GLP-1 Receptor Agonists Linked to Reduced Substance Use Disorder Risk

HealthDay News — Latest research indicates that the use of glucagon-like peptide-1 (GLP-1) receptor agonists, medications primarily used to treat type 2 diabetes, is associated with a reduced risk of developing substance use disorders (SUDs). The study, published online March 4 in The BMJ, adds to a growing body of evidence suggesting potential benefits beyond glycemic control.

Study Details and Findings

Researchers, led by Miao Cai, Ph.D., from the VA Saint Louis Health Care System, investigated whether initiating GLP-1 receptor agonists correlated with a lower incidence of SUDs in individuals without a prior history of substance use, and whether it reduced the risk of adverse clinical outcomes in those with pre-existing SUDs. The study utilized data from the US Department of Veterans Affairs, analyzing records of 606,434 veterans with type 2 diabetes.

The research involved the emulation of eight parallel trials, comparing outcomes between individuals starting GLP-1 receptor agonists and those initiating sodium-glucose cotransporter-2 (SGLT-2) inhibitors – another class of diabetes medications.

The primary trial included 524,817 patients (124,001 GLP-1 initiators and 400,816 SGLT-2 initiators). A secondary protocol examined 81,617 patients (16,768 GLP-1 initiators and 64,849 SGLT-2 initiators) with pre-existing SUDs.

Key findings revealed that GLP-1 receptor agonist initiation was associated with a reduced risk of disorders related to:

• Alcohol use (hazard ratio 0.82)
• Cannabis use (hazard ratio 0.86)
• Cocaine use (hazard ratio 0.80)
• Nicotine use (hazard ratio 0.80)
• Opioid use (hazard ratio 0.75)
• Other SUDs (hazard ratio 0.87)

The composite outcome of all incident SUDs likewise showed a reduced risk with GLP-1 receptor agonists (hazard ratio 0.86). Among individuals with pre-existing SUDs, GLP-1 receptor agonists were linked to a decreased risk of SUD-related emergency department visits, hospital admissions, mortality, drug overdose, and suicidal ideation or attempt.

Implications and Future Research

The authors suggest that the mechanism behind this association may involve GLP-1 receptor agonist-related agonism preventing addiction phenotypes across various drug classes. While the study demonstrates a strong correlation, further research is needed to establish a causal link and elucidate the underlying biological mechanisms.

“Our results show that GLP1 receptor agonist-related agonism may prevent addiction phenotypes across all major drug classes,” the authors wrote in the study.

one author disclosed ties to Pfizer.

Sources:

• Cai M, et al. Glucagon-like peptide-1 receptor agonists and risk of substance use disorders among US veterans with type 2 diabetes: cohort study. The BMJ. Published online March 4, 2026.
• GLP-1 Receptor Agonist Use Linked to Reduced Risks for Substance Use Disorder.