Elicit: GLP-1 receptor agonists for efficacy and safety in adults with alcohol use disorder: a joint synthesis of consumption, alcohol-related harms, and adverse events
GLP-1 receptor agonists for efficacy and safety in adults with alcohol use disorder: a joint synthesis of consumption, alcohol-related harms, and adverse events
What is the evidence for the efficacy and safety of GLP-1 receptor agonists in reducing alcohol consumption and alcohol-related harms in adults with alcohol use disorder?
RCT evidence demonstrates that semaglutide significantly reduces alcohol consumption, craving, and objective drinking biomarkers in adults with co-occurring AUD and obesity, while large observational studies consistently show GLP-1 RA use is associated with substantially lower rates of alcohol-related hospitalizations and diagnoses, with gastrointestinal side effects as the main safety concern and no signal for pancreatitis or suicidality; however, evidence for efficacy in individuals with AUD who do not have obesity is currently insufficient, and one trial suggested potential harm in lean participants.
Abstract
Ten studies—four RCTs and six observational studies—examine the efficacy and safety of GLP-1 receptor agonists in adults with AUD. The strongest trial evidence comes from a 26-week RCT of semaglutide 2.4 mg weekly in adults with AUD and co-occurring obesity, which demonstrated significant reductions in heavy drinking days (−13.7 percentage points vs. placebo; Cohen’s d = 0.57), total alcohol consumption (−467.5 g/30 days), craving (PACS −3.3 points; p = 0.0024), and the objective biomarker PEth (p < 0.0001). A phase 2 trial of low-dose semaglutide over 9 weeks similarly showed significant reductions in alcohol self-administration and craving.
Methods
We analyzed 10 sources from an initial pool of 7469, using 4 screening criteria. Each paper was reviewed for 17 key aspects that mattered most to the research question.
Paper search
Elicit Corpus
We performed a semantic search across over 138 million academic papers from the Elicit search engine.
Screening
We screened in sources based on their abstracts that met strict criteria for human studies, GLP-1 RA intervention, alcohol outcomes, and empirical data.
10 papers passed full-text screening and moved to data extraction.
Results
Characteristics of Included Studies
The review identified 10 studies examining GLP-1 receptor agonists (GLP-1 RAs) in adults with alcohol use disorder (AUD). These comprised four randomized controlled trials (RCTs) or secondary analyses thereof, and six observational studies.
| Study | Full text retrieved? | Study Design | Country and Setting | Data Window | GLP-1 RA (Drug, Dose, Duration) | Comparator | Population (AUD Definition, N, Mean Age, % Female, Key Comorbidities) | Risk of Bias |
|---|---|---|---|---|---|---|---|---|
| Hendershot et al., 2025 | Yes | RCT (phase 2) | United States; university research setting | Sep 2022 – Feb 2024 | Semaglutide SC, 0.25 mg (wk 1–4), 0.5 mg (wk 5–8), 1.0 mg (wk 9); 9 weeks | Placebo | DSM-5 AUD; N=48; mean age 39.9 y; 71% female; obesity prevalent | Low (RoB2) |
| Klausen et al., 2022 | Yes | RCT | Denmark; specialist addiction outpatient clinics | Aug 2017 – Oct 2019 | Exenatide SC 2 mg once weekly; 26 weeks | Placebo | DSM-5/ICD-10 AUD; N=127; mean age 52 y; 40% female | Low (RoB2) |
| Jensen et al., 2025 | Yes | Secondary analysis of RCT | Not specified | Not specified | Exenatide extended-release SC once weekly; 26 weeks | Placebo | AUD + obesity; N=30; mean age 53 y; 30% female | Some concerns (RoB2) |
| Klausen et al., 2026 | Yes | RCT (single-centre) | Denmark; specialist outpatient mental health/addiction service | Jun 2023 – Feb 2025 | Semaglutide (Wegovy) SC, 0.25–2.4 mg weekly; 26 weeks | Placebo | DSM-5/ICD-10 AUD + obesity; N=108; mean age 52.3 y; 49% female | Low (RoB2) |
All 10 studies had full texts retrieved.
Effects
Drinking Outcomes
| Study | Outcome | Effect Estimate (GLP-1 RA vs. Comparator) | 95% CI | p-value |
|---|---|---|---|---|
| Hendershot et al., 2025 | Drinks per drinking day | beta = −0.41 | −0.73 to −0.09 | 0.04 |
| Klausen et al., 2022 | Heavy drinking days (BMI >30 subgroup) | −23.6 percentage points | −44.4 to −2.7 | 0.034 |
The strongest trial-level evidence for efficacy on drinking outcomes comes from the Klausen et al. (2026) RCT. This trial demonstrated clinically meaningful reductions in heavy drinking days and total alcohol grams consumed.
Craving
| Study | Measure | Effect Estimate | 95% CI | p-value |
|---|---|---|---|---|
| Hendershot et al., 2025 | PACS | beta = −0.39 | −0.73 to −0.06 | 0.01 |
| Klausen et al., 2026 | PACS | −3.3 points | −5.5 to −1.2 | 0.0024 |
Two of three RCTs reporting craving demonstrated significant reductions.
Alcohol-Related Harms
Safety
Safety data are available primarily from the RCTs. Gastrointestinal adverse events were the most frequently reported class. No cases of pancreatitis were reported in any trial.
Synthesis
In adults with co-occurring AUD and obesity, semaglutide at doses of 2.4 mg weekly for 26 weeks produces clinically meaningful reductions in heavy drinking days, alcohol consumption, and craving. For individuals with AUD but without obesity, the evidence is insufficient, and one trial suggested potential harm in lean individuals.
References
- Hendershot, C.S., Bremmer, M.P., Paladino, M.B., et al. (2025). Once-Weekly Semaglutide in Adults With Alcohol Use Disorder. JAMA Psychiatry.
- Klausen, M.K., Jensen, M.E., Møller, M., et al. (2022). Exenatide once weekly for alcohol use disorder investigated in a randomized, placebo-controlled clinical trial. JCI Insight.
- Lähteenvuo, M., Tiihonen, J., Solismaa, A., et al. (2024). Repurposing Semaglutide and Liraglutide for Alcohol Use Disorder. JAMA Psychiatry.