A total of 54,308 patients with and initiated sodium-glucose cotransporter-2 inhibitors (SGLT2i) across various health databases.
Crude incidence rates of kidney and heart failure were generally higher in the glucagon-like peptide-1 receptor agonist (GLP-1 RA) cohorts compared to SGLT2i cohorts.
The study included data from multiple sources, including Danish National Health Registers and US Optum Electronic Health Records.
Baseline clinical profile differences were identified between new users of SGLT2i and GLP-1 RA.
The incidence of kidney failure and cardiovascular outcomes in patients receiving these antidiabetic medications is important for future comparisons of CKD treatments.
Simplified
INTRODUCTION: People with (CKD) and (T2D) have an increased risk of kidney failure and cardiovascular disease. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) have shown cardiorenal protective effects. The objective of this multinational, multidatabase study was to describe the incidence of kidney and cardiovascular outcomes in separate, non-mutually exclusive cohorts of patients with CKD and T2D who initiated either an SGLT2i or a GLP-1 RA.
METHODS: Data describing adults (≥ 18 years) with T2D and CKD who were new users of either SGLT2i or GLP-1 RA from 2012 to 2019 were assessed from population-based Danish National Health Registers (DNHR) and Valencia Health System Integrated Database (VID), hospital-based Japan Chronic Kidney Disease Database Extension (J-CKD-DB-Ex), and US Optumde-identified Electronic Health Record dataset (Optum EHR). Crude incidence rates (IRs) and 95% confidence intervals (CIs) for primary outcomes (kidney failure, acute coronary syndrome, stroke, new-onset congestive heart failure, new-onset atrial fibrillation) and cumulative incidence by follow-up time for primary and secondary outcomes (laboratory measurements of kidney function) were estimated. ® ®
RESULTS: SGLT2i cohorts comprised 12,501 patients in DNHR, 22,404 in VID, 811 in J-CKD-DB-Ex, and 54,308 in Optum EHR. GLP-1 RA cohorts comprised 10,696 in DNHR, 8317 in VID, 219 in J-CKD-DB-Ex, and 78,934 in Optum EHR. Baseline clinical profile differences were observed for GLP-1 RA and SGLT2i new users, and crude IRs of kidney and heart failure tended to be higher in the GLP-1 RA cohorts than in the SGLT2i cohorts across data sources. ® ®
CONCLUSION: Understanding the incidence of kidney failure and cardiovascular outcomes in people receiving antidiabetic medications with cardiorenal protective effects is important for future studies aiming to compare the incidence of kidney and cardiovascular outcomes related to new and existing CKD treatments.
Key numbers
1.20 events per 1000 PY
Kidney Failure ()
during follow-up in the cohort.
15.19/1000 PY
Atrial Fibrillation ()
Most common cardiovascular outcome in the cohort.
0.27–8.88 events per 1000 PY
Kidney Failure ()
Incidence rates of kidney failure in the cohort across data sources.
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Declarations. Conflict of Interest: Alfredo E. Farjat, Fangfang Liu, Suguru Okami, Satoshi Yamashita, and Nikolaus G. Oberprieler are employees of Bayer, which funded this study. Alain Gay and David Vizcaya were employees of Bayer when this research was conducted. J. Bradley Layton, Ryan Ziemiecki, Catherine B. Johannes, and Anam M. Khan are employees of RTI Health Solutions, which received research funding for this study from Bayer; Manel Pladevall-Vila was an employee of RTI Health Solutions when this research was conducted. This independent research institute performs financially supported studies for government and related healthcare authorities and several pharmaceutical companies. Craig I. Coleman has received grant funding and consulting fees from Bayer AG and AstraZeneca Pharmaceuticals. Michael Walsh is employed by the Ontario Renal Network of Ontario Health; has received grant funding from the Canadian Institutes of Health Research, British Heart Foundation, Medical Research Future Fund, National Health and Medical Research Council (Australia), Health Research Council (New Zealand), Hamilton Academic Health Sciences Organization, Vifor; has received consulting fees for Otsuka, Glaxo-Smith Kline, Bayer, Visterra, Alexion; is a member of steering committees for the Canadian Institutes of Health Research, Medical Research Future Fund, National Health and Medical Research Council (Australia), Bayer, Otsuka; is on data safety monitoring boards for Hansa Pharmaceuticals, National Institute of Health Research (UK), Medical Research Council (UK), Roche; and is a member of event adjudication committees for Novo Nordisk and the Dutch Kidney Foundation. Csaba P. Kovesdy received consulting fees from Abbott, Akebia, Astra Zeneca, Bayer, Boehringer Ingelheim, Cara Therapeutics, CSL Behring, CSL Vifor, GSK, Pharmacosmos, ProKidney, Renibus and Takeda. Yuichiro Yano reports consultancy for Bayer. Naoki Kashihara reports research grants from Daiichi Sankyo, AstraZeneca, and Bayer. Natalie Ebert receives honoraria from Bayer AG. Reimar W. Thomsen has given single lectures on medical research (with and without compensation) for AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Sanofi. Christian Fynbo Christiansen, Reimar W. Thomsen, Ina Trolle Andersen, and Philip Vestergaard Munch are employees of Aarhus University, which receives institutional research funding from public and private entities, including regulators, pharmaceutical companies, and contract research organizations. This includes the present study. Aníbal García-Sempere, Clara Rodríguez-Bernal, Celia Robles Cabaniñas, and Isabel Hurtado are employed by FISABIO, a research body in Spain affiliated with the Health Department of the Valencia Government, which receives public and private funding to conduct biomedical research, including the present study. Ethical Approval: This study used de-identified data from electronic health records. The study was reviewed and approved by the relevant ethics committee for each data source, in accordance with local regulations. Ethics committee review was waived for DNHR. The study protocol was reviewed and approved by the Comité Ético de Investigación con Medicamentos del Hospital Clínico Universitario de Valencia for VID (2022/163). This study protocol was reviewed and approved by the ethics committee of the Shiga University of Medical Science for J-CKD-DB-Ex (R2022-156). Optum EHR data are de‐identified and are compliant with the Health Insurance Portability and Accountability Act of 1996. This study was deemed to not constitute research involving human subjects according to 45 Code of Federal Regulations 46.102(f) and was deemed exempt from board oversight. The institutional review board of RTI International deemed the study exempt from full review. This study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments. Patient consent for participation and patient consent for publication are not applicable, except for J-CKD-DB-Ex, where informed consent was obtained through an opt-out method on the website of participating university hospitals.
