A 2026 study published in The Lancet suggests that tirzepatide, a dual GLP-1 and GIP receptor agonist already approved for treatment of diabetes and obesity, could be an effective tool for fighting alcohol use disorder (AUD).
The work is being conducted as part of a National Institute on Alcohol Abuse and Alcoholism preclinical program, in which a small number of labs tested potential AUD medications in controlled animal models before advancing them to human trials.
“Semaglutide is strictly a GLP-1 receptor agonist. Tirzepatide is what’s called a dual agonist. It operates both on GLP-1 receptors and GIP receptors, which is a glucose-dependent insulinotropic polypeptide,” said Howard Becker, Ph.D., professor of neuroscience and psychiatry and director of the Charleston Alcohol Research Center.
“There were anecdotal reports that these drugs, which are principally used for the management of diabetes, were found to reduce appetite for alcohol, which led people to wonder if there is the potential for these medications to be useful for the treatment of alcohol use disorder and perhaps other substance use disorders,” he continued.
Becker and his team, including postdoctoral fellow and study coauthor Samantha Gottlieb, ran experiments to understand how the drug affects both behavior and brain activity. In collaboration with investigators at the University of Gothenburg (Sweden), they measured how strongly subjects associated alcohol with reward, how much they drank during binge-like episodes and whether drinking increased again after a period of abstinence. They also examined dopamine signaling to understand how tirzepatide influences the brain’s reward system.
They also assessed metabolic and inflammatory effects, including body weight, fat mass, liver fat and inflammatory markers. The goal was not just to see if tirzepatide reduces drinking but to understand how it works.
“It’s unclear how these drugs are actually producing this effect. And that’s what we have been interested in trying to go after. What is the mechanism by which these drugs might be changing motivation to drink?” Becker said.
Key findings
Tirzepatide consistently reduced alcohol consumption and dampened its pleasurable effects. It lowered behavioral responses and blocked dopamine release in the brain, even when alcohol was delivered directly to the reward center.
“There have been some reports that these GLP-1 agonists influence reward circuitry in the brain, and through influencing these reward circuits, they may blunt the rewarding effects of alcohol,” Becker said.
This translated into reductions in alcohol intake in both sexes, including lower voluntary drinking and a reduced preference for alcohol.
The drug also significantly reduced binge-like drinking, prevented relapse-like spikes after abstinence and decreased cue-driven alcohol seeking. These effects were sustained with repeated dosing. Researchers identified the lateral septum, a part of the brain that is involved in reward and motivation, as a potential hub.
“We have started to look at where in the brain these effects may be occurring so we can better understand how these drugs influence activity of specific brain regions that are thought to be involved in reward processing and chronic alcohol effects,” said Becker.
Beyond behavior, tirzepatide also improved the physical consequences of chronic alcohol use, reducing body weight, fat mass, liver triglycerides and inflammation, suggesting potential benefits for both addiction and metabolic health.
Why this matters
Becker explained that current medications for AUD are limited in effectiveness and underused in practice. Tirzepatide stands out, he said, because it is already FDA approved and widely used for diabetes and obesity, with established safety and prescribing practices in place. That lowers the barrier to testing it for alcohol dependence and increases the possibility of repurposing it for the treatment of alcohol use disorder.
What’s next
Becker said there are currently more than a dozen ongoing trials of GLP-1 dual agonists for alcohol use disorder, largely focused on whether these drugs reduce drinking and identifying which patients most benefit from this treatment strategy. But they don’t explain how the drugs work.
Becker’s lab is addressing that gap by mapping where these drugs act in the brain and how they influence reward and motivation circuits, including how signals from the gut may shape craving and behavior.
“We’re also looking at drugs that block these receptors to see whether the reduction in alcohol use is truly driven by GLP-1 receptors or by nonspecific ‘off-target’ effects involving other mechanisms,” noted Becker. That understanding may also explain why people often regain weight after discontinuing these medications, suggesting rebound effects and changes tied to the brain or gut.
Becker noted that controlled studies are important because they allow researchers to track how the brain responds over time – something that is difficult to measure in human clinical trials. Ultimately, this could lead to more targeted, effective treatments for AUD with fewer side effects.
“We want to find medications that will effectively reduce excessive, dangerous or risky drinking but not make someone not feel interested in eating chocolate cake or other pleasurable activities,” he said.
As April is designated National Alcohol Awareness Month, everyone should be thinking about their drinking habits, Becker said.
“Given the prevalence and scope of medical problems associated with prolonged heavy alcohol drinking, our work at the MUSC Charleston Alcohol Research Center is more important than ever.”