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.

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 and OpenAlex.

We ran these queries:

• "GLP-1 receptor agonists for alcohol use disorder efficacy and safety"
• "GLP-1 receptor agonist alcohol-related harms hepatic hospitalization adverse events mortality"

The searches returned 10,000 total results from Elicit.

PubMed Corpus

We performed a keyword search across the PubMed corpus.

We ran this query: (semaglutide[tiab] OR liraglutide[tiab] OR exenatide[tiab] OR dulaglutide[tiab] OR tirzepatide[tiab] OR "GLP-1 receptor agonist"[tiab] OR "glucagon-like peptide-1 receptor agonist"[tiab]) AND ("alcohol use disorder"[tiab] OR "alcohol dependence"[tiab] OR "alcohol consumption"[tiab] OR "alcohol craving"[tiab] OR "alcohol drinking"[tiab] OR alcoholism[tiab] OR "heavy drinking"[tiab]) NOT (steatohepatitis[tiab] OR NAFLD[tiab] OR NASH[tiab] OR MASH[tiab] OR MASLD[tiab])

The search returned 96 total results from PubMed.

Screening

Abstract screening

We screened in sources based on their abstracts that met these criteria:

• Human study: The study is conducted in humans.
• GLP-1 RA intervention: The study evaluates a GLP-1 receptor agonist (semaglutide, liraglutide, exenatide, dulaglutide, lixisenatide, albiglutide) or a dual/triple agonist with a GLP-1 component (tirzepatide, retatrutide, pemvidutide, cagrilintide+semaglutide).
• Alcohol outcome: The study reports at least one alcohol-related outcome: alcohol consumption (drinks, AUDIT, %DA, heavy drinking days), craving, AUD diagnosis or symptoms, alcohol-related hospitalization or ED visit, alcohol-related liver disease progression, or alcohol-related mortality.
• Empirical data: The article reports primary empirical data (RCT, cohort, case-control, register study, target trial emulation, pharmacovigilance, case series with n>=10).

At abstract screening, 61 papers passed and moved to full-text screening.

Data extraction

We asked a large language model to extract data columns from each paper, including study design, country and setting, recruitment/data window, population, GLP-1 RA details, comparator, outcomes, safety signals, and risk of bias.

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) and six observational studies.

Effects

Drinking Outcomes

Safety

Overall, the gastrointestinal adverse events were the most frequently reported, occurring more commonly in GLP-1 RA arms than in placebo.

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. For individuals with AUD but without obesity, evidence is insufficient for benefit and suggests potential harm in lean individuals. In populations with T2D or obesity prescribed GLP-1 RAs, there is consistent reduction in alcohol-related hospitalizations.