Status Of GLP-1 drugs and their application in treating substance use disorders: A systematic review

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have an exciting future potential beyond metabolic disorders. This review gauges their effectiveness, safety, and clinical role in the management of substance use disorders in diverse populations.

A PRISMA-guided systematic review searched PubMed, Scopus, WoS, CENTRAL and PsycINFO up to March 2026; 1641 records were identified, 11 included; screening, extracting and evaluating the efficacy, safety, and bias of the studies.

11 studies were selected out of 1641 records. Reduced substance-related outcomes were always observed with GLP-1RAs. In alcohol use disorder (AUD), there was a decrease in the risk of hospitalization (aHR 0.640.72), and reduced incident AUD (OR 0.260.71), but randomized controlled trials (RCTs) provided contradictory outcomes (p = 0.37; 29% reduction, p = 0.04). Semaglutide reduced the risk of tobacco use disorder (HR 0.68; 95% CI 0.630.74). There was a great decrease in the risk of opioid overdose (HR 0.32-0.58). The incidence (HR 0.86), mortality (HR 0.50), and suicidal ideation were less in composite substance use disorder (SUD) outcomes (HR 0.75). Weight reduction was consistent (-2.9 kg; ≥16 kg in 37.5%), with HbA1c improvements (-0.25%). RCTs were found to be low-bias and the observational studies were moderate-bias. The safety profiles were positive, and there were no patterns of increasing serious adverse events (SAEs).

GLP-1RAs have good potential protective properties against SUD especially in observational research with good safety. However, robust randomized trials are needed to confirm causality and clinical applicability.