Estimating the population-level kidney benefits of improved uptake of SGLT2 inhibitors in patients with chronic kidney disease in Australian primary care

Background Although sodium glucose co-transporter 2 (SGLT2) inhibitors reduce the risk of kidney failure and death in patients with chronic kidney disease (CKD), they are underused in routine clinical practice. We evaluated the number of patients with CKD in Australia that would be eligible for treatment with an SGLT2 inhibitor and estimated the number of cardiorenal and kidney failure events that could be averted with improved uptake of SGLT2 inhibitors. Methods Using nationally-representative Australian primary care data (MedicineInsight), we identified patients that would have met inclusion criteria of the CREDENCE, DAPA-CKD, and EMPA-KIDNEY trials between 1 January 2020 and 31 December 2021. We applied these data to age and sex-stratified estimates of CKD prevalence from the broader Australian population (using national census data) to generate population-level estimates for: (1) the number of CKD patients eligible for treatment with SGLT2 inhibitors and (2) the annual number of potentially preventable cardiorenal (CKD progression, kidney failure, or death due to cardiovascular disease or kidney failure), and kidney failure events with SGLT2 inhibitors based on trial event rates. Results In MedicineInsight, 44.2% of adults with CKD would have met CKD eligibility criteria for an SGLT2 inhibitor; baseline use was 4.1%. Applying these data to the broader Australian population, we estimated 230,246 patients with CKD in Australia would have been eligible for treatment with any SGLT2 inhibitor. Optimal implementation of SGLT2 inhibitors (75% uptake in eligible patients) could reduce cardiorenal and kidney failure events annually in Australia by 3,644 (95% CI 3,526-3,764) and 1,312 (95% CI 1,242-1,385), respectively. Conclusions Improved uptake of SGLT2 inhibitors for patients with CKD in Australian primary care has the potential to prevent large numbers of patients experiencing CKD progression or dying due to cardiovascular or kidney disease. Identifying strategies to increase the uptake of SGLT2 inhibitors is critical to realising the population-level benefits of this drug class. ### Competing Interest Statement This study was supported by an unrestricted research grant from Boehringer Ingelheim. An independent study steering committee was responsible for all aspects of study conduct including study design, analysis, interpretation of study findings, reporting and the decision to submit the manuscript for publication. BLN has received fees for travel support, advisory boards, scientific presentations and steering committee roles from AstraZeneca, Bayer, Boehringer and Ingelheim, Cambridge Healthcare Research, Janssen, and Medscape with all honoraria paid to The George Institute for Global Health. He serves as Secretariat of the SGLT2 Meta-Analysis Cardio-Renal Trialists Consortium and is a member of the Caring for Australians and New Zealanders with Kidney Impairment (CARI) living guidelines on SGLT2 inhibitors. MJ is responsible for research projects that have received unrestricted research funding from Boehringer Ingelheim. SK has received consultancy fees from Chinook and Dimerix Pharmaceuticals. This study was supported by an unrestricted research grant from Boehringer Ingelheim. SVB has served on advisory board of Bayer, AstraZeneca, GSK and Vifor Pharma; received speakers fees from Bayer, AstraZeneca, Pfizer and Vifor Pharma, and non-financial research support from Bayer with all fees paid to his institution. VP has received fees for advisory boards, steering committee roles, or scientific presentations from AbbVie, Astellas, AstraZeneca, Bayer, Baxter, BMS, Boehringer Ingelheim, Dimerix, Durect, Eli Lilly, Gilead, GSK, Janssen, Merck, Mitsubishi Tanabe, Mundipharma, Novartis, Novo Nordisk, Pfizer, Pharmalink, Relypsa, Retrophin, Sanofi, Servier, Tricida, and Vitae. MW has received consultancy fees from Amgen and Freeline. ### Funding Statement This study was supported by an unrestricted research grant from Boehringer Ingelheim. An independent study steering committee was responsible for all aspects of study conduct including study design, analysis, interpretation of study findings, reporting and the decision to submit the manuscript for publication. ### 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 MedicineInsight Data Governance Committee (2020-004) and Research Ethics Review Committee of the Sydney Local Health District, NSW, Australia (X21-0428, 2020/ETH00963). 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 current study is based on data from MedicineInsight, a national general practice data source developed by NPS MedicineWise and managed by the Australian Commission on Safety and Quality in Health Care. The 2021 Australian population census data is publicly available via the Australian Bureau of Statistics website (www.abs.gov.au). All relevant data are within the manuscript and its supplementary appendix.