Incretin-Based Therapy and Thyroid Cancer Risk: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background The association between incretin-based therapies, including glucagon-like peptide-1 receptor agonists and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists, and thyroid cancer risk remains controversial. Conflicting observational findings highlight the need for evidence derived exclusively from randomized controlled trials (RCTs). Objectives To evaluate the association between incretin-based therapies and thyroid cancer risk using RCT data. Methods We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, EMBASE, and ClinicalTrials.gov were searched through January 4, 2026, for RCTs of approved incretin-based therapies with ≥26 weeks of follow-up that reported thyroid cancer events. Data extraction was performed independently by 2 reviewers. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Pooled odds ratios and 95% CIs were calculated using a random-effects model. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. Results Fifteen RCTs enrolling 84 237 participants were included. Across all trials, 28 thyroid cancer events occurred in the incretin-based therapy groups and 15 in the control groups. Meta-analysis showed no statistically significant association between incretin-based therapy use and thyroid cancer risk (odds ratio 1.52, 95% CI 0.86–2.68; I2 = 0.0%). Findings were consistent across prespecified subgroup and sensitivity analyses. Certainty of evidence was rated very low due to serious imprecision related to rare events. Conclusions RCT evidence does not demonstrate a statistically significant increase in thyroid cancer risk with incretin-based therapies. However, limited follow-up and imprecision prevent exclusion of a clinically relevant increase, supporting the need for long-term surveillance.