Cancer outcomes and biological mechanisms among patients with type 2 diabetes mellitus using glucagon-like peptide-1 receptor agonists: a systematic review and meta-analysis.
Level 3 - non-randomized controlled study
Systematic review relying predominantly on observational cohort studies.
PubMed 42523690 · doi:10.3389/fonc.2026.1859759
What was done
A systematic review and meta-analysis was conducted according to PRISMA 2020 guidelines by searching PubMed, Scopus, and Web of Science through June 2026. Studies evaluating cancer outcomes in adults with type 2 diabetes mellitus exposed to glucagon-like peptide-1 receptor agonists (GLP-1RAs) were included. Hazard ratios (HRs) were pooled using the Generic Inverse Variance method under a random-effects model.
What was found
GLP-1RA use was associated with a statistically significant reduction in overall cancer risk (HR = 0.86, 95% CI: 0.74–0.99; p = 0.04). Subgroup analyses by site showed significant reductions in pancreatic, colorectal, endometrial, ovarian, hepatocellular, esophageal, and gastric cancers. No significant associations were observed for thyroid, breast, kidney, or prostate cancers. Direct mechanistic evidence regarding cellular pathways was sparse and mostly indirect.
Why it matters
This review provides reassuring evidence that GLP-1RAs do not increase malignancy risk in patients with type 2 diabetes and may confer protective effects against several obesity- and diabetes-related cancers.
Limits
The abstract does not state the number of included studies, total participant count, or effect sizes for specific cancer subtypes. Findings are limited by substantial heterogeneity, reliance on observational data with potential confounding, and limited mechanistic validation.
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