GLP-1s blunt addiction risk across alcohol, opioids, nicotine, and cocaine

Clinical takeaway: Clinicians treating patients with diabetes or obesity, who also struggle with substance use disorders, may have additional reason to consider these medications. Alcohol use disorder is the furthest along in clinical testing, with additional randomized controlled trials anticipated.

The case for GLP-1s in addiction medicine has been building. Early trial data in alcohol use disorder and scattered signals in opioid and nicotine research have shown positive results. A new large real-world study pulls the addiction threads together, finding lower odds of four distinct substance use disorders among GLP-1 users with diabetes or obesity.

GLP-1 users had lower odds of new diagnoses across all four substance categories: 74% lower odds of alcohol use disorder, 69% lower odds of opioid use disorder, 68% lower odds of nicotine use disorder, and 75% lower odds of cocaine use disorder. In a separate analysis pooling all substance use disorder diagnoses, GLP-1 use was associated with 75% lower odds overall.

Researchers conducted a nested case-control study using data from more than 142,000 adults with type 2 diabetes or obesity enrolled in the NIH All of Us Research Program. GLP-1 users were matched to non-users on age, sex, race, ethnicity, and diabetes or obesity status. GLP-1 exposure was defined as a prescription fill at least 90 days before a substance use disorder diagnosis.

The consistency of associations across four chemically distinct substances is the study's most compelling feature, pointing to a shared mechanism rather than substance-specific effects. Researchers believe GLP-1 receptors expressed in the brain's reward regions, including the ventral tegmental area and nucleus accumbens, may dampen dopamine signaling in ways that reduce craving and compulsive drug-seeking behavior across substance types.

"Our next goal is to conduct prospective research that follows individuals initiating GLP-1 therapy over time. We aim to evaluate whether changes in the substance use behaviors occur after treatment begins and whether these changes related to improvements in mental health and quality of life," said lead author Tadesse Abegaz, Ph.D., of the University of Texas at El Paso School of Pharmacy. The researchers explicitly caution against off-label prescribing for addiction ahead of randomized clinical trials in each specific indication.

Source: Abegaz et al. Frontiers in Psychiatry. March 10, 2026. Association between GLP-1 receptor agonist use and substance use disorders among individuals with type 2 diabetes or obesity: a nested case-control study in the All of Us research program