The popular weight management and type 2 diabetes medication semaglutide, sold under the brand names Wegovy, Ozempic, and Rybelsus, may reduce alcohol cravings and help people with alcohol use disorder (AUD) drink less, according to a case series published on November 27 in the Journal of Clinical Psychiatry.
In the first published evidence in humans, investigators found a significant reduction in the symptoms of alcohol use disorder in all six people taking the medication, says the lead author, Jesse Richards, DO, the director of obesity medicine and an assistant professor of medicine at the OU-TU School of Community Medicine in Tulsa, Oklahoma.
“These individuals had been prescribed semaglutide for weight loss, not AUD, but while they were on the medication, they spontaneously reported that they were drinking fewer drinks whenever they would drink alcohol, and they tended to drink less frequently as well,” says Dr. Richards.
“These findings mirror what many clinicians and patients have been reporting in terms of spontaneous reductions in alcohol use during treatment with newer GLP-1 receptor agonists,” says Christian Hendershot, PhD, a psychiatrist, associate professor, and researcher at the UNC School of Medicine in Chapel Hill. “These findings also align with reports that reductions in drinking can be substantial for some people,” adds Dr. Hendershot, who was not involved in the study.
People Taking Semaglutide Had Significant Reductions in Alcohol Use
To investigate how semaglutide may impact alcohol use, researchers reviewed the medical charts to find people who had been prescribed the drug for weight loss and also had alcohol use disorder (determined by a screening before they started the drug), according to the Alcohol Use Disorder Identification Test (AUDIT).
AUDIT includes questions about drinking frequency, binge drinking, blacking out due to drinking, and feelings around drinking. A score of 8 or higher indicates harmful alcohol use.
All six people who were identified had a reduction in symptoms of problematic drinking, with an average decrease of 9.5 points on AUDIT.
Most Participants Were Taking a Fraction of the Average Semaglutide Dose
The doses were quite low compared with the FDA approved levels of semaglutide, says Richards. “Five of the people were on either .25 or .5 milligram (mg); only one person was on the 1 mg dose. Currently, semaglutide is approved at 2 mg for the treatment of type 2 diabetes and 2.4 mg for the treatment of obesity,” he says.
These findings mark a significant step forward in our understanding of the potential therapeutic applications of semaglutide in the field of addiction medicine, says Richards.
This study begins to quantify the magnitude of reductions in alcohol consumption and alcohol use disorder symptoms during semaglutide treatment, says Hendershot.
It’s Possible That Many People Taking Semaglutide Are Consuming Less Alcohol
“It’s possible that this phenomenon is happening for large numbers of patients, so one interesting question is whether we can quantify the effects of these medications on drinking on a large scale. It’s now recognized that there’s no safe level of alcohol consumption, so even a modest reduction in consumption can be clinically meaningful,” says Hendershot.
Hendershot is currently part of a team of UNC researchers looking at whether semaglutide reduces alcohol consumption and cigarette use.
One unique aspect of this study from a medical standpoint is the diversity of the six participants. They included bariatric surgery patients who also had co-occurring medical and psychiatric conditions, says Hendershot.
Clinical trials are often overly selective and may have excluded these people from participating, he says. “Samples like this one are more representative of many medical settings. We eventually need to study the safety and efficacy of these medications in populations with more complex clinical and psychiatric presentations, as was the case in this study,” says Hendershot.
Weight Loss Medications Alter Brain Reward Pathways
If these findings are confirmed in randomized controlled trials, GLP-1 drugs like Ozempic could become known as the drugs that just keep on giving. Originally developed for diabetes, the medications work by causing the pancreas to release insulin by mimicking a hormone called GLP-1, or glucagon-like peptide 1. The first GLP-1 analogue, exenatide, was first approved for diabetes back in 2005.
But experts believe that GLP-1 analogues, which also include Mounjaro and Zepbound (tirzepatide), affect more than just the pancreas. The exact mechanism in weight loss is still unclear, but it’s thought that the drugs suppress hunger by slowing food’s passage through the stomach and preventing spikes and drops in blood sugar.
The medications also appear to bind to receptors on neurons in several parts of the brain, says Scott Kanoski, PhD, a neurobiologist and GLP-1 analogue researcher at USC Dornsife in Los Angeles.
“We know that these GLP-1 drugs act in the brain; there are receptors for GLP-1 in the brain reward system,” he says.
This was initially investigated as a mechanism through which the GLP-1 would reduce food craving and food intake, says Dr. Kanoski. “But we know in neuroscience that palatable foods — junk foods, for example — can engage the same brain reward chemistry as drugs of abuse,” he says.
This knowledge led researchers in the field to hypothesize that GLP-1 analogues might be effective in treating substance abuse disorders. Over the last several years, studies looking at GLP-1 analogues in animal models have confirmed that the drugs appear to alter the brain reward pathway.
Rats on a GLP-1, for instance, sought out less cocaine and oxycodone. African vervet monkeys predisposed to drinking alcohol drank less on liraglutide and exenatide.
More Research Is Needed to Expand on Initial Findings
Although the findings open new avenues for future research into the use of GLP-1 agonists in the treatment of addictive behaviors, further investigation in the form of large, controlled studies is needed to validate and expand upon these initial findings, wrote the authors.
This paper is a good example of where research in this area needs to go, says Kanoski. “We know these drugs are safe and effective for diabetes and weight loss treatment. If they can be pivoted for use with substance abuse disorders, I think that would be an exciting development. From the preclinical data so far, I think it’s certainly encouraging,” he says.
For Now, Experts Recommend Established Behavioral Treatments for Alcohol Use Disorder
Until the results of future placebo-controlled clinical trials are available, healthcare providers should recommend established behavioral treatments and medications that have been validated by the FDA for alcohol use disorder, says Richards.
Acamprosate, disulfiram, and naltrexone are the most common approved drugs used to treat alcohol use disorder, according to Substance Abuse and Mental Health Services Administration (SAMHSA).