Nasopharyngeal Carcinoma and Head and Neck Cancer in Patients with Type-2 Diabetes Mellitus receiving SGLT2I, DPP4I or GLP1a: A population-based cohort study

Abstract

Introduction: Nasopharyngeal carcinoma (NPC) remains endemic in Asian regions, which risk factors were distinct from other head and neck (H&N) cancers. Anti-diabetic drugs has 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. Method: This was a retrospective population-based cohort study including T2DM patients treated with either SGLT2I or DPP4I between 1st January 2015 and 31st December 2019 in Hong Kong. The primary outcome was new-onset NPC and other H&N cancer. The secondary outcome was cancer-related mortality. Propensity score matching (1:1 ratio) was performed using the nearest neighbour search. Multivariable Cox regression was applied to identify significant predictors. Results: 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 (0.18%), and 50 patients developed H&N cancer (0.08%). Compared to DPP4I, SGLT2I was associated with significantly 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 result remained significant regardless of demographics and obesity. The association remained consistent in different risk models, matching approaches, and the sensitivity analysis. Conclusion: This study provides real-world evidence that SGLT2I was associated with lower risks of NPC, but not H&N cancer compared to DPP4I after adjustments amongst T2DM patients.