Nasopharyngeal Carcinoma and Head and Neck Cancer in Type 2 Diabetes after SGLT2I, DPP4I, GLP1a Use.

Nasopharyngeal carcinoma (NPC) remains endemic in Asia, which risk factors were distinct from other head and neck (H&N) cancers. Anti-diabetic 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 H&N cancer amongst type-2 diabetes mellitus (T2DM) patients remains unknown. This was a population-based cohort study including T2DM patients treated with either SGLT2I or DPP4I between 1st January 2015 and 31st December 2019 in Hong Kong. Propensity score matching (1:1 ratio) was performed using the nearest neighbour search. Multivariable Cox regression was applied to identify significant predictors. The primary outcome was new-onset NPC and other H&N cancer. We found that T2DM patients treated with either SGLT2I or DPP4I between 1st January 2015 and 31st December 2019 in Hong Kong. This cohort included 75,884 patients with T2DM, amongst whom 28,778 patients were on SGLT2I and 47,106 patients were on DPP4I. After matching (57556 patients), 106 patients developed NPC, and 50 patients developed H&N cancer. Compared to DPP4I, SGLT2I was associated with lower risks of NPC (Hazard ratio [HR]: 0.41; 95% Confidence interval [CI]: 0.21-0.81) but not H&N cancer (HR: 1.00; 95% CI: 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 SGLT2I was associated with lower risks of NPC, but not H&N cancer, compared to DPP4I amongst T2DM patients, while their biological effects needs future confirmation.