Ko · Annals of internal medicine 2026 · systematic review and meta-analysis of randomized placebo-controlled trials · n=48 trials (94,245 participants)

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

Cited 23 times in the scientific literature.

Level 1 - systematic review of randomized trials

Systematic review and meta-analysis of randomized controlled trials

PubMed 41359966 · doi:10.7326/ANNALS-25-02237 · record verified 2026-08-27

What was done

Systematic review and random-effects meta-analysis of randomized placebo-controlled trials identified in PubMed, Embase, Web of Science, Scopus, and CENTRAL up to August 2025. Eligible studies evaluated GLP-1 receptor agonists or dual agonists in adults with type 2 diabetes or overweight/obesity and reported pre-specified cancer outcomes. Risk of bias was assessed using Cochrane RoB 2, and certainty of evidence was graded with the GRADE framework.

What was found

Across 48 randomized trials encompassing 94,245 participants, GLP-1 receptor agonists probably have little or no effect on: - Thyroid cancer: OR 1.37 (95% CI, 0.82 to 2.31; 1 fewer to 9 more cases per 10,000 patients treated; moderate certainty) - Pancreatic cancer: OR 0.84 (95% CI, 0.53 to 1.35; 9 fewer to 6 more per 10,000; moderate certainty) - Breast cancer: OR 0.95 (95% CI, 0.60 to 1.49; 10 fewer to 12 more per 10,000; moderate certainty) - Kidney cancer: OR 1.12 (95% CI, 0.78 to 1.60; 5 fewer to 13 more per 10,000; moderate certainty) Low-certainty evidence indicated little or no effect on colorectal, esophageal, liver, gallbladder, ovarian, or endometrial cancer, multiple myeloma, or meningioma. The effect on gastric cancer was very uncertain. Results remained consistent in sensitivity analyses of low-risk trials and specific agents (semaglutide, tirzepatide).

Why it matters

This large meta-analysis provides reassurance that GLP-1 receptor agonists and dual agonists do not measurably increase short- to medium-term risk of obesity-related cancers.

Limits

The included randomized trials were not primarily designed to evaluate cancer outcomes and had relatively short follow-up periods to fully capture long-latency malignancies.

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