Summary: In a randomized clinical trial, oral semaglutide significantly reduced heavy drinking days, daily alcohol cravings, and alcohol-related problems in adults with moderate-to-severe Alcohol Use Disorder (AUD).
Researchers evaluated 50 adults seeking treatment for AUD and found that oral semaglutide—a glucagon-like peptide-1 (GLP-1) receptor agonist already prescribed for type 2 diabetes and chronic weight management—consistently reduced real-world heavy drinking and lowered days of cannabis use. These results point to oral semaglutide as a promising, non-injectable treatment candidate for AUD that can reduce alcohol-related harm even when patients are not aiming for complete abstinence.
Key Facts
- First double-blind evidence for oral GLP-1 in AUD: While earlier research focused on injectable GLP-1 medications, this trial provides the first randomized, double-blind clinical evidence that an oral GLP-1 agonist can lower harmful alcohol intake in treatment-seeking adults.
- Reduced heavy drinking and per-occasion consumption: Participants taking oral semaglutide experienced significantly fewer heavy drinking days and drank less per drinking episode during the eight-week intervention.
- Lower cravings and fewer alcohol-related problems: Treatment decreased day-to-day alcohol cravings, improved World Health Organization drinking risk levels, and reduced self-reported social and health consequences of drinking.
- Impact on co-occurring substance use: The semaglutide group also showed a reduction in cannabis use days over the study period.
- Feasibility and safety: Oral semaglutide was generally well tolerated, produced mostly mild side effects, and demonstrated high adherence and retention consistent with practical outpatient use.
Source: University of Colorado
A clinical trial led by investigators at CU Anschutz found that oral semaglutide reduces heavy drinking in adults with Alcohol Use Disorder.
Published in The American Journal of Psychiatry, the study tested an oral formulation that may be more acceptable to people with AUD than injectable GLP-1 drugs previously studied. The convenience of a daily oral tablet could improve acceptability and adherence for many patients compared with weekly injections.
“This study suggests oral semaglutide may help reduce heavy and harmful drinking, even in people who are not trying to quit alcohol entirely,” said Joseph Schacht, PhD, associate professor at the CU Anschutz School of Medicine. He emphasized that even modest reductions in heavy drinking can produce meaningful improvements in health, safety, and family stability.
Why this matters for patients and families
Alcohol Use Disorder is a chronic medical condition that affects millions and can damage physical health, mental health, relationships, and safety. Treatment options remain limited, and no new medications for AUD have been approved in nearly two decades. A well-tolerated, oral medication that reduces heavy drinking could broaden treatment choices, help people who don’t respond to current medicines, and reduce alcohol-related harms in real-world settings.
Key potential benefits highlighted by the research include:
- Reducing harmful drinking without requiring complete abstinence
- Offering an additional therapeutic option for patients who do not benefit from existing medications
- Lowering the risk of alcohol-related physical, social, and safety problems
Trial design and key outcomes
This phase 2, double-blind, randomized, placebo-controlled trial enrolled 50 adults with moderate-to-severe AUD. Participants received oral semaglutide (3 mg/day for four weeks, then 7 mg/day for four weeks) or placebo for eight weeks. The primary laboratory outcome was alcohol cue–elicited craving at week 6. Pre-registered secondary outcomes included heavy drinking days and drinks per day during the final four weeks of treatment, as well as real-world craving, alcohol-related negative consequences, World Health Organization risk drinking level, and cannabis use.
Results
Although semaglutide did not significantly lower laboratory-assessed craving or overall drinks per day versus placebo, it produced several meaningful real-world improvements:
- Significant reduction in heavy drinking days
- Fewer drinks per drinking day
- Lower naturalistic (day-to-day) alcohol craving
- Fewer alcohol-related social and health consequences
- Reduced days of cannabis use
- More participants moved down at least one WHO drinking risk level compared with placebo
Safety and next steps
Oral semaglutide was generally well tolerated; most adverse effects were mild. High study completion and adherence rates suggest feasibility in outpatient settings. Investigators emphasize the need for larger, longer-term trials to confirm these findings, refine dosing strategies, and evaluate long-term safety and effectiveness before seeking regulatory approval for AUD.
Funding: The study received partial funding from the National Institute on Alcohol Abuse and Alcoholism.
Key questions answered
Q: Why is an oral formulation important?
A: Oral semaglutide offers a needle-free daily option that may be more acceptable and less stigmatizing for many people with AUD, improving adherence and integration into primary care.
Q: Does a patient need to commit to complete abstinence for semaglutide to be helpful?
A: No. The trial showed reductions in heavy drinking and per-occasion consumption among participants who were not aiming for total abstinence, which can still reduce risks of liver disease, cardiovascular events, injury, and social harms.
Q: Is semaglutide FDA-approved for AUD?
A: Not at this time. Semaglutide is approved for type 2 diabetes and chronic weight management, but its use for AUD remains investigational and requires larger phase 3 trials for regulatory consideration.
About this research
Author: Laura Kelley
Source: University of Colorado Anschutz
Contact: Laura Kelley – University of Colorado Anschutz
Image credit: Neuroscience News
Original research (open access): “Oral Semaglutide for Alcohol Use Disorder: A Randomized Clinical Trial” by Joseph P. Schacht et al., American Journal of Psychiatry. DOI: 10.1176/appi.ajp.20260003
Abstract
Objective: Preclinical and observational data suggest GLP-1 receptor agonists can reduce alcohol intake. This phase 2 double-blind randomized trial tested oral semaglutide’s effects on craving and consumption among treatment-seeking adults with AUD.
Methods: Fifty adults with moderate-to-severe AUD were randomized to semaglutide (3 mg/day for four weeks, then 7 mg/day for four weeks) or placebo for eight weeks. Primary outcome: cue-elicited craving at week 6. Secondary outcomes: heavy drinking days and drinks per day during the final four weeks, plus additional measures of craving, alcohol-related consequences, WHO risk level, and cannabis use.
Results: Semaglutide significantly reduced heavy drinking days, drinks per drinking day, naturalistic craving, alcohol-related consequences, and cannabis use days, and more participants lowered their WHO risk drinking level compared to placebo. Laboratory cue-induced craving and drinks per day did not differ significantly.
Conclusions: These results align with prior findings in less severe, non–treatment-seeking samples and support further clinical development of semaglutide as a potential treatment for Alcohol Use Disorder.