BACKGROUND AND PURPOSE:

• Whether GLP-1RAs, such as semaglutide or tirzepatide, are associated with cancer risk is unclear
• Ko et al. (Annals of Internal Medicine, 2025) investigated the risk for obesity-related cancer associated with GLP-1RAs

METHODS:

• Systematic review and meta-analysis
• Inclusion criteria
  • Randomized placebo-controlled trials
  • Studies that reported on cancer outcomes
    • Thyroid | Pancreatic | Colorectal | Gastric | Esophageal | Liver | Gallbladder | Breast | Ovarian | Endometrial | Kidney | Multiple myeloma | Meningioma
• Study design
  • Risk of bias was assessed
  • Certainty of evidence was assessed with GRADE criteria
  • Random-effects meta-analysis was used to generate pooled odds ratios
• Primary outcome
  • Cancer risk

RESULTS:

• 48 trials | 94,245 participants
• GLP-1RAs probably have little or no effect on risk of
  • Thyroid cancer
    • Odds ratio (OR) 1.37 (95% CI, 0.82 to 2.31)
    • –1 to 9 cases per 10,000 patients treated | Moderate certainty
  • Pancreatic cancer
    • OR 0.84 (95% CI, 0.53 to 1.35)
    • –9 to 6 per 10,000 patients treated | Moderate certainty
  • Breast cancer
    • OR 0.95 (95% CI, 0.60 to 1.49)
    • –10 to 12 per 10,000 patients treated | Moderate certainty
  • Kidney cancer
    • OR 1.12 (95% CI, 0.78 to 1.60)
    • –5 to 13 per 10,000 patients treated | Moderate certainty
• GLP-1RAs may have little or no effect on
  • Colorectal | Esophageal | Liver | Gallbladder | Ovarian | Endometrial cancer
  • Multiple myeloma | Meningioma
  • All low certainty
• The effect of GLP1-RAs on gastric cancer is very uncertain
• These results remained the same after additional analyses
  • Trials with low risk of bias
  • Studies on semaglutide or tirzepatide
• Results were also consistent across subgroups stratified by
  • Follow-up duration | Population | GLP-1RA class | Weight loss profile | Dose | Duration of action

CONCLUSION:

• GLP1-RAs may have little to no impact on the risk of cancers associated with obesity
• While the strength of this study is the use of RCTs, follow-up time was limited
• The authors state

Taken together, these findings offer important insights into the safety of GLP-1RAs but highlight the need for longer-term studies with cancer-specific end points to clarify potential risks or protective effects

Learn More – Primary Sources:

Risk for Cancer With Glucagon-Like Peptide-1 Receptor Agonists and Dual Agonists: A Systematic Review and Meta-analysis