol use was inconclusive, while anecdotal reports of less drinking grew as semaglutide prescribing climbed ^[2].

Exactly how GLP-1 drugs blunt cravings is not established. Klein said preclinical work points to changes in brain reward processing ^[2].

Why it matters for patients

Semaglutide is FDA-approved as Ozempic for type 2 diabetes and as Wegovy for weight management. It is not approved for alcohol use disorder, and nothing in this trial changes its approved uses ^[2][3]. The three FDA-approved medications for alcohol use disorder are under-used, UNC noted ^[2]. Alcohol accounts for an estimated 178,000 U.S. deaths a year and is tied to liver disease, heart disease and cancer ^[2].

Several limits are worth keeping in view. The trial was small and short, the participants were not trying to quit drinking, and everyone received low doses, so the findings may not predict what happens in people already in treatment or on higher doses ^[2][3]. The authors say the ideal dose and treatment length for alcohol use disorder may turn out to be different from diabetes and obesity regimens ^[2]. Long-term effects on drinking have not been measured.

Klein reported consulting fees from Novo Nordisk and research contracts paid to her institution from Bayer, Boehringer-Ingelheim, Carmot, Diasome, Eli Lilly, Novo Nordisk, Rhythm Pharmaceuticals and vTv Therapeutics ^[3].

What happens next

The trial is registered as NCT05520775 ^[3]. The authors say larger, longer studies in broader groups are needed; no follow-up trial has been announced, and no timeline has been disclosed ^[2]. The work was funded by National Institute on Alcohol Abuse and Alcoholism grant R21AA026931 ^[2]. Whether any company will pursue an alcohol use disorder indication for semaglutide or another GLP-1 drug has not been reported.