Sodium-glucose cotransporter-2 inhibitors and the risk of lung cancer among patients with type 2 diabetes: a retrospective cohort study

Objective To determine whether the use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors, compared to dipeptidyl peptidase 4 (DPP-4) inhibitors, is associated with a decreased risk of incident lung cancers among patients with type 2 diabetes. Methods We assembled a new-user, active comparator cohort of SGLT-2 inhibitor and DPP-4 inhibitor users using the United Kingdom Clinical Practice Research Datalink. We fit Cox proportional hazards models with propensity score fine stratification weighting to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for incident lung cancers. Results Crude lung cancer incidence rates were 0.92 and 1.37 per 1,000 person-years among 47,517 SGLT-2 inhibitor and 129,807 DPP-4 inhibitor users, respectively. No reduced risk of lung cancer was observed among SGLT-2 inhibitor users after weighting (HR 1.08, 95% CI 0.78–1.48). Conclusions: In this large cohort study, the use of SGLT-2 inhibitors was not associated with a decreased risk of lung cancer. ### Competing Interest Statement L.A. received consulting fees from Janssen and Pfizer unrelated to this project. No other potential conflicts of interest relevant to this article were reported. ### Funding Statement This research was funded by a Foundation Scheme grant from the Canadian Institutes of Health Research (FDN-143328). ### 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: The United Kingdom Clinical Practice Research Datalink Independent Scientific Advisory Committee gave ethical approval for this work (protocol 22_001710). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes No data are available. This study is based on data from the Clinical Practice Research Datalink obtained under license from the UK Medicines and Healthcare products Regulatory Agency. The data are provided by patients and collected by the UK National Health Service as part of their care and support. The interpretation and conclusions contained in this study are those of the author/s alone. Because electronic health records are classified as "sensitive data" by the UK Data Protection Act, information governance restrictions (to protect patient confidentiality) prevent data sharing via public deposition. Data are available with approval through the individual constituent entities controlling access to the data. Specifically, the primary care data can be requested via application to the Clinical Practice Research Datalink ().