Does the drug dapagliflozin benefit hospitalized patients with COVID-19?

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• In hospitalized patients with COVID-19, the SGLT2 inhibitor dapagliflozin was well tolerated regardless of kidney function, but did not significantly lower patients’ risk of organ failure, kidney problems, or death compared with placebo. 

Newswise — Washington, DC (April 28, 2022) — In a recent randomized clinical trial of hospitalized patients with COVID-19 and cardio-metabolic risk factors, the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin did not significantly reduce patients’ risk of organ failure, kidney problems, or death compared with placebo, although numerically fewer participants treated with dapagliflozin experienced these outcomes. The findings are published in CJASN. 

SGLT2 inhibitors have numerous kidney- and heart-protective effects. Because COVID-19 affects multiple organ systems, Hiddo Lambers Heerspink, PhD, PharmD (University of Groningen, the Netherlands) and his colleagues conducted a secondary analysis from the Dapagliflozin in Respiratory Failure in Patients With COVID-19 (DARE-19) trial to assess the efficacy and safety of the SGLT2 inhibitor dapagliflozin in 1,250 patients with cardio-metabolic risk factors acutely hospitalized with COVID-19.

Dapagliflozin was well tolerated regardless of patients’ kidney function, but compared with placebo, it did not result in a significant risk reduction in the primary outcomes of organ dysfunction or death, or improvement in recovery. Dapagliflozin also did not result in a significant risk reduction in the secondary composite kidney outcome of composite of acute kidney injury, kidney replacement therapy, or death.

“These new data from DARE-19 reinforce the safety of dapagliflozin in acutely ill patients hospitalized with COVID-19 even in those with reduced kidney function who are at particularly high risk of acute kidney injury,” said Dr. Heerspink.

An accompanying editorial notes that DARE-19 was a neutral trial for all of the outcomes it assessed, both individually and collectively. “Nevertheless, DARE-19 was a positive trial from the perspective of the safety of using an SGLT2 inhibitor while experiencing acute illness in patients with either preserved or reduced kidney function,” the authors wrote. 

Study authors include Hiddo JL Heerspink, Remo HM Furtado, Otavio Berwanger, Gary G. Koch, Felipe Martinez, Omar Mukhtar, Subodh Verma, Samvel B. Gasparyan, Fengming Tang, Sheryl L Windsor, Vicente Cés de Souza-Dantas, Mildren del Sueldo, Robert Frankel, Ali Javaheri, Rafael A. Maldonado, Caryn Morse, Marco Mota-Gomes, Douglas Shemin, Osvaldo Lourenço Silva Jr., Alexandre Pereira Tognon, Marcel Twahirwa, Joan Buenconsejo, Russell Esterline, Jan Oscarsson, Philip Ambery, Anna Maria Langkilde, and Mikhail N Kosiborod.

Disclosures:

Ambery is an employee and stockholder of AstraZeneca and reports dosing patent for Cotadutide (AstraZeneca drug).

Berwanger reports research funding from Amgen, AstraZeneca, Bayer, BMS, Boehringer-Ingelheim, Novartis, Pfizer, and Servier.

Buenconsejo was an employee and stockholder of AstraZeneca at the time these analyses were conducted and reports other interests or relationships with American Statistical Association and Drug Information Association.

V.C. de Souza-Dantas reports receipt of drugs from AstraZeneca for the conduct of this study.

Esterline is an employee and stockholder of AstraZeneca.

Frankel reports consultancy agreements with AstraZeneca; stock/stock options in Boston Scientific; honoraria from AstraZeneca, Boston Scientific, and Medtronic; serving in a leadership/fiduciary role in the American Medical Association, the Medical Society of the State of New York, and the Empire Foundation; and speakers bureau for AstraZeneca and Medtronic.

R.H.M. Furtado reports research grants from Aché, AstraZeneca, Bayer, Brazilian Ministry of Health, CytoDin, EMS, Pfizer, Servier, University Health Network (received from his institution), and Lemann Foundation Research Fellowship; honoraria from AstraZeneca, Bayer, and Servier; serving in an advisory or leadership role for Biomm; and speakers bureau for AstraZeneca, Bayer, and Servier.

S.B. Gasparyan is an employee and stockholder of AstraZeneca.

H.J.L. Heerspink reports ongoing consultancy agreements with AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, CSL Behring, Dimerix, Fresenius, Gilead, Janssen, Merck, Mundi Pharma, Mitsubishi Tanabe, Novo Nordisk, Retrophin, and Travere Pharmaceuticals; research funding from AbbVie, AstraZeneca, Boehringer Ingelheim, and Janssen research support (grant funding directed to employer); and speakers bureau for AstraZeneca.

Javaheri received research support for this study from AstraZeneca. He has also received a research grant from AstraZeneca to study the effects of dapagliflozin in inflammatory models. He has previously held stock options in Pfizer and DexCom (minor financial interest, not related to this work). He also has three pending patents (not directly related to this work) for the use of fusion protein nanodiscs for the treatment of heart failure, the use of apolipoprotein M to treat macular degeneration, and inhibition of lysosomal lipolysis to treat ischemia. A. Javaheri reports ownership interest in upstart, monday, datadog, aal, tca, exel, four, pfizer, moderna, appian, knsl, fiverr, uipath, docn, shopify, crwd, snow, zs, BA, BaO, appl, vs, nflx, sbux, google, cmg, dis, nvda, tsla, zm, now, pypl, twitter, globus medical, docusign, cerence, UCO, IDXX, chegg, everbridge, fastly, twilio, amazon, wayfair, dominoes, etsy, costco, expedia, global payments, snap, at&T, dexcom, trade desk, bigC, rivian, mtch, csco, jd.com, rdfn, tdoc, lmnd, farfetch, pltr, vygvf, mgni, fubo, lspd, amc, and roku; research funding from AstraZeneca, Castle Biosciences, and Regeneron; honoraria from Castle Biosciences; and three pending patents: fusion protein nanodiscs for treatment of heart failure, lysosomal lipase inhibition, and apolipoprotein M for eye diseases. A. Javaheri's spouse reports consultancy agreements with Castle Biosciences.

G.G. Koch is the principal investigator of a biostatistics grant from AstraZeneca. He is also the principal investigator from biostatistics grants from other biopharmaceutical sponsors that have no relationship to the submitted work. G.G. Koch reports ownership interest in IQVIA; research funding from AbbVie, Acceleron, Amgen, Arena, AstraZeneca, Cytokinetics, Eli Lilly, Gilead Sciences, GSK, HUYA, Johnson & Johnson, Landos Biopharma, Merck, Momentum, Novartis, Oppilan Pharma, Otsuka, Pfizer Inc, Sanofi, UCB, and vTv Therapeutics and serving in an advisory or leadership role for Journal of Biopharmaceutical Statistics, Pharmaceutical Statistics, and Statistics in Medicine.

M.N. Kosiborod reports consultancy agreements with Alnylam,Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Esperion Therapeutics, Janssen, Lexicon, Merck (Diabetes), Novartis, Novo Nordisk, Pharmacosmos, Sanofi, and Vifor Pharma; a research grant for the conduct of this study from AstraZeneca; research funding from AstraZeneca and Boehringer Ingelheim; honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Merck (Diabetes), Novartis, Novo Nordisk, Sanofi, and Vifor Pharma; and serving on the Editorial Boards of JACC and Circulation.

A.M. Langkilde is an employee and stockholder of AstraZeneca.

R.A. Maldonado has received payment/honoraria from AstraZeneca. 

Martinez reports employment with DAMIC INSTITUTE; consultancy agreements with AstraZeneca, Bayer, BMS, Boehringer Ingelheim, and Novartis; research funding from St. Lukes University, Kansas City; honoraria from AstraZeneca, Bayer, BMS, Milestone, and Novartis; personal fees from AstraZeneca during the conduct of the study; serving in an advisory or leadership role for European Cardiology Reviews; and speakers bureau for AstraZeneca, Boehringer Ingelheim, and Novartis.

Morse declares a clinical trial agreement to participate as a study site in this trial. C. Morse reports consultancy agreements with Viiv Healthcare and research funding as clinical trial investigator in COVID studies supported by Moderna, Gilead, Janssen, and Ridgeback Biotherapeutics and as clinical trial investigator in HIV trials supported by Gilead.

Oscarsson is an employee and stockholder of AstraZeneca.

Tang reports employment with Amgen and ownership interest in Amazon, Amgen, CRM, Facebook, Home Depot, and Lowes.

Twahirwa reports speakers bureau for AstraZeneca.

Verma reports research funding from Amarin, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Eli Lilly, HLS Therapeutics, Janssen, Merck, Novo Nordisk, Pfizer, and PhaseBio; speaker honoraria from AstraZeneca, Bayer, Boehringer-Ingelheim, Eli Lilly, EOCI, HLS Therapeutics, Janssen, Merck, Novartis, Novo Nordisk, Pfizer, PhaseBio, Sanofi, Sun Pharmaceuticals, and TKTWG; has received research and/or speaking honoraria from Amarin, Amgen, AstraZeneca, Bayer, CMS, HLS, Janssen, Merck, Novartis, Novo Nordisk, PhaseBio and Sanofi; serving on advisory boards for Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Eli Lilly, HLS Therapeutics, Janssen, Merck, Novartis, Novo Nordisk, and Sanofi; holds the Tier 1 Canada Research Chair in Cardiovascular Surgery; and is the President of the Canadian Medical and Surgical Knowledge Translation Research Group, a federally incorporated not-for-profit physician organization. 

The article, titled “Dapagliflozin and Kidney Outcomes in Hospitalized Patients with COVID-19 Infection: An Analysis of the DARE-19 Randomized Controlled Trial,” will appear online at http://cjasn.asnjournals.org/ on April 28, 2022, doi: 10.102215/CJN.14231021.

The editorial, titled “Learnings from Throwing Paint at the Wall for COVID-19 with an SGLT2 Inhibitor,” will appear online at http://cjasn.asnjournals.org/ on April 28, 2022, doi: 10.2215/CJN.03250322.

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