Cancer Incidence Among Users of Glucagon-Like Peptide-1 Receptor Agonists.

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are novel antidiabetic agents that may influence cancer risk. While some studies suggest protective effects, others raise concerns about potential oncogenic associations. To investigate the risk of common cancers with GLP-1RA initiation. Retrospective cohort study. Patients diagnosed with type 2 diabetes between 2013-2021 were identified using IBM-MarketScan database and were categorized into exposure (i.e., GLP-1RA) and comparison (i.e., insulin) groups. Overlap Propensity Score Weighting (OPSW), followed by Cox proportional hazards models, was used to assess cancer risk. Among 106,088 patients, most were male (n = 44,059, 51.3%), and the mean age was 51 (SD: ± 9.8) years; 50.8% (n = 53,924) of patients had GLP-1RA initiation. Overall, 1.9% (n = 1,594) of the individuals developed cancer (thyroid: n = 110, 0.1%; lung: n = 127, 0.1%; breast: n = 369, 0.4%; esophagus: n = 20, 0.02%; gastric: n = 34, 0.03%; liver: n = 116, 0.1%; biliary: n = 20, 0.02%; pancreatic: n = 87, 0.1%; small intestine: n = 23, 0.02%; renal: n = 128, 0.1%; bladder: n = 66, 0.1%; colorectal: n = 175, 0.2%; prostate: n = 322, 0.4%; ovarian: n = 51, 0.1%; endometrial: n = 130, 0.2%; neuroendocrine: n = 60, 0.1%). Compared to insulin, GLP-1RA medications were associated with a significantly lower risk of liver cancer (HR: 0.47, 95% CI: 0.27-0.82) and pancreatic cancer (HR: 0.23, 95% CI: 0.11-0.51). Risk of all other cancers remained comparable between the two groups (all p > 0.05). GLP-1RA use was associated with a lower incidence of liver and pancreatic cancer, with no increased risk observed for other major cancers. As these medications become more widely used, further research is warranted to better define their long-term cancer-related safety profile.