Nasopharyngeal carcinoma (NPC) remains a major endemic disease in parts of Asia especially Southern China and Southest Asia, the risk factors of which are distinct from other head and neck cancers. Antidiabetic drugs have been proposed to reduce the risk of NPC. The associations between sodium–glucose cotransporter 2 inhibitors (SGLT2I) versus dipeptidyl peptidase-4 inhibitors (DPP4I) and the risks of NPC and head and neck cancer among patients with type 2 diabetes mellitus (T2DM) remain unknown. This was a population-based cohort study including patients with T2DM treated with either an SGLT2I or a DPP4I between January 1, 2015, and December 31, 2019, in Hong Kong. Propensity score matching (1:1 ratio) was performed using the nearest neighbor search. Multivariable Cox regression was applied to identify significant predictors. The primary outcome was new-onset NPC and other head and neck cancers. We found that patients with T2DM were treated with either an SGLT2I or a DPP4I between January 1, 2015, and December 31, 2019, in Hong Kong. This cohort included 75,884 patients with T2DM, among whom 28,778 patients were on an SGLT2I and 47,106 patients were on a DPP4I. After matching (57,556 patients), 106 patients developed NPC and 50 patients developed head and neck cancer. Compared with DPP4Is, SGLT2Is were associated with lower risks of NPC (HR, 0.41; 95% confidence interval, 0.21–0.81) but not of head and neck cancer (HR, 1.00; 95% confidence interval, 0.26–3.92) after adjustments. The association remained consistent in different risk models, matching approaches, and sensitivity analysis. In conclusion, this study provided real-world evidence that SGLT2Is were associated with lower risks of NPC but not of head and neck cancer when compared with DPP4Is among patients with T2DM, whereas their biological effects need future confirmation.

Prevention Relevance:

This study provided real-world evidence that SGLT2Is were associated with lower risks of NPC but not of head and neck cancer when compared with DPP4Is among patients with T2DM. SGLT2Is should be considered before DPP4Is about the risks of NPC in regions with high prevalence of NPC.

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©2025 The Authors; Published by the American Association for Cancer Research
2025
American Association for Cancer Research
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First page of Nasopharyngeal Carcinoma and Head and Neck Cancer in Type 2 Diabetes after SGLT2I, DPP4I, and GLP1a Use<alt-title alt-title-type="short">SGLT2I, DPP4I, and GLP1a for Head and Neck Cancers in T2DM</alt-title>

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