The media has recently been filled with stories about how diabetes drugs like Ozempic (generic name semaglutide) might additionally be helpful not only for weight loss but also for alcohol use disorder (AUD). The HAMS alcohol harm reduction group on Facebook has also been abuzz with discussions of peptides, as such medications are known. So, what is the state of the research? Are these drugs effective for AUD?
The first ever placebo-controlled randomized trial of Ozempic for AUD was published in February by JAMA Psychiatry. The study was carried out by the University of North Carolina at Chapel Hill, in cooperation with the National Institute on Alcohol Abuse and Alcoholism. The lead investigator was Christian Hendershot, PhD.
There were 48 subjects in the study: 21 were categorized as overweight (BMI of 23 or more but less than 30) and 27 as obese (BMI of 30 or more). All subjects met criteria for AUD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).
On average, the participants had moderate AUD (meeting an average of 4.2 DSM-5 criteria). They consumed an average of 4.2 US standard drinks on drinking days, and drank an average of 20.2 days per month. When drinking and non-drinking days were combined, they consumed an average of 2.9 drinks per calendar day, with an average of 9.1 heavy drinking days per month and an average alcohol craving score of 12.0. None of them were previously seeking AUD treatment.
The Ozempic group showed significantly greater reductions than the placebo group in number of drinks per drinking day, number of heavy drinking days and alcohol craving scores.
The treatment consisted of injections of either a standard dose of Ozempic or a placebo, given once a week. Both the Ozempic group and the placebo group showed reductions in all alcohol-related variables over the nine-week experiment. However, there were significant differences between the Ozempic group and the placebo group on the amount of change shown for some of these variables.
The Ozempic group showed significantly greater reductions than the placebo group in number of drinks per drinking day, number of heavy drinking days and alcohol craving scores. Differences in number of drinks per calendar day and number of drinking days were not significant, however. As a side note, the Ozempic group showed weight loss but the placebo group did not.
Ozempic is a member of a class of drugs known as glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists). GLP-1 receptors are found in the pancreas, the brain, the nerves that control the digestive system, and a few other places. In nature, GLP-1 receptors can be activated by the hormone glucagon and by glucagon-like peptide-1 (GLP-1). GLP-1 receptors can also be activated by synthetic drugs such as Ozempic.
When the GLP-1 receptors in the pancreas are activated, they tell the pancreas to release more insulin. When the GLP-1 receptors in the brain are activated, they tell the brain that the stomach is full and that the person should stop eating. When the GLP-1 receptors in the nerves of the digestive system are activated, they tell the valve between the stomach and the intestine to close, among other things (the brain is also involved in issuing that instruction).
It is believed that Ozempic’s effects in the brain may cause it to reduce alcohol intake. Just as Ozempic tells the brain to be satisfied with smaller amounts of food, it seems to tell the brain to be satisfied with less alcohol. Ozempic’s effect on the valve between the stomach and the intestine might also be involved, because when this valve is closed, alcohol enters the bloodstream more slowly and people attain a lower BAC.
Although that recent study was the first ever placebo-controlled randomized trial of Ozempic for AUD, it was not the first such trial of any GLP-1 receptor agonist; the first concerned a drug named Bydureon (exenatide).
Overall, Bydureon did not significantly reduce heavy drinking days compared with placebo. However, when the results were analyzed by weight category, there were some significant findings.
The Bydureon trial, conducted in Sweden with 127 subjects and reported in JCI Insight in September 2022, was not a success. When the results of the entire group were examined, it was found that Bydureon did not significantly reduce the number of heavy drinking days compared with placebo.
However, when the drinking results were analyzed by weight category, there were some significant findings. Among 30 patients classed as obese, the Bydureon group did significantly better than the placebo group. For 45 patients classed as overweight, there was no significant difference between groups. And among 52 patients considered to have “normal” weight, the Bydureon group did significantly worse than the placebo group.
It is unclear whether the contrasting outcomes of the Ozempic and Bydureon trials were due to differences in the sample of subjects tested or to differences in the efficacy of the two drugs. Ozempic has been reported to be more effective than Bydureon for weight loss and control of diabetes.
More research is clearly required, and several further trials of diabetes drugs for AUD treatment have been registered with clinicaltrials.gov.
A Danish study is currently investigating whether Ozempic reduces alcohol intake in obese patients with AUD. A multisite trial with 86 locations is investigating the effects of Ozempic and other drugs on people with alcohol-related liver disease. And both a National Institute on Drug Abuse (NIDA) study and an Oklahoma State University study are currently recruiting subjects to investigate whether Ozempic reduces alcohol intake in patients with AUD.
The raft of upcoming studies, should enhance our understanding of how effective GLP-1 agonists are in treating AUD, and for whom.
Meanwhile, a University of Colorado study is recruiting subjects to look into whether Rybelsus (semaglutide in pill form) reduces alcohol consumption in treatment-seeking individuals with AUD. And a Swiss study, which is not yet recruiting, will investigate whether Ozempic increases alcohol abstinence in patients with obesity and fatty liver disease.
Other FDA approved GLP-1 agonists are dulaglutide (Trulicity), liraglutide (Victoza), lixisenatide (Adlyxin), and tirzepatide (Mounjaro). Of these four, only Mounjaro currently has registered clinical trials for AUD treatment—three of them, in fact.
A Danish study is currently recruiting patients to study the effects of Mounjaro on alcohol intake in patients diagnosed with schizophrenia and AUD. A University of Southern California study, not yet recruiting, will investigate whether it reduces the number of heavy drinking days in patients with moderate-to-severe AUD. And a study at Brigham and Women’s Hospital in Boston, also not yet recruiting, will investigate whether Mounjaro decreases cue-induced cravings for alcohol in people with AUD.
At the moment, then, there’s promise but not enough evidence to go on. The raft of upcoming studies, however, should enhance our understanding of how effective GLP-1 agonists are in treating alcohol use disorder, and for whom they are effective.
Photograph via PublicDomainPictures.net
