Christian Hendershot, PhD, professor of Population and Public Health Sciences and director of Clinical Research at USC Institute for Addiction Science
The blockbuster drug semaglutide, better known as Ozempic for diabetes and Wegovy for obesity, could also help people cut down on their alcohol intake, according to new research led by Christian Hendershot, PhD, first author of the study, professor of Population and Public Health Sciences and director of Clinical Research at USC Institute for Addiction Science, and Klara Klein, MD, PhD, senior author, assistant professor at the Department of Medicine's Division of Endocrinology and Metabolism at the UNC School of Medicine.
The findings, published in JAMA Psychiatry, showed that weekly injections of semaglutide - compared with placebo injections - reduced alcohol craving, drinking quantity and the frequency of heavy drinking days in adults with symptoms of alcohol use disorder. Results also showed that after treatment, those in the semaglutide group consumed lower amounts of alcohol in the laboratory, as measured by grams of alcohol consumed and breath alcohol concentration.
Klara Klein, MD, PhD, assistant professor at the Department of Medicine's Division of Endocrinology and Metabolism at the UNC School of Medicine
The discovery could help address an important treatment gap: An estimated 178,000 U.S. deaths per year can be attributed to alcohol, which is linked to liver disease, cardiovascular disease and is a known cause of cancer, as noted recently by the U.S. Surgeon General. A significant proportion of American adults have met criteria for alcohol use disorder at some point in their lives - yet relatively few seek or receive treatment. The three drugs currently approved by the FDA to treat alcohol use disorder are under-utilized. The popularity of Ozempic and other GLP-1 receptor agonists could increase the chances of broad adoption of these treatments for alcohol use disorder.
The clinical trial
For the trial, researchers recruited 48 adults with alcohol use disorder who weren't actively seeking treatment. Alcohol use disorder is defined by a range of possible symptoms, including the inability to stop or control one's drinking despite negative consequences.
One week prior to the first injection, researchers invited participants to drink their preferred alcohol beverages over a two-hour period in a comfortable lab setting, with instructions to delay drinking if they wished. Researchers documented delays and drinks consumed.
Participants were then randomly assigned to receive weekly injections of Ozempic or a placebo for nine weeks, during which time their weekly drinking patterns were also measured. Afterward, participants and researchers returned to the drinking lab to repeat the process.
Results showed that after treatment, those in the semaglutide group consumed lower amounts of alcohol in the laboratory, as measured by grams of alcohol consumed and breath alcohol concentration.
Clinical assessments also indicated that semaglutide (compared to placebo injections) reduced weekly alcohol craving, reduced average drinks on drinking days, and led to greater reductions in heavy drinking days, relative to placebo. A key finding was that the magnitude of semaglutide's effects on several drinking outcomes appeared potentially greater than is often seen in similar studies with existing AUD medications, even though semaglutide was only administered at the lowest clinical doses.
Among a small subgroup of participants who smoked cigarettes at baseline, those treated with semaglutide had significantly greater reductions in average cigarettes per day compared to those in the placebo group. This finding is potentially important because there are no medications currently approved for both alcohol reduction and smoking cessation.
"The first clinical trial testing the impact of an older GLP-1 receptor agonist on alcohol use in humans was inconclusive," said Klein. "However, as prescription of semaglutide and similar medications escalated, anecdotal reports of reduced alcohol use became very common, and suggested the potential of these more potent therapies for treatment of alcohol use disorder."
Research is needed to understand the mechanisms by which GLP-1 receptor agonists reduce alcohol cravings. Dr. Klein says that preclinical studies suggest that these effects are likely mediated in the brain and involve changes in reward processing.
Although exciting, these data are preliminary and there is a need to learn more. As clinical use of this medication increases, the findings call for additional studies to evaluate long-term effect on alcohol consumption, and the ideal doses and treatment durations, which may be different from the current recommendations for people living with diabetes and obesity.
"These data suggest the potential of semaglutide and similar drugs to fill an unmet need for the treatment of alcohol use disorder," said Klein. "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."
About this study
In addition to Hendershot and Klein, other authors of the study are Michael Bremmer, Michael Paladino, Georgios Kostantinis, Thomas Gilmore, Neil Sullivan, Amanda Tow and Robyn Jordan, all of University of North Carolina at Chapel Hill; Sarah S. Dermody of Toronto Metropolitan University; Mark Prince of Keck School of Medicine; Sherry A. McKee of Yale School of Medicine; Paul J. Fletcher of University of Toronto; and Eric D. Claus of Pennsylvania State University.
This research was supported by National Institute on Alcohol Abuse and Alcoholism grant R21AA026931.
