Among 6.4 million people with type 2 diabetes, GLP-1 receptor agonist use was associated with 37% lower suicide attempt risk overall, but this protective effect was completely absent in patients with co-occurring cannabis use disorder, who had 5.5 times higher suicide risk regardless of GLP-1 use.
Clinicians managing diabetes patients, especially those with co-occurring substance use or mental health concerns.
Cannabis use disorder associated with 5.5x higher suicide attempt risk that GLP-1 drugs did not reduce
What the researchers found
GLP-1 RA use was associated with lower suicide attempt risk (aHR 0.63). Cannabis use disorder was associated with dramatically higher risk (aHR 5.50). Among patients with both CUD and GLP-1 RA use, suicide risk remained elevated (aHR 5.75) with no significant benefit from GLP-1 RAs (aHR 1.00 comparing GLP-1 users vs non-users among CUD patients).
Why it matters
GLP-1 receptor agonists (like semaglutide/Ozempic) have generated interest for potential mental health benefits beyond metabolic effects. This study suggests their apparent protective effect against suicide does not extend to patients with cannabis use disorder, a vulnerable population with dramatically elevated baseline risk.
The numbers in context
6,424,228 individuals with T2DM. GLP-1 RA users vs unexposed: aHR 0.63 (95% CI 0.47-0.85). CUD vs no CUD: aHR 5.50 (95% CI 4.39-6.89). CUD + GLP-1 RA: aHR 5.75 (95% CI 3.42-9.69). GLP-1 RA effect among CUD patients: aHR 1.00 (95% CI 0.37-2.69).
How the study worked
Retrospective study using the TriNetX Research Network covering adults aged 30-85 with type 2 diabetes from over 20 countries (2003-2023). 6,424,228 individuals were categorized by GLP-1 RA exposure and cannabis use disorder status. Cox models estimated hazard ratios adjusted for age, sex, depression, BMI, and HbA1c. Those with prior suicidal ideation were excluded.
What this study cannot tell us
Retrospective design with potential confounding despite adjustment. Cannabis use disorder codes may capture only the most severe cases. GLP-1 RA users may differ systematically from non-users. The CUD + GLP-1 subgroup may be too small for adequate power. Claims data cannot capture suicidal behavior that does not result in healthcare contact.
How to read the evidence
Very large international retrospective cohort with adjusted analyses, but limited by observational design and potential selection bias.
When this study was published
Published in 2025, using data from 2003-2023.
The bigger picture
The 5.5-fold suicide risk associated with cannabis use disorder in diabetes is striking and largely independent of GLP-1 treatment. This suggests that CUD represents a powerful risk factor that may overwhelm whatever neuroprotective mechanisms GLP-1 drugs provide, highlighting the need for integrated psychiatric and substance use screening in diabetes care.
Questions still open
- Why does cannabis use disorder nullify the apparent GLP-1 protective effect? Is the elevated suicide risk driven by cannabis itself, or by the broader psychosocial factors associated with CUD diagnoses? Would addressing CUD in these patients restore the GLP-1 benefit?
Common questions
Do GLP-1 drugs prevent suicide?
Why is cannabis use disorder linked to such high suicide risk?
Read the original research
Glucagon-like peptide-1 receptor agonists and suicide risk in individuals with diabetes and Cannabis use disorder.
Preventive medicine reports, 58, 103244
Citation
Dhruva, Yesh; Messias, Erick; Lin, Ping-I. (2025). Glucagon-like peptide-1 receptor agonists and suicide risk in individuals with diabetes and Cannabis use disorder.. Preventive medicine reports, 58, 103244. https://doi.org/10.1016/j.pmedr.2025.103244
Explore the wider topic
- Physical vs Psychological Cannabis Dependence: What Science Actually Shows
- The Gap Between Cannabis Perception and Science: Why What We Believe Outpaces What We Know
- Cannabis Use Disorder: Am I Addicted? Self-Assessment Guide
- Cross-Addiction After Quitting Weed: When One Habit Replaces Another
- Is Weed Addictive? What the Research Actually Shows
- Is Cannabis Addictive? What the DSM-5 and Brain Science Say
- Quitting Weed and Alcohol Together: What to Know About Dual Cessation
- Is Rehab Necessary for Weed? An Honest Assessment
- Signs You May Have Cannabis Use Disorder: An Honest Self-Assessment
- Weed Vape Pen Addiction: Why Vaping Makes It Harder to Quit