Several research studies, either in progress or in planning stages, are testing whether GLP-1 agonists can help people who have symptoms of an alcohol use disorder reduce drinking. The goal of the studies is not only to determine if these drugs reduce cravings, but also to understand the mechanisms by which this reduction occurs.

A pilot study of 20 patients, published in Nature’s Scientific Reports, appears to yield some clues. A key finding was that breath alcohol in this controlled study initially rose more slowly in the group of patients taking GLP-1; feelings of drunkenness, as reported by the study participants, followed the same trend.

This research comes amid growing awareness of the risk of alcohol and efforts by clinicians to help patients reevaluate their drinking. In 2023, the World Health Organization issued a statement saying that there is no safe amount of alcohol, that even a small or moderate amount of this carcinogen can damage health.

Study Details

Previous studies have suggested that people taking semaglutide and tirzepatide showed reduced sedative and stimulative effects of alcohol. As part of their research, Alexandra G. DiFeliceantonio, PhD, assistant professor at the Fralin Biomedical Research Institute at Virginia Tech, Roanoke, Virginia, and colleagues performed extensive searches and analyses of social media posts on GLP-1 agonists. This included the use of a machine-learning-based attribution mapping of about 68,250 Reddit posts related to GLP-1 or GLP-1/glucose-dependent insulinotropic polypeptide agonists.

To test if GLP-1s affect craving through biochemistry, the Virginia Tech team recruited participants from Roanoke and surrounding areas using flyers, the internet, and word-of-mouth referrals. Study participants had to occasionally drink alcohol, be aged 21 years or older, and have a BMI of 30 or greater.

The researchers worked with a final cohort of 20 participants, all of whom were White.

In the study group (n = 10), six patients were using semaglutide, two used liraglutide, and two used tirzepatide. The group had a mean BMI of 39.2 and consisted of nine women and one man.

In the control group (n = 10), no one used GLP-1 drugs. The group had a mean BMI of 37.98 and consisted of seven women and three men.

The test involved several drinking sessions, including one where participants were instructed to avoid eating beforehand. All participants started between 8 AM and 10 AM. They were given a snack of a Clif Bar to standardize caloric intake and ensure a similar gastric content prior to alcohol administration, researchers said. They checked the participants’ blood pressure, pulse, breath alcohol concentration, and blood glucose level before the start of the test.

Each drink was mixed at a 1:3 ratio of Tito’s Vodka to juice (cranberry or orange), and the number of drinks was calculated individually with the aim to raise blood alcohol to 0.1 g/dL.

Slower Onset of Drunkenness?

In the group of patients taking GLP-1 drugs, breath alcohol was measured at an average of 0.0208 g/dL at the 20-minute mark. For the control group, whose participants didn’t take GLP-1 drugs, the average breath alcohol was 0.0387 g/dL.

By the 60-minute mark, readings converged for the two groups at about 0.071 g/dL (control group: 0.0715; GLP-1 group: 0.0706), DiFeliceantonio told Medscape Medical News.

A similar gap appeared in the responses from participants about their feelings on a scale in response to the question “How drunk do you feel?” At the 20-minute mark, the mean response of the GLP-1 group was 1.0 on a 10-point scale, while the mean answer was 3.0 for the control group.

By the 60-minute mark, the GLP-1 group’s average score was 5.8, and the control group’s average was 5.4.

Potential Mechanism

A potential mechanism for the reported effects of GLP-1s on alcohol craving involves central nervous system or peripheral effects on gastric emptying, DiFeliceantonio and colleagues wrote. “Alcohol is not readily absorbed in the stomach but rather in the upper intestine, and slowed gastric emptying would therefore slow the effects of alcohol,” they explained. 

In this study, “we find support for this hypothesis, in that our participants taking GLP-1RAs [receptor agonists] had a delayed rise in BrAC [breath alcohol concentration] up to 20 minutes post alcohol consumption. This corresponded with a delayed increase in subjective feeling after alcohol consumption.”

More work needs to be done to understand the interplay of GLP-1 drugs and alcohol, but this may be something clinicians will eventually want to raise with patients as they prescribe these medicines, DiFeliceantonio, who is also the interim co-director at the Center for Health Behaviors Research at Virginia Tech, told Medscape Medical News.

“The patients might see changes in their experience with alcohol,” she explained. “If they do choose to drink, they should pay attention to how that alcohol is making them feel and how that might feel different than before they started taking the GLP-1 medication,” she said.

While they acknowledge that the study is small, DiFeliceantonio and coauthors concluded that the results provide “essential preliminary data (eg, effect sizes) for the design and development of larger randomized control trials testing the effectiveness of GLP-1RAs on reductions in alcohol use.”

STAR and STAR-T Trials

Among other, larger trials looking at these questions, the most advanced are two randomized, double-blind, placebo-controlled studies being done in collaboration: the National Institute on Drug Abuse (NIDA)’s STAR trial and the STAR-T trial, being conducted at Oklahoma State University, Stillwater, Oklahoma. The NIDA trial has enrolled about 52 patients, and the companion trial about 80 patients, according to Clinicaltrials.gov.

W. Kyle Simmons, PhD, professor of pharmacology and physiology and director of the Oklahoma State University Biomedical Imaging Center in Tulsa, Oklahoma, who is leading the STAR-T trial, noted that his team also wants to discover the mechanisms by which semaglutide might reduce alcohol consumption in patients with alcohol use disorder.

And “if it does happen,” he added, he and his colleagues also want to understand the mechanisms that might predict treatment response.

The results of the STAR-T trial are expected to be available in the coming months, Simmons told Medscape Medical News.

The Fralin Biomedical Research Institute supported the research reported in Scientific Reports. The authors reported having no relevant financial relationships. Simmons said that his lab served as a site in a phase 2 clinical trial funded by Altimmune, Inc., to assess the safety and efficacy of a GLP-1 RA for the treatment of alcohol use disorder.

Kerry Dooley Young is a freelance journalist based in Washington, DC. She has covered medical research and healthcare policy for more than 20 years.