GLP-1s For Treatment of Alcohol Use Disorder: Current and Future Directions

CONFERENCE REPORTER

At the annual meeting of the American Psychiatric Association (APA), held May 16–20 in San Francisco, California, Joji Suzuki, MD, shared research and psychiatric implications of the emerging role of glucagon-like peptide-1 (GLP-1) receptor agonists in the treatment of substance use disorders (SUDs).¹ Suzuki reviewed the science behind these agents, the current clinical trial landscape, and their potential to reshape addiction medicine.

From Gila Monster Venom to FDA Approval

Suzuki first recapped the origins of GLP-1 pharmacotherapy as an unexpected discovery in reptile venom when researching diabetes treatments. Researchers studying novel therapeutics for diabetes identified a peptide called exendin-4 in the venom of the Gila monster. This compound showed about 53% homology to human GLP-1 but had a half-life of approximately 2.4 hours compared with a few minutes in the native peptide.² The lengthened half-life made once-daily injection feasible and laid the foundation for subsequent GLP-1 receptor agonists. Exenatide, derived from exendin-4, became the first US Food and Drug Administration-approved agent in the class in 2005.³

Since the first approval, semaglutide (approved in 2017) represented a major leap in efficacy and tolerability. Tirzepatide, a dual agonist targeting both the GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors, followed with indication approvals in 2022 and 2023.⁴ Most recently, retatrutide has emerged as the first triple agonist, targeting GLP-1, GIP, and glucagon receptors simultaneously, with weight loss approaching 25% at 1 year—comparable to bariatric surgery outcomes, Suzuki pointed out.⁵

Substance Use Disorder: Clinical Trial Evidence

Suzuki reviewed a growing body of population-level data suggesting that patients on semaglutide experience meaningful reductions in alcohol use disorder (AUD)-related hospitalizations, incident and recurrent AUD diagnoses, and opioid-related overdose events. Preclinical models have shown reduced self-administration of alcohol, cocaine, fentanyl, heroin, and tobacco following GLP-1 receptor agonist exposure.⁶

A key development, Suzuki pointed out, is a recently published randomized controlled trial examining once-weekly semaglutide injection vs placebo in patients with AUD.⁷ This study adds to a previously quite limited evidence base: only 4 human clinical trials had been completed, 3 of which had negative primary outcomes.

On the opioid use disorder (OUD) front, Suzuki discussed brenipatide, a GLP-1–based investigational agent.⁸ If approved in the future for OUD, brenipatide would be the first new pharmacotherapy for that indication since buprenorphine—approved more than 20 years ago—which Suzuki underscored given the ongoing unmet need in OUD.

Investigation Into Combination Approaches, Drug-Drug Interactions

Suzuki listed active trials evaluating oral semaglutide in combination with established SUD pharmacotherapies such as naltrexone, reflecting growing interest in multimodal treatment strategies.⁹ These studies are investigating pairing GLP-1 agents with evidence-based treatments to potentially augment patient outcomes.

Suzuki also cautioned about potential for drug-drug interactions and some instances of pharmacokinetic effects. Because GLP-1 receptor agonists delay gastric emptying and alter absorption kinetics, they can affect the time to maximum concentration and peak concentration of concomitant medications. Suzuki specifically noted lithium, commonly used in bipolar disorder, as an example of an agent where altered pharmacokinetics may have clinical relevance and warrant monitoring.

Practical Implications

Suzuki framed developments in the neurobiology of addiction, noting that GLP-1 agents appear to attenuate the wanting, craving, and pleasure experience associated with both food and substances of abuse, potentially interrupting core reinforcement cycles that drive compulsive use. While clinical evidence continues to accumulate, the convergence of mechanistic plausibility, epidemiologic signal, and futures of trial data frames GLP-1 receptor agonists with potential in addiction pharmacotherapy.

References

1. Suzuki J. Injecting Hope: GLP-1 Receptor Agonists as Treatment for Substance Use Disorders. Conference Proceedings of the American Psychiatric Association Annual Meeting. May 2026;16-20. San Francisco, CA.

2. Ding X, Saxena NK, Lin S, et al. Exendin-4, a glucagon-like protein-1 (GLP-1) receptor agonist, reverses hepatic steatosis in ob/ob mice. Hepatology. 2006;43(1):173-81.

3. Byetta (exenatide) injection label. US Food and Drug Administration. 2005. Accessed May 16, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021773s9s11s18s22s25lbl.pdf

4. FDA approves new medication for chronic weight management. Press release. November 8, 2023. Accessed May 16, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-new-medication-chronic-weight-management

5. Jastreboff AM, Kaplan LM, Frias JP, et al. Triple-hormone-receptor agonist retatrutide for obesity—a phase 2 trial. N Engl J Med. 2023;389:514-526.

6. Loften A, Farokhnia M, Vendruscolo LF, et al. Neuroendocrinology meets addiction: emerging pharmacotherapies on the horizon. J Int Med. 2025;298(5):392-423.

7. Klausen MK, Justesen SK, Pedersen JN, et al. Once-weekly semaglutide versus placebo in patients with alcohol use disorder and comorbid obesity: a randomised, double-blind, placebo-controlled trial. Lancet. 2026;407(10540):1687-1698.

8. A study of brenipatide in participants with opioid use disorder (RENEW-Op-1). ClinicalTrials.gov. May 15, 2026. Accessed May 16, 2026. https://clinicaltrials.gov/study/NCT07420283

9. Combination therapy for alcohol use disorder. ClinicalTrials.gov. May 12, 2026. Accessed May 16, 2026. https://clinicaltrials.gov/study/NCT07249554