Rethinking Alcohol Use Disorder Through GLP-1 Agonism

February 19, 2026

Class Act Diseases 2.0 Pharmacology Psychiatry 6 min read

By Joshua Wang

Peer Reviewed

Dan never imagined his nightly struggle with alcohol cravings might be cured with his diabetes medication. Yet, a few months after starting semaglutide for his blood sugar, he found himself leaving unfinished beers on the table, a stark contrast to years of compulsive drinking. His friends joked that he had discovered a “sobriety shot,” but Dan’s experience reflects a growing scientific intrigue. Could drugs developed for diabetes and weight loss help treat alcohol use disorder (AUD)? In recent years, anecdotal reports like Dan’s have joined with developing research that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce alcohol craving and intake.

GLP-1 RAs like semaglutide and liraglutide have revolutionized the treatment of type 2 diabetes and obesity by enhancing insulin secretion, slowing gastric emptying, and reducing appetite. Semaglutide’s dramatic weight loss efficacy earned it headlines as a “game-changer” for obesity. But its effects extend beyond just the pancreas or gut. GLP-1 receptors are also expressed in the brain’s reward circuitry, including regions like the ventral tegmental area and nucleus accumbens that control motivation and pleasure. Preclinical studies suggest that activating these receptors can dampen dopamine-driven reward signals.1 This neurobiological crosstalk between metabolism and addiction opens the door to an intriguing hypothesis: could GLP-1 RAs be repurposed to treat substance use disorders, like AUD, by reducing the reinforcing effects of alcohol? 

The earliest tests of this hypothesis unfolded in animal labs. Semaglutide has been shown to significantly reduce voluntary alcohol intake and even prevented relapse-like drinking behavior in both male and female rats.2 Rats treated with semaglutide chose to drink less alcohol, which was attributed to semaglutide’s action on central GLP-1 receptors modulating dopamine and gamma-aminobutyric acid (GABA). GLP-1 RAs can also decrease intake of other drugs: exendin-4 (a shorter-acting GLP-1 agonist) reduced cocaine self-administration and amphetamine-induced dopamine release in mice,3 and liraglutide blunted nicotine use in rat models.4 Moreover, the GLP-1 effect appears specific. When researchers tried drugs that increase endogenous GLP-1, like DPP-4 inhibitors, they did not see the same reduction in alcohol consumption.5 This implies it’s the direct activation of GLP-1 receptors, rather than generalized improvements in diabetes or metabolism, driving the anti-addiction effect. Taken together, preclinical evidence suggests that GLP-1 RAs can alter the neurobiology of addiction in animals, reducing drug and alcohol rewards. 

Although not hard evidence, anecdotes from physicians and patients have aligned with the science thus far. In 2022, an analysis of Danish and Swedish health records concluded that patients on GLP-1 RAs had fewer alcohol-related hospital visits than those on other diabetes medications.6,7 Among 227,000 individuals with AUD in Sweden from 2006–2021, semaglutide use was associated with a 36% reduction in the risk of alcohol-related hospitalization, and liraglutide with a 28% reduction, compared to periods of no GLP-1 treatment.6 In fact, these risk reductions were greater than those seen with standard AUD medications like naltrexone, for example, which showed only about a 14% risk reduction in the same analysis. Notably, GLP-1 RA treatment in this study was also linked to fewer hospitalizations for any substance use disorder and for alcohol-related physical illnesses, suggesting a broader beneficial effect. 

Randomized Controlled Trials

Until recently, no large randomized controlled trial (RCT) had specifically tested GLP-1 RAs in patients with AUD. That changed with the first Phase II trial of semaglutide for AUD, where 48 adults with AUD were randomized to receive either loading-doses of semaglutide or placebo for 9 weeks, while tracking their alcohol intake and craving. The findings were encouraging: individuals treated with semaglutide had greater reductions in the number of heavy drinking days and overall alcohol consumption compared to those on placebo.8 Participants on semaglutide also reported less intense alcohol cravings, reminiscent of the medication’s known effect of reducing appetite for food. This RCT provides the first direct evidence in humans that GLP-1 RAs can translate into meaningful improvements in AUD-related behaviors. It is a pivotal step, but it’s worth noting that it was a Phase II trial, relatively short in duration, and modest in sample size. Ongoing and future trials will need to replicate and extend these results, determining the optimal dosing, treatment duration, and whether certain subpopulations (e.g., people with comorbid obesity) benefit the most. 

Beyond Alcohol: Other Substances

AUD is the furthest along in clinical investigation with GLP-1 RAs, but researchers are probing their potential in other addictions as well. If GLP-1 modulation broadly dampens reward circuits, it might curb the use of various addictive substances. GLP-1 RAs have been shown to reduce nicotine self-administration in rats3 and attenuated cocaine-seeking behaviors in mice.4 Promising results were seen with opioid use disorder, where semaglutide was associated with significantly reduced risk of opioid overdose in a one-year follow-up period for patients with comorbid type 2 diabetes and opioid use disorder.9 The Swedish registry study mentioned earlier found that patients on semaglutide had 32% fewer hospitalizations for any substance use disorder (including drug-related incidents) compared to when they were off the medication.6 A secondary analysis of a smoking cessation trial reported that participants with comorbid type 2 diabetes receiving GLP-1 RAs were at significantly lower risk for tobacco use disorder compared with other antidiabetic medications.10 While it’s too soon to tell if GLP-1 RAs will be effective across the board, their ability to target fundamental reward and satiety pathways could make them valuable adjuncts for multiple forms of addiction if proven safe and effective. 

Side Effects and Psychiatric Considerations

Given that AUD and other addictions often coexist with mood and anxiety disorders, the psychiatric side effects of any new treatment must be carefully considered. Recently, there has been public concern about whether GLP-1 RAs might induce depression or suicidal thoughts. This concern was amplified by some post-marketing reports of increased depression or self-harm in patients using high-dose semaglutide for obesity. European regulators have launched probes to decide if black box warnings are needed for increased suicide risk. However, the current evidence does not indicate a clear increase in suicidality with GLP-1 RAs. A large meta-analysis of 27 RCTs with over 59,000 patients found no significant difference in rates of suicidal ideation or attempts between GLP-1 RAs recipients and placebo.11 In fact, in the Swedish AUD study, GLP-1 RAs treatment was not associated with any rise in suicide attempts, whereas some conventional AUD medications were linked to higher risks, suggesting a reassuring safety signal. That being said, it is important to contextualize these findings. Many patients receiving GLP-1 RAs, especially for obesity, may have pre-existing depression or be undergoing major lifestyle changes, which can affect mood. Clinicians initiating GLP-1 RAs therapy in patients with AUD should still monitor for changes in mood or emergence of depressive symptoms, as one would with any chronic illness treatment. However, the current data suggest that GLP-1 RAs do not appear to confer a significant psychiatric risk in aggregate.12 

Conclusion

The possible repurposing of GLP-1 RAs for AUD would equip clinicians with an additional tool in their arsenal. Existing AUD medications, like naltrexone, acamprosate, and disulfiram, are effective for some but far from a perfect solution, as many patients either do not respond or cannot tolerate side effects. The prospect of an existing gut hormone analog helping patients achieve sobriety is therefore compelling. As researchers race to answer these questions, clinicians can remain cautiously optimistic. If the early data hold, we may witness a paradigm shift where a hormone of the gut becomes a guardian of the mind, helping break the vicious cycle of addiction from the inside out.

By Joshua Wang is a Class of 2027 medical student at NYU Grossman School of Medicine

Reviewed by Michael Tanner, MD, Executive Editor, Clinical Correlations

Image courtesy of ??????? ??????? ?????????????, CC BY-SA 4.0 , via Wikimedia Commons

References

  1. Pearcey B. DO GLP-1 receptor agonists reduce alcohol intake in patients with obesity? Eur Med J. May 16, 2025. https://www.emjreviews.com/en-us/amj/diabetes/news/do-glp-1-receptor-agonists-reduce-alcohol-intake-in-patients-with-obesity/. Accessed May 17, 2025.
  2. Aranäs C, Edvardsson CE, Shevchouk OT, et al. Semaglutide reduces alcohol intake and relapse-like drinking in male and female rats. EBioMedicine. 2023;93:104642. doi:10.1016/j.ebiom.2023.104642
  3. Hernandez NS, Ige KY, Mietlicki-Baase EG, et al. Glucagon-like peptide-1 receptor activation in the ventral tegmental area attenuates cocaine seeking in rats. Neuropsychopharmacology. 2018;43(10):2000-2008. doi:10.1038/s41386-018-0010-3
  4. Herman RJ, Hayes MR, Audrain-McGovern J, Ashare RL, Schmidt HD. Liraglutide attenuates nicotine self-administration as well as nicotine seeking and hyperphagia during withdrawal in male and female rats. Psychopharmacology (Berl). 2023;240(6):1373-1386. doi:10.1007/s00213-023-06376-w
  5. Farokhnia M, Tazare J, Pince CL, et al. Glucagon-like peptide-1 receptor agonists, but not dipeptidyl peptidase-4 inhibitors, reduce alcohol intake. J Clin Invest. 2025;135(9). doi:10.1172/jci188314
  6. Lähteenvuo M, Tiihonen J, Solismaa A, Tanskanen A, Mittendorfer-Rutz E, Taipale H. Repurposing semaglutide and liraglutide for Alcohol Use Disorder. JAMA Psychiatry. 2025;82(1):94. doi:10.1001/jamapsychiatry.2024.3599
  7. Klausen MK, Kuzey T, Pedersen JN, et al. Does semaglutide reduce alcohol intake in Danish patients with alcohol use disorder and comorbid obesity? Trial protocol of a randomised, double-blinded, placebo-controlled clinical trial (the SEMALCO trial). BMJ Open. 2025;15(1):e086454. doi:10.1136/bmjopen-2024-086454
  8. Hendershot CS, Bremmer MP, Paladino MB, et al. Once-weekly semaglutide in adults with alcohol use disorder. JAMA Psychiatry. 2025;82(4):395. doi:10.1001/jamapsychiatry.2024.4789
  9. Wang W, Volkow ND, Wang Q, et al. Semaglutide and opioid overdose risk in patients with type 2 diabetes and opioid use disorder: A randomized clinical trial. JAMA Network Open. 2024;7(9):e2435247. doi:10.1001/jamanetworkopen.2024.35247
  10. Wang W, Volkow ND, Berger NA, Davis PB, Kaelber DC, Xu R. Association of semaglutide with tobacco use disorder in patients with type 2 diabetes: Target trial emulation using real-world data. Ann Intern Med. 2024;177(8):1016-1027. doi:10.7326/m23-2718
  11. Heffron SP. Study: GLP-1 drugs don’t raise suicide risk. NYU Langone Health Physician Focus. March 21, 2025. https://physicianfocus.nyulangone.org/reassuring-news-on-glp-1-agonists-suicide/ Accessed May 17, 2025.
  12. Ebrahimi P, Batlle JC, Ayati A, et al. Suicide and self-harm events with GLP-1 receptor agonists in adults with diabetes or obesity. JAMA Psychiatry. 2025:e250091. Published online March 19, 2025. doi:10.1001/jamapsychiatry.2025.0091

 

 

 

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