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Glucagon-like peptide 1 receptor agonists (GLP1Ra) are commonly used in type 2 diabetes mellitus (T2DM). However, differential risk of various cancers among GLP1Ra recipients is unknown. We inquired an aggregated electronic health record database, Explorys, and compared the adjusted odds ratio (aOR) of cancers between GLP1Ra and metformin users. Findings were validated in the FDA Adverse Event Reporting System (FDA FAERS). From 1/2005 to 6/2019, we identified 619 340 and 64 230 patients in the metformin and GLP1Ra group, respectively. Within 5 years of starting antidiabetic medications, GLP1Ra was associated with significantly lower incident risk of prostate (aOR 0.81,  p  = .03), lung (aOR 0.81,  p  = .05), and colon cancer (aOR 0.85,  p  = .03), while the risk of thyroid cancer was significantly higher (aOR 1.65,  p  &lt; .01). Similar findings were seen in the FDA FAERS database, where GLP1Ra was associated with lower risk of prostate (aOR 0.72,  p  = .08), lung (aOR 0.52,  p  &lt; .01), colon cancer (aOR 0.82,  p  = .31), and higher risk of thyroid cancer (aOR 4.33,  p  &lt; .01). In addition, with longer duration of GLP1Ra use, the risk of prostate, lung, and colon cancer further decreased, suggesting an exposure duration–response relationship. GLP1Ra is associated with lower risks of prostate, lung, and colon cancer, but higher risk of thyroid cancer.

Differential Risk of Cancer Associated with Glucagon-like Peptide-1 Receptor Agonists: Analysis of Real-world Databases