Effects of empagliflozin on progression of chronic kidney disease: a prespecified secondary analysis from the empa-kidney trial
Natalie Staplin, Richard Haynes, PK Judge, Christoph Wanner, Julie Green, Jonathan Emberson, David Preiss, KJ Mayne, SYA Ng, Emily Sammons, Dandan Zhu, Michael Hill, W. Grant Stevens, Karl Wallendszus, S Brenner, AK Cheung, Zhihong Liu, J Li, LS Hooi, Wenjun Liu, Takashi Kadowaki, Masaomi Nangaku, Adeera Levin, David Z.I. Cherney, Aldo P. Maggioni, Roberto Pontremoli, Rajat Deo, Shinichi Goto, Xavier Rosselló, Katherine R. Tuttle, Dominik Steubl, Michaela Petrini, Siegfried Seidi, Martin Landray, Colin Baigent, WG Herrington, Sharirose Abat, Riaz Rahman, Rizna Abdul Cader, MI Abdul Hafidz, MZ Abdul Wahab, NK Abdullah, Talal Abdulsamad, Masami Abe, Ned Abraham, Sarah Acheampong, P Achiri, JA Acosta, A A Adeleke, Vicki Adell, R Adewuyi-Dalton, Nihad Adnan, A Africano, Mohsen Agharazii, Frank G. Aguilar, A Aguilera, M Ahmad, MK Ahmad, NA Ahmad, NH Ahmad, NI Ahmad, Norazinizah Ahmad Miswan, H Ahmad Rosdi, Iffat Ahmed, Sofia B. Ahmed, Sofia B. Ahmed, Joan Aiello, Alastair Aitken, R AitSadi, Sendogan Aker, S Akimoto, Akinwande A. Akinfolarin, S. Akram, Federico Alberici, Christian Albert, Luke Aldrich, M Alegata, Lacy M. Alexander, S Alfaress, Mohammad Alhadj Ali, A Ali, A Ali, Radica Z. Alicic, Arta Aliu, Ricardo López Almaraz, Rashid Almasarwah, Jussara Carnevale de Almeida, Alessia Aloisi, Laith Al‐Rabadi, Mark Dominik Alscher, Pedro Álvarez, Bader Al-Zeer, M. Ochoa de Olza Amat, Christopher S. Ambrose, Hany Ammar, Yu An, L Andriaccio, K Ansu, A Apostolidi, N. Arai
Abstract
BACKGROUND: Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce progression of chronic kidney disease and the risk of cardiovascular morbidity and mortality in a wide range of patients. However, their effects on kidney disease progression in some patients with chronic kidney disease are unclear because few clinical kidney outcomes occurred among such patients in the completed trials. In particular, some guidelines stratify their level of recommendation about who should be treated with SGLT2 inhibitors based on diabetes status and albuminuria. We aimed to assess the effects of empagliflozin on progression of chronic kidney disease both overall and among specific types of participants in the EMPA-KIDNEY trial. METHODS: with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher. We explored the effects of 10 mg oral empagliflozin once daily versus placebo on the annualised rate of change in estimated glomerular filtration rate (eGFR slope), a tertiary outcome. We studied the acute slope (from randomisation to 2 months) and chronic slope (from 2 months onwards) separately, using shared parameter models to estimate the latter. Analyses were done in all randomly assigned participants by intention to treat. EMPA-KIDNEY is registered at ClinicalTrials.gov, NCT03594110. FINDINGS: <0·0001). INTERPRETATION: Empagliflozin slowed the rate of progression of chronic kidney disease among all types of participant in the EMPA-KIDNEY trial, including those with little albuminuria. Albuminuria alone should not be used to determine whether to treat with an SGLT2 inhibitor. FUNDING: Boehringer Ingelheim and Eli Lilly.