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GLP ‐1 Receptor Agonists and Risk of Skin Cancer in Adults With Type 2 Diabetes: A Target Trial Emulation

Year: 2026

Type: article

Abstract: AIMS: Existing evidence regarding the association between glucagon-like peptide-1 receptor agonists (GLP-1RAs) and risk of melanoma and non-melanoma skin cancer (NMSC) is inconclusive. This study aimed to assess the association between GLP-1RA initiation and risks of melanoma and NMSC versus sodium-glucose cotransporter 2 inhibitors (SGLT2is) and dipeptidyl peptidase 4 inhibitors (DPP4is) in adults with type 2 diabetes (T2D). MATERIALS AND METHODS: Target trial emulation using TriNetX electronic health records (2014-2025). Adults with T2D initiating GLP-1RAs, SGLT2is or DPP4is were included. Outcomes were incident melanoma and NMSC over 3 years. Propensity score matching and Cox models estimated hazard ratios (HRs). Sensitivity analyses included negative control outcome (NCO) calibration, a lag-period analysis and restriction to patients with obesity. RESULTS: After matching, the GLP-1RA versus SGLT2i cohort included 235 797 pairs; the GLP-1RA versus DPP4i cohort included 153 873 pairs. Mean follow-up ranged from 1.8 to 2.2 years. GLP-1RA use was not associated with melanoma compared with either SGLT2i (HR, 1.04; 95% CI, 0.93-1.17) or DPP4i (HR, 1.09; 95% CI, 0.95-1.25). A borderline increase in NMSC risk was observed in the comparison with SGLT2is (HR, 1.06; 95% CI, 1.00-1.11); no such association was identified in the comparison with DPP4is (HR, 1.03; 95% CI, 0.97-1.09). Findings were generally consistent across sensitivity analyses; however, the association with NMSC was attenuated after NCO calibration. CONCLUSIONS: GLP-1RA therapy was not associated with an increased risk of melanoma. A borderline increase in NMSC risk was observed compared with SGLT2is but was not evident after NCO calibration.

Source: Diabetes Obesity and Metabolism

DOI: 10.1111/dom.71142