# 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. An earlier exenatide RCT failed on its primary endpoint in the overall sample but found significant reductions in heavy drinking days and total intake in a pre-specified obese subgroup (BMI >30), with a paradoxical increase in heavy drinking among lean participants, indicating that obesity may be a critical moderator of treatment response. Six large observational studies consistently report that GLP-1 RA use is associated with 28–75% lower rates of alcohol-related hospitalizations, alcohol intoxication events, and AUD diagnoses across populations with T2D or obesity, with stronger associations in more severe AUD and reductions in hepatic decompensation in those with alcohol-associated liver disease. Gastrointestinal adverse events are the primary safety signal, occurring more frequently with GLP-1 RAs than placebo; no pancreatitis or gallbladder events were observed, and available data do not suggest increased suicidality risk. Overall, the evidence supports the efficacy of semaglutide in reducing alcohol consumption and craving in adults with AUD and obesity, while evidence for benefit in AUD populations without obesity remains insufficient.

# 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. More on methods

## Paper search

### Elicit Corpus

We performed a semantic search across over 138 million academic papers from the Elicit search engine, which includes all of [Semantic Scholar](https://www.semanticscholar.org/) and [OpenAlex](https://openalex.org/).

### PubMed Corpus

We performed a keyword search across the [PubMed](https://pubmed.ncbi.nlm.nih.gov/) corpus.

## 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 using retrospective cohort, case-control, or target trial emulation designs. The studies span multiple countries and settings, with data windows ranging from 2005 to 2025.

| 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; diabetes excluded      | 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 (62 exenatide, 65 placebo); mean age 52 y; 40% female; diabetes excluded  | Low (RoB2)     |
| Lähteenvuo et al., 2024      | Yes                  | Register-based cohort (within-individual design) | Sweden; national registry | 2006–2021, follow-up to Dec 2023 | Exenatide, liraglutide, dulaglutide, semaglutide; dose/duration not specified | Non-use of GLP-1 agonists; also AUD medications | ICD-10 F10 AUD; N=227,886 (6,276 GLP-1 exposed); mean age 40.0 y; 36.5% female | Not formally assessed|
| Wang et al., 2024            | Yes                  | Retrospective cohort | United States; TriNetX EHR platform            | Dec 2017 – Dec 2022  | Semaglutide (2.4 mg Wegovy or 0.5–1 mg Ozempic); 12 months | Other anti-obesity or anti-diabetes medications | ICD-10 F10 AUD; 83,825 obesity / 598,803 T2DM; mean age 51.2 y; 65.9% female   | High (ROBINS-I) |

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 (d = 0.57), total alcohol grams consumed per 30 days (d = 0.54), and drinks per drinking day (d = 0.45).

## Effects

### Drinking Outcomes

| Study                         | Outcome                  | Effect Estimate (GLP-1 RA vs. Comparator) | 95% CI                 | p-value   | Notes                          |
|-------------------------------|-------------------------|-------------------------------------------|-----------------------|-----------|--------------------------------|
| Hendershot et al., 2025      | Drinks per drinking day  | beta = −0.41                              | −0.73 to −0.09       | 0.04      | Significant reduction           |
| Hendershot et al., 2025      | Heavy drinking days (IRR)| IRR = 0.84                                | 0.71 to 0.99          | 0.04      | Significant reduction           |
| Hendershot et al., 2025      | Total alcohol grams (lab session) | beta = −0.48               | −0.85 to −0.11      | 0.01      | Significant reduction           |

### 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     |

### Biomarkers

| Study                         | Biomarker                | Direction and Magnitude                     | 95% CI                  | p-value   |
|-------------------------------|--------------------------|---------------------------------------------|------------------------|-----------|
| Jensen et al., 2025          | PEth                     | −0.9 micromol/L (exenatide vs. placebo, Week 26)  | −1.6 to −0.1          | 0.03      |
| Klausen et al., 2026        | PEth                     | −0.28 micromol/L treatment difference         | −0.41 to −0.15        | <0.0001   |

### Alcohol-Related Harms

| Study                         | Outcome                  | Effect Estimate                             | 95% CI                 | Population                                   |
|-------------------------------|-------------------------|--------------------------------------------|------------------------|---------------------------------------------|
| Lähteenvuo et al., 2024      | AUD hospitalization (semaglutide) | aHR = 0.64                               | 0.50–0.83             | AUD, Sweden registry                         |
| Rodriguez et al., 2025       | Alcohol-related hospitalization (ADM trial) | HR = 0.70                     | 0.59–0.83             | AUD + T2D                             |

### Safety

| Study                         | Any AE (GLP-1 RA arm) | Any SAE (GLP-1 RA arm) | GI AEs (Nausea) | Pancreatitis | Suicidality | Discontinuation Overall | Discontinuation due to AEs   |
|-------------------------------|----------------------|-----------------------|----------------|--------------|-------------|------------------------|--------------------------|
| Hendershot et al., 2025      | Not reported          | Not reported           | Not reported    | Not reported  | Not reported  | Not reported             | Not reported              |
| Klausen et al., 2022        | Nausea 37.1%, vomiting 22.6%   | 24.2% (exenatide) vs 18.5% (placebo) | Nausea 37.1% vs 15.4%   | 0 cases      | 1 suicide (exenatide, post-withdrawal) | 54.3%               | ≥6.5% (injection site reactions)   |

## Synthesis

The evidence supports that 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, total alcohol grams, and craving. For individuals with AUD but without obesity, the evidence is insufficient to conclude benefit. GLP-1 RAs appear well-tolerated in AUD populations, with gastrointestinal adverse events as the primary safety signal, no observed pancreatitis, and no evidence of increased suicidality.