Cannabis use linked to higher risks in diabetes treatment study

Cannabis use is rising among adults with type 2 diabetes mellitus (T2DM). Whether cannabis use modifies the cardio-renal benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) is unknown. Retrospective propensity score-matched cohort study in the TriNetX Research Network (January 2017-December 2025). Adults with T2DM initiating GLP-1 RA therapy were classified as people who use cannabis (≥2 ICD-10-CM F12.x codes within 2 years before index) or as people who did not (the comparison cohort). 1:1 matching was performed on more than 40 baseline covariates. The primary outcome was all-cause mortality; secondary outcomes were 4-point major adverse cardiovascular events (MACE) and major adverse kidney events (MAKE). Cox models estimated hazard ratios (HRs); E-values assessed robustness to unmeasured confounding. Among 614,333 eligible patients, 4117 people who use cannabis were matched to 4117 comparison patients (median follow-up 2.6 years). Cannabis use was associated with increased all-cause mortality (HR 1.64, 95% CI 1.38-1.96), MACE (HR 1.42, 1.26-1.59), and MAKE (HR 1.55, 1.34-1.79). A dose-response was observed: cannabis use disorder (HR 2.20) conferred greater mortality risk than non-disordered use (HR 1.73). Associations persisted across sensitivity and subgroup analyses; E-values were 2.21-2.63. In an exploratory analysis, concomitant sodium-glucose cotransporter-2 (SGLT-2) inhibitor therapy was associated with lower mortality (HR 0.62, 0.45-0.85) and MAKE (HR 0.70, 0.54-0.92) in this group. Cannabis use was associated with substantially higher mortality, cardiovascular, and renal risk among patients with T2DM initiating GLP-1 RAs, with a dose-response pattern. Clinicians should inquire about cannabis use when prescribing GLP-1 RAs.