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News|Articles|March 5, 2026

GLP-1s Reduced Risk of Developing Substance Use Disorders

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Key Takeaways

  • Target-trial emulation in VA EHRs constructed eight parallel new-user trials comparing GLP-1 RA initiators with SGLT-2 inhibitor initiators under two protocols: incident SUDs and SUD-related adverse outcomes.
  • In 524,817 adults with T2D, GLP-1 RA use was associated with lower incident alcohol, cocaine, cannabis, opioid, and nicotine use disorders (HRs 0.75–0.86 across subtypes).
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In a cohort of US veterans, there were reduced risks of adverse clinical outcomes in people with SUDs and of developing an SUD in those taking GLP-1s.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have primarily been used to treat diabetes and obesity after FDA approvals for those indications changed the landscape of those chronic conditions. However, there may be even more uses of GLP-1 RAs in practice that go beyond obesity and diabetes alone. A new study published in BMJ has shown that US veterans taking GLP-1 RAs for diabetes had a reduced risk of developing incident substance use disorder (SUD) compared with those not taking the treatment.1

GLP-1 RAs had shown promise in treating alcohol use disorder,2 cannabis use disorder, and tobacco use disorder in previous studies, but the effect of using them to treat SUDs overall was less studied, usually focusing on 1 or 2 specific SUDs.1 Studies have also shown that GLP-1 RAs may reduce the risk of adverse events related to SUDs, such as overdose and risk of hospital admission for alcohol use disorder. This study aimed to estimate the average treatment effect of GLP-1 RAs in this population over a 3-year follow-up period.

The study was observational in design and emulated 8 parallel new user target trials based on the electronic health records (EHRs) from the US Department of Veteran Affairs. The trials followed 2 protocols, with the first protocol evaluating incidence of SUDs and protocol 2 evaluating adverse outcomes in those with SUDs. The EHRs from the US Department of Veteran Affairs database were used for the study, which holds records from 170 medical centers and 1193 outpatient clinics. All participants had prescription coverage of GLP-1 RAs.

The first protocol enrolled participants who were 18 years or older, were active users of the Veteran Affairs health care system, and had a diagnosis of type 2 diabetes. Patients were excluded if they had contraindications within the past year or had used a GLP-1 RA or sodium-glucose cotransporter-2 (SGLT-2) inhibitor in the year before enrollment. The second protocol had the same eligibility criteria as the first protocol, along with a diagnosis of SUD in the year before the enrollment. The same exclusion criteria applied.

Outpatient pharmacy records were used to define drug use. The primary outcome was to define the relationship between the risk of incident SUDs and the use of GLP-1 RAs, measured through emergency department visits, hospital admissions, and mortality related to SUDs.

There were 524,817 participants included in protocol 1, of which 124,001 used GLP-1 RAs. The researchers found a reduced risk of incident SUDs in those using GLP-1 RAs. This included alcohol use (HR, 0.82; 95% CI, 0.78-0.85), cocaine use (HR, 0.80; 95% CI, 0.72-0.88), cannabis use (HR, 0.86; 95% CI, 0.81-0.90), opioid use (HR, 0.75; 95% CI, 0.67-0.85), and nicotine use (HR, 0.80; 95% CI, 0.74-0.87).

There were 81,617 participants in protocol 2, of which 16,768 were taking GLP-1 RAs. Reduced risks of emergency department visits (HR, 0.69; 95% CI, 0.61-0.78), hospital admissions (HR, 0.74; 95% CI, 0.65-0.85), and mortality (HR, 0.50; 95% CI, 0.32-0.79) were found in patients who started using GLP-1 RAs and had pre-existing SUDs.

There were some limitations to this study. The Veterans Affairs’ database primarily includes data for patients who are older, White, and men, which could limit generalizability. Residual confounding could also be possible despite design features meant to mitigate bias. Misclassification is possible with electronic health data. The study primarily compares the use of GLP-1 RAs vs SGLT2s and does not compare them against no treatment. Event counts were small in some of the SUD subtypes.

The researchers concluded that “use of GLP-1 [RAs] was associated with reduced risk of a broad array of incident SUDs, suggesting potential preventive effects across a range of substances.”

References

  1. Cai M, Choi T, Xie Y, Al-Aly Z. Glucagon-like peptide-1 receptor agonists and risk of substance use disorders among US veterans with type 2 diabetes: cohort study. BMJ. 2026;392:e086886. doi:10.1136/bmj-2025-086886
  2. 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. doi:10.1001/jamapsychiatry.2024.4789

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