GLP1 Agonists Show Promise for Treating Substance Use Disorders

Glucagon-like peptide 1 receptor agonists (GLP1RAs) have been shown to be effective for type II diabetes mellitus and obesity; there is increasing interest in their potential as treatments for substance use disorders. Two recently published studies have investigated this further.

Qeadan et al conducted an observational study using data from 136 US health care systems and included patients with a documented history of opioid or alcohol use disorder (OUD or AUD). They compared rates of encounters for opioid overdose and alcohol intoxication among people who had been prescribed a GLP1RA medication with those who had not.

• There were 817,000 participants with AUD and 504,000 with OUD; 13,725 (1 percent) had received a GLP1RA. Those who received GLP1RAs had lower baseline rates of opioid overdose and alcohol intoxication.
• Among individuals who received a GLP1RA, those with OUD had a 40 percent lower adjusted rate of opioid overdose, and those with AUD had a 50 percent lower rate of alcohol intoxication, compared with those not receiving a GLP1RA. Moreover, the rates of both overdose and alcohol intoxication declined after receiving the first GLP1RA prescription; these rates also declined among those who did not receive a GLP1RA, but to a lesser extent.

Hendershot et al conducted a clinical trial that included 48 adults aged 21–65 with AUD and body mass index (BMI) of ≥23. Participants were randomized to placebo or semaglutide (0.25 mg per week for weeks 1–4, 0.5 mg for weeks 5–8, and a final dose of 1 mg at week 9, if tolerated). The participants were 71 percent female, the mean age was 40, and most (56 percent) had a BMI >30.

• In laboratory alcohol self-administration testing, semaglutide reduced post-treatment alcohol consumption and peak alcohol breath concentration.
• Participants who received semaglutide had a significant decline in drinks per drinking days and heavy drinking days, but not drinks per calendar days or number of days abstinent; they also had reduced weekly craving.

Comments: These studies suggest that GLP1RA medications are a promising treatment for substance use disorders and an attractive option for those with comorbid diabetes or obesity. At this time, cost is a major barrier; we also need to learn more about long-term efficacy and impact on clinical outcomes.

Darius A. Rastegar, MD

References: Qeadan F, McCunn A, Tingey B. The association between glucose-dependent insulinotropic polypeptide and/or glucagon-like peptide-1 receptor agonist prescriptions and substance-related outcomes in patients with opioid and alcohol use disorders: A real-world data analysis. Addiction. 2025;120(2):236–250.

Hendershot CS, Bremmer MP, Paladino MB, et al. Once-weekly semaglutide in adults with alcohol use disorder: a randomized clinical trial. JAMA Psychiatry. 2025;82(4):395–405.