Anecdotal reports have circulated for years: people taking Ozempic or Wegovy found themselves drinking less alcohol without really trying. Now, we have the first placebo-controlled randomized trial confirming this effect.
Published in JAMA Psychiatry in February 2025, the study by Hendershot et al. provides initial prospective evidence that low-dose semaglutide reduces alcohol consumption and cravings in adults with alcohol use disorder.
Study Design
This phase 2 trial was designed to test whether the effects seen in animal studies and anecdotal human reports would hold up in a controlled setting.
| Design | Phase 2, double-blind, randomized, placebo-controlled |
| Participants | 48 adults with alcohol use disorder (AUD) |
| Key characteristic | Not actively seeking treatment for AUD |
| Duration | 9 weeks of treatment + 1-week follow-up |
| Dosing | 0.25 mg (weeks 1-4) → 0.5 mg (weeks 5-8) → 1.0 mg (week 9) |
| Setting | University of North Carolina, Chapel Hill |
| Lead investigators | Christian Hendershot, PhD (USC/UNC) and Klara Klein, MD, PhD (UNC) |
A unique feature of this trial: participants came to a lab designed like a living room (complete with a TV playing National Geographic) and were free to drink their preferred alcoholic beverage over 2 hours. This allowed objective measurement of actual alcohol consumption, not just self-reports.
Primary Outcome: Lab Alcohol Consumption
The primary endpoint was alcohol self-administration measured in a controlled laboratory setting before treatment and after reaching the 0.5 mg dose (between weeks 8-9).
| Measure | Effect Size (β) | P-value | Interpretation |
|---|---|---|---|
| Grams of alcohol consumed | -0.48 | 0.01 | Medium-large effect |
| Peak breath alcohol concentration | -0.46 | 0.03 | Medium-large effect |
In the post-treatment lab session, participants on semaglutide drank approximately 40% less alcohol than those on placebo.
Secondary Outcomes: Weekly Drinking Patterns
Over the 9-week treatment period, weekly assessments revealed:
| Outcome | Effect | P-value |
|---|---|---|
| Drinks per drinking day | Significantly reduced (β = -0.41) | 0.04 |
| Weekly alcohol craving | Significantly reduced (β = -0.39) | 0.01 |
| Heavy drinking days | Greater reductions over time vs. placebo | 0.04 |
| Average drinks per calendar day | No significant difference | NS |
| Number of drinking days | No significant difference | NS |
The nuance is important: semaglutide didn't change how often people drank, but it reduced how much they drank when they did drink—and reduced their cravings.
Bonus Finding: Cigarette Reduction
Among the 13 participants who smoked cigarettes at baseline, those on semaglutide showed significantly greater reductions in cigarettes per day compared to placebo (β = -0.10; P = 0.005). This suggests potential dual benefits for people struggling with both alcohol and nicotine.
Safety and Tolerability
| Safety Metric | Result |
|---|---|
| Mean weight loss (semaglutide group) | 5% |
| Serious adverse events | None |
| Discontinuations due to treatment | None |
| Most common side effects | Mild GI symptoms (as expected) |
The treatment was well-tolerated, even in a population with active alcohol use disorder.
How Does This Compare to Existing AUD Medications?
Three medications are FDA-approved for alcohol use disorder: naltrexone, acamprosate, and disulfiram. However, they're underutilized.
Dr. Hendershot noted that naltrexone, one of the most commonly used AUD medications, shows a "small effect size" in clinical trials. The semaglutide trial showed effect sizes "in the medium to large range"—though he urged caution given the small sample size.
An estimated 178,000 U.S. deaths per year are attributable to alcohol, which is linked to liver disease, cardiovascular disease, and cancer (as recently highlighted by the U.S. Surgeon General). Yet only a small fraction of people with AUD receive any treatment. The popularity and mainstream acceptance of GLP-1 medications could potentially change this—if they prove effective in larger trials.
Mechanistic Hypothesis
Why would a diabetes/weight loss drug reduce alcohol consumption?
GLP-1 receptors are found throughout the brain's reward circuitry—the same dopaminergic pathways involved in addiction. Preclinical research suggests GLP-1 receptor activation reduces the rewarding effects of addictive substances including alcohol.
Dr. Klein explained: "Research is needed to understand the mechanisms by which GLP-1 receptor agonists reduce alcohol cravings. Preclinical studies suggest that these effects are likely mediated in the brain and involve changes in reward processing."
Study Limitations
The researchers acknowledged several important limitations:
- Small sample size (48 participants)—typical for phase 2 but limits generalizability
- Short duration (9 weeks)—we don't know about long-term effects
- Low doses only—didn't reach the 2.4 mg maximum used for weight loss
- Moderate AUD severity—may not apply to severe cases
- Non-treatment-seeking—participants weren't trying to quit drinking
"These data suggest the potential of semaglutide and similar drugs to fill an unmet need for the treatment of alcohol use disorder. Larger and longer studies in broader populations are needed to fully understand the safety and efficacy." — Dr. Klara Klein
What Comes Next
This trial justifies larger phase 3 trials. The VA is currently running the CRAVE trial (NCT06320171), a much larger study testing semaglutide for AUD in veterans.
Key questions for future research:
- What is the optimal dose for AUD treatment?
- Do effects persist with continued treatment?
- What happens after stopping—does drinking return to baseline?
- How does semaglutide compare head-to-head with existing AUD medications?
- Would combination therapy (semaglutide + existing AUD meds) be more effective?
Expert Reactions
The study received cautious optimism from the scientific community:
This JAMA Psychiatry study provides the first randomized, placebo-controlled evidence that semaglutide reduces alcohol consumption and cravings in adults with alcohol use disorder. Participants on low-dose semaglutide drank about 40% less in lab settings, showed reduced cravings, and had fewer heavy drinking days. The study was small (48 participants) and short (9 weeks), so these findings need confirmation in larger trials before clinical recommendations can change. However, given the massive unmet need for AUD treatment and semaglutide's widespread use, these results are highly significant and justify further investigation. No GLP-1 medication is currently approved for alcohol use disorder.
Sources
- Hendershot CS, et al. "Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A Randomized Clinical Trial." JAMA Psychiatry. 2025;82(4):395-405.
- UNC Health Newsroom. "Semaglutide Shows Promise in Reducing Cravings for Alcohol, Heavy Drinking." February 2025.
- USC Today. "Popular weight-loss, diabetes drug shows promise in reducing cravings for alcohol." February 2025.
- CNN. "Ozempic shown to reduce drinking in first trial in alcohol-use disorder." February 2025.
- Brain & Behavior Research Foundation. "GLP-1 Drug Semaglutide Reduced Heavy Drinking & Craving in Adults with Alcohol Use Disorder." July 2025.
- Science Media Centre. "Expert reaction to study looking at once-weekly semaglutide in adults with alcohol use disorder." February 2025.
- NEI Global. "Once-Weekly Semaglutide in Adults With Alcohol Use Disorder." 2025.
- ClinicalTrials.gov. NCT05520775.
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