@article{e74ee091050347008a1b24981351ba73,
title = "Use of sodium-glucose cotransporter-2 inhibitors and risk of acute kidney injury in older adults with diabetes: A population-based cohort study",
abstract = "BACKGROUND: Regulatory agencies warn about the risk of acute kidney injury (AKI) after the initiation of sodium-glucose cotransporter-2 (SGLT2) inhibitors. Our objective was to quantify the 90-day risk of AKI in older adults after initiation of SGLT2 inhibitors in routine clinical practice. METHODS: We conducted a populationbased retrospective cohort study in Ontario, Canada, involving adults with diabetes who were aged 66 years or older and who were newly dispensed either an SGLT2 inhibitor or a dipeptidyl peptidase-4 (DPP4) inhibitor in an outpatient setting between 2015 and 2017. We used inverse probability of treatment weighting based on a propensity score to balance the 2 groups on measured baseline characteristics. The primary outcome was 90-day risk of a hospital encounter (i.e., visit to the emergency department or admission to hospital) with AKI, which we defined by a 50% or greater increase in the concentration of serum creatinine from the baseline value or an absolute increase of at least 27 μmol/L after an SGLT2 or DDP4 inhibitor was dispensed. We obtained weighted risk ratios using modified Poisson regression and weighted risk differences using binomial regression. RESULTS: We included 39 094 patients with a median age of 70 (interquartile range 68-74) years in the study. Relative to new use of a DPP4 inhibitor, initiation of a SGLT2 inhibitor was associated with a lower 90-day risk of a hospital encounter with AKI: 216 events in 19 611 patients (1.10%) versus 388 events in 19 483 patients (1.99%); weighted risk ratio 0.79 (95% confidence interval 0.64-0.98). INTERPRETATION: In routine care of older adults, new use of SGLT2 inhibitors compared with use of DPP4 inhibitors was associated with a lower risk of AKI. Together with previous evidence, our findings suggest that regulatory warnings about AKI risk with SGLT2 inhibitors is unwarranted.",
author = "Carina Iskander and Cherney, {David Z.} and Clemens, {Kristin K.} and Dixon, {Stephanie N.} and Ziv Harel and Nivethika Jeyakumar and Eric McArthur and Muanda, {Flory Tsobo} and Parikh, {Chirag R.} and Paterson, {J. Michael} and Navdeep Tangri and Udell, {Jacob A.} and Ron Wald and Garg, {Amit X.}",
note = "Funding Information: Competing interests: David Cherney has received consulting fees or speaking honoraria or both from Bayer, Mitsubishi-Tanabe, Abbvie, BMS, Prometic, Novo-Nordisk, Janssen, Boehringer Ingelheim and Lilly, AstraZeneca, Merck and Sanofi, and has received operating funds from Sanofi, Novo-Nordisk, Janssen, Boehringer Ingelheim and Lilly, AstraZeneca and Merck Jacob Udell has received honoraria for advisory board participation from Amgen, AstraZeneca, Boehringer Ingelheim, Janssen, Merck, Novartis and Sanofi Pasteur, and grant support to his institutions from AstraZeneca. Kristin Clemens has received a Diabetes Canada Junior Investigator Award, sponsored by Astra Zeneca, and has also received speaker fees from Sutherland Global Services Canada ULC. She has attended conferences sponsored by Merck. Chirag Parikh has received consultant fees from Akebia Therapeutics and Genfit Biopharmaceutical, grants from the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute, and other support from Renalytix AI. Navdeep Tangri has received personal fees from AstraZeneca, Otsuka, Janssen, and Boehringer Ingelheim and Lilly, and Tricida, grants from AstraZeneca and Tricida, and other support from Tricida. No other competing interests were declared. Funding Information: Funding: This study was supported by the ICES Western site. ICES is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). Core funding for ICES Western is provided by the Academic Medical Organization of Southwestern Ontario (AMOSO), the Schulich School of Medicine and Dentistry (SSMD), Western University, and the Lawson Health Research Institute (LHRI). Parts of this material are based on data and/or information compiled and provided by the Canadian Institute for Health Information (CIHI). However, the analyses, conclusions, opinions and statements expressed in the material are those of the author(s), and not necessarily those of CIHI. The research was conducted by members of the ICES Kidney, Dialysis and Transplantation team at the ICES Western facility, who are supported by a grant from the Canadian Institutes of Health Research (CIHR). Carina Iskander{\textquoteright}s training is supported by the CIHR Drug Safety and Effectiveness Cross-Disciplinary Training (DSECT) Program Scholarship. Amit Garg was supported by the Dr. Adam Linton Chair in Kidney Health Analytics and a CIHR Clinician Investigator Award. Jacob Udell was supported by a Heart and Stroke Foundation of Canada National New Investigator-Ontario Clinician Scientist Award; Ontario Ministry of Research, Innovation and Science Early Researcher Award, Women{\textquoteright}s College Research Institute and Department of Medicine, Women{\textquoteright}s College Hospital. The opinions, results and conclusions are those of the authors and are independent from the funding sources. No endorsement by ICES, AMOSO, SSMD, LHRI, CIHR or the MOHLTC is intended or should be inferred. Publisher Copyright: {\textcopyright} 2020 Canadian Medical Association. All rights reserved.",
year = "2020",
month = apr,
day = "6",
doi = "10.1503/cmaj.191283",
language = "English (US)",
volume = "192",
pages = "E351--E360",
journal = "CMAJ",
issn = "0820-3946",
publisher = "Canadian Medical Association",
number = "14",
}