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

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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement N/A ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (HKU/HA HKWC IRB) (UW-20-250) and complied with the Declaration of Helsinki. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data that support the findings of this study were provided by the Hong Kong Hospital Authority, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of Hong Kong Hospital Authority.