How an Obesity Drug Could Help Alcohol Use Disorder

The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide has made headlines as a US Food and Drug Administration (FDA)–approved treatment for type 2 diabetes (Ozempic) and obesity (Wegovy).

Recently, attention has turned to the possibility that semaglutide may have broader applications, including its potential positive impact on addictive behaviors such as reducing drug craving and alcohol consumption.

“There is some really interesting preclinical research in rodents and monkeys that shows that GLP-1 agonist molecules, like semaglutide, have the effect of reducing the consumption of not just food, but also alcohol, nicotine, cocaine and amphetamines,” Kyle Simmons, PhD, professor of pharmacology and physiology at Oklahoma State University Center for Health Sciences in Tulsa, told Medscape Medical News.

Some of that early research was conducted by Elisabet Jerlhag Holm, PhD, and colleagues at University of Gothenburg, Sweden.

“We have worked on GLP-1 and alcohol since 2012 and observe promising effects,” Holm told Medscape Medical News.

Her team published two studies earlier this year — one in Frontiers in Pharmacology and the other in eBioMedicine —demonstrating that semaglutide, in low doses, reduces alcohol intake in male and female rats.

“We have shown that semaglutide binds to the nucleus accumbens — an area of the brain associated with reward. We have also shown that semaglutide alters the dopamine metabolism when alcohol is onboard. This provides a tentative mechanism,” Holm said.

First Human Data

The preclinical data have fueled interest in testing the value of the GLP-1 receptor agonist in patient populations with addiction.

Simmons and colleagues have now published what is believed to be the first evidence in humans that semaglutide specifically reduces the symptoms of alcohol use disorder (AUD).

In a report published online on November 27 in The Journal of Clinical Psychiatry, they describe six patients (five of whom are female; mean age, 43 years) who received semaglutide treatment in the course of pharmacotherapy for weight loss.

All six screened positive for AUD on the Alcohol Use Disorders Identification Test (AUDIT), and all six showed significant improvement in their alcohol-related symptoms after starting semaglutide.

An AUDIT score > 8 is considered positive. The mean AUDIT score at baseline was 14. It fell to 4.5 on average after semaglutide treatment. The mean 9.5-point decrease in AUDIT scores with semaglutide was statistically significant (P <.001>

The patients were followed up from a few weeks to almost 9 months, and all of them had a reduction in AUD symptoms. At the various follow-up time points, all six patients had AUDIT scores consistent with “low-risk” drinking.

Strong Response at Low Doses

“There was a very strong response, even at a very low dose,” lead author Jesse Richards, DO, director of obesity medicine and assistant professor of medicine at the University of Oklahoma School of Community Medicine, Tulsa, told Medscape Medical News.

Three patients were treated with 0.5 mg of semaglutide weekly, two with 0.25 mg weekly, and one with 1 mg weekly. These doses are lower than those currently approved for treatment of type 2 diabetes and obesity.

Holm is not surprised by the results in these six patients. “Based on our preclinical data this outcome is expected. The data are promising and bigger studies needed,” she told Medscape Medical News.

Simmons is currently leading a randomized placebo-controlled trial to further test the impact of semaglutide on AUD.

The STAR (Semaglutide Therapy for Alcohol Reduction) study is funded by the Hardesty Family Foundation and Oklahoma State University Center for Health Sciences.

A sister study is also currently underway in Baltimore, funded by the National Institute on Drug Abuse.

Hopefully these studies will be able to “definitively tell us whether semaglutide is safe and effective for treatment” for AUD, Simmons said in a statement.

Despite being a major cause of preventable death worldwide, AUD currently has only three FDA-approved pharmacotherapies. However, there has been limited uptake of these drugs.

“There remains a significant treatment gap and need for new and novel or perhaps better tolerated or different mechanism treatment options for patients,” Richards said.

The preclinical and early clinical data provide a “signal” of a treatment effect for semaglutide in AUD, Richards said. The randomized controlled trials now underway should be concluding in the next 1-2 years, “at which point we’ll have a much better sense of the safety and efficacy of this drug for AUD,” he said.

The case series had no specific funding. Richards is on speakers bureaus for Rhythm Pharmaceuticals and Novo Nordisk and is on an advisory board for Rhythm Pharmaceuticals. Simmons is the recipient of a grant from the Hardesty Family Foundation to support an ongoing clinical trial of semaglutide in the treatment of AUD. Holm has no relevant disclosures.