Glucagon-like Peptide-1 Receptor Agonists and Risk of Thyroid Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Abstract Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are effective drugs for the treatment of type 2 diabetes mellitus and the management of obesity. Although these medications are generally safe, concerns have emerged regarding the possible link between GLP-1 RA use and thyroid cancer, particularly medullary thyroid carcinoma. This systematic review and meta-analysis aimed to investigate the association between GLP-1 RA use and the risk of all types of thyroid cancer. Materials and Methods: A systematic search was performed using Embase, PubMed/Medline, the US Clinical Trials Registry, and Google Scholar up to July 2024 for randomized controlled trials (RCTs) on GLP-1 RAs in diabetic or overweight/obese adults with at least 24 weeks of treatment and reported thyroid cancer incidence. A random-effects meta-analysis model was used to calculate the odds ratio (OR) and the 95% confidence interval (CI) of the risk of thyroid cancer in the GLP-1 RA group compared to control groups. Assessments of subgroup analyses and publication bias were also performed. Results: Of the 44 RCTs in the meta-analysis, which involved 84,472 study participants, there was no significant association between the use of GLP-1 RAs and thyroid cancer when compared to control groups (OR = 1.11; 95% CI = 0.74–1.69). In the subgroup analysis based on the comparators, population, and type of GLP-1 RAs, no significant association was found to be associated with the risk of thyroid cancer. Conclusion: The analysis showed no increased risk of thyroid cancer with GLP-1 RAs use. However, large-scale, long-term studies are necessary given the very low incidence of thyroid cancer and variations in the duration of treatment.