Weight-loss drug semaglutide reduces heavy alcohol drinking in new clinical trial

A new clinical trial reveals that a popular weight-loss medication helps people with both obesity and alcohol use disorder reduce their frequency of heavy drinking. The results suggest that these hormone-mimicking drugs might offer a novel and effective treatment path for millions of people struggling to control their alcohol intake. The findings were recently published in The Lancet.

Alcohol use disorder is a chronic brain condition characterized by a loss of control over drinking habits and a compulsive need to consume alcohol. This condition accounts for roughly five percent of deaths worldwide each year. It is a major driver of liver disease, cardiovascular problems, and various forms of cancer.

Despite decades of scientific investigation, the United States Food and Drug Administration has approved only three medications to treat the disorder. These existing options are disulfiram, acamprosate, and naltrexone. Because these existing drugs are not universally effective, medical professionals have actively searched for alternative approaches.

“Very few medications are currently approved for alcohol use disorder, and these are vastly underutilized. A new option that is more accessible and more effective could be a gamechanger for closing the treatment gap,” said George Koob, a study co-author and director of the National Institute on Alcohol Abuse and Alcoholism, in a press release from the National Institutes of Health.

Recently, a class of drugs known as glucagon-like peptide-1 receptor agonists has captured the attention of addiction researchers. Originally designed to treat diabetes and obesity, these medications mimic a hormone naturally produced in the small intestine and the brain. This native hormone regulates digestion, blood sugar, and overall appetite.

The hormone also interacts with the brain’s reward pathways. When a person consumes rich food or alcohol, these neural pathways release chemicals that create feelings of profound pleasure. Researchers suspect that by altering how the brain processes these rewards, the medications might reduce the fundamental desire to drink. Semaglutide, the active ingredient in brand-name drugs like Wegovy and Ozempic, belongs to this drug class.

Earlier experiments in animal models hinted that these medications could suppress the drive to consume alcohol. Later, large population studies showed that human patients taking the drugs for diabetes had fewer alcohol-related hospital visits. However, initial clinical trials focusing on alcohol use in humans yielded mixed results.

One previous human trial found that the medication did not produce a statistically significant reduction in drinking for the overall test group. Yet, a subset of participants in that trial who had obesity seemed to respond strongly to the treatment. This observation prompted a highly targeted investigation.

A research team led by Mette Kruse Klausen, a medical doctor at Copenhagen University Hospital, decided to test semaglutide in a specific population. They focused entirely on patients actively seeking treatment for alcohol use who also lived with obesity. The research group included corresponding author Anders Fink-Jensen of Copenhagen University Hospital, along with scientists from the United States National Institutes of Health.

To conduct the study, the investigators designed a randomized, double-blind, placebo-controlled trial. This setup is widely considered the gold standard in medical research because it prevents both the patients and the doctors from knowing who receives the active drug. The trial took place at a single clinical center in Denmark.

The researchers enrolled 108 adult participants, split almost evenly between men and women. Every participant met the clinical criteria for moderate to severe alcohol use disorder. They also had a body mass index of thirty or higher, which falls into the medical category of obesity.

The body mass index is a standard measurement that relates a person’s weight to their height. Participants were divided evenly into two groups of 54 people. One group received a weekly injection containing 2.4 milligrams of semaglutide, while the other group received a weekly placebo injection containing harmless salt water. The trial lasted for 26 weeks, giving the drug ample time to reach its maximum dosage in the patients’ systems.

The research team went to great lengths to ensure the study remained truly blind. The semaglutide injection pen makes a distinct mechanical clicking sound when operated. To prevent participants from guessing their group based on this sound, the patients wore blindfolds and listened to music through headphones during their weekly injections.

In addition to the injections, all participants received up to ten sessions of cognitive behavioral therapy. This form of psychological treatment helps patients identify and change destructive thought patterns and behaviors. The therapy focused on building motivation, managing intense cravings, and preventing relapses into heavy drinking.

Throughout the trial, the participants reported their daily alcohol intake using a highly validated tracking method. The researchers specifically looked at the number of heavy drinking days each person experienced. For men, a heavy drinking day involved consuming at least 60 grams of pure alcohol, while for women, the threshold was set at 48 grams.

The results of the 26-week intervention were highly encouraging for the active treatment group. Participants receiving semaglutide experienced a 41.1 percentage point reduction in their heavy drinking days. In contrast, the placebo group saw a 26.4 percentage point reduction during the same timeframe.

This outcome resulted in an estimated treatment difference of 13.7 percentage points between the two groups. Beyond the primary measure of heavy drinking days, the medication produced positive changes across a variety of secondary metrics. The total volume of alcohol consumed dropped substantially more in the semaglutide group than in the placebo group.

Patients receiving the active drug also reported fewer individual drinks per drinking day. Their overall alcohol craving scores decreased measurably compared to those receiving the placebo. To ensure the patients were reporting accurately, the scientists used objective blood tests to track recent alcohol use.

Specifically, the researchers measured a biomarker called phosphatidyl ethanol, which accumulates in the blood after alcohol consumption. The levels of this biomarker dropped markedly in the semaglutide group, directly aligning with their claims of reduced drinking. The placebo group did not show a statistically significant change in this biological marker.

The scientists also tracked changes using the World Health Organization’s risk drinking levels. This metric categorizes alcohol consumption into low, medium, high, and very high risk tiers. Moving down just two levels on this scale is associated with a lower chance of long-term health problems. The semaglutide group successfully achieved a two-level reduction much more frequently than the placebo group.

The medication also improved several physical health indicators. Patients taking semaglutide lost an average of 11.2 kilograms, which is roughly 24 pounds. The placebo group lost an average of only 2.2 kilograms, or about five pounds. The active treatment group also saw a measurable reduction in waist size and lowered blood pressure.

Doctors closely monitored the patients’ internal organs throughout the trial to ensure safety. They found that an enzyme linked to liver damage decreased sharply in the semaglutide group. However, levels of a digestive enzyme called amylase rose slightly in some patients receiving the active drug. Fortunately, these mild enzyme elevations did not cause symptoms or lead to serious pancreatic issues.

To evaluate the real-world usefulness of the drug, the researchers calculated a clinical metric known as the number needed to treat. This number represents how many patients must receive a medication for one person to achieve a highly positive outcome. For semaglutide in this specific study, the number needed to treat was 4.3.

This figure suggests a high level of pharmaceutical effectiveness. The currently approved medications for alcohol use disorder generally have a number needed to treat of seven or higher. “We’re beginning to see some of that potential for GLP-1s to treat drug addiction turn into reality. Questions remain but this is nonetheless very encouraging,” said Nora Volkow, a study co-author and director of the National Institute on Drug Abuse, in the National Institutes of Health press release.

The researchers did observe some adverse effects, though they were mostly related to the digestive system. Patients taking semaglutide frequently reported nausea, a loss of appetite, vomiting, and stomach pain. These side effects were generally mild to moderate and tended to pass quickly.

Despite the frequency of these gastrointestinal complaints, very few participants dropped out of the study because of them. Only four individuals in the semaglutide group discontinued the trial directly due to medication side effects. Overall, eighty-one percent of the enrolled participants completed the full 26-week intervention.

The medication’s benefits did not extend to all addictive behaviors tracked during the trial. Some participants were daily cigarette smokers at the start of the study. Despite the pronounced drop in their alcohol consumption, these individuals did not reduce their tobacco use. This observation suggests that the drug’s effects might vary depending on the specific substance involved.

While the trial provides strong evidence for the drug’s utility, the researchers and outside experts acknowledge several limitations. Because the study only included participants with a body mass index of thirty or higher, the results cannot automatically be applied to thinner individuals. It remains unknown if the medication would reduce alcohol cravings in patients who do not have comorbid obesity.

Additionally, the study was conducted at a single clinic with a relatively small sample size of 108 people. The participants were predominantly white, which limits how broadly the findings can be generalized to other demographic groups. The inclusion of cognitive behavioral therapy for all patients may have also boosted the overall success rates, masking how the drug might perform in a real-world setting without extensive therapy.

Perhaps the most pressing question involves what happens after the pharmacological treatment ends. The trial did not follow up with participants to monitor their alcohol consumption after the 26-week period concluded. Past research shows that when patients stop taking semaglutide for weight loss, their appetite often returns in full force.

Matt Field, a professor of psychology at the University of Sheffield who was not involved in the research, highlighted this unknown factor. “Drugs such as Ozempic and Wegovy act like brakes on our appetite. When people stop taking them, they are essentially taking their foot off the brake,” Field said in a statement provided to the Science Media Centre. He noted that a similar rebound effect might occur with alcohol consumption once the medication is stopped.

Moving forward, the authors plan to explore these lingering scientific questions. They hope to conduct larger trials that encompass diverse populations, including patients without obesity. Extended follow-up periods will also be necessary to determine if the medication can support long-term recovery from alcohol use disorder.

The study, “Once-weekly semaglutide versus placebo in patients with alcohol use disorder and comorbid obesity: a randomised, double-blind, placebo-controlled trial,” was authored by Mette Kruse Klausen, Signe Keller Justesen, Julie Niemann Pedersen, Line Rasmussen, Andreas Jensen, Mathias Ebbesen Jensen, et al.