Dapagliflozin for Critically Ill Patients With Acute Organ Dysfunction
Authors: Tavares Caio A. M. , Azevedo Luciano C. P. , Rea-Neto Álvaro , Campos Niklas S. , Amendola Cristina P. , Kozesinski-Nakatani Amanda C. , David-João Paula G. , Lobo Suzana M. , Filiponi Thiago C. , Almeida Guacyra M. B. , Bergo Ricardo R. , Guimarães-Júnior Mário R. R. , Figueiredo Rodrigo C. , Castro Joan R. , Schuler Clewer J. , Westphal Glauco A. , Carioca Ana C. R. , Monfradini Frederico , Nieri Josue , Neves Flavia M. O. , Paulo Jaqueline A. , Albuquerque Camila S. N. , Silva Mariana C. R. , Kosiborod Mikhail N. , Pereira Adriano J. , Damiani Lucas P. , Corrêa Thiago D. , Serpa-Neto Ary , Berwanger Otavio , Zampieri Fernando G. ,   DEFENDER Investigators, Souza Juliano , Sanches Luciana , Castro Maisa , Cunha Mariana , Fagundes Flávia , Siqueira Juan , Westphal Glauco , Ospina Cristian , Silva Evelin , Ramos Juliano , Machado Miriam , Fermamdes Ruthy , Lunardi Camila , Radun Luana , Moura Andervan , Silva Evanio , Dantas Livia , Gomes Livia , Silva Maria Luzia , Nunes Yolanda , Lino Ana Beatriz , Barros Gabrielly , Nunes João Pedro , Barbosa Marivalda , Souza Guilherme , Duarte Hugo , Mota Hannah , Castro Joan , Olambrada Mayler , Borges Rafael , Barros Luciana , Pereira Nelson , Tavares Marcos , Joia Gabriela , Cordeiro Gabriella , Mattos Natalia , Lanza Vinicius , Silva Victoria , Dracoulakis Marianna A , Alvaia Natalia , Vieira Camilla , Freitas Izabela , Conceição Beatriz , Borges Jaqueline , Silva Aline , Caroline Thais , Jesus Josiane , Santos Allan , Vieira Bruno , Guerreiro Isabelle , Oliveira Luciana , Esteves Luiz , Bolini Rodrigo , Carvalho Edmilson , Lacerda Adilson , Ferreira Aline , Sica Gustavo , Oliveira Lara , Guedes Maria das Vitórias , Gebara Otavio , Espirito Santo Ana Paula , Lopes Ana Tarina , Ribeiro Hevelton , Tomba Pablo , Morete Vislaine , Almeida Joyce , Silva Claudia , Gato Luana , Inada Leticia , Dias Claire , Dall’Orto Frederico , Melo Graziela , Silva Ana Roberta , Ribeiro Gislayne , Ferreira Kemilys , Biondi Rodrigo , Ramalho Sergio , Silva Derick , Garbin Eduardo , Pereira Ingrid , Nunes Luana , Lacourt Rayane , Loss Cintia , Silva Jackelyne , Jorge Claudio , Denerdin Graziela , Millani Karla , Machado Luana , Affonso Ana Carolina , Garcia Juliane , Oiafuso Tatiane , Camargo Luana , Morais Kaio , Angeli Aline , Pradela Cassia , Marques Gustava , Silva Joelma , Santos Maria Fernanda , Zini Marina , Candido Keulle , Silva Tamires , Barros Verônica , Pool Mariana , Serra Fabio , Coelho Alef , Vieira Lea , Galvao Tamyres , Tognon Alexandre , Dozza Marcos , Henrich Sabrina , Giordani Andressa , Menegasso Aloma , Antunes Murillo , Gosmano Nicoli , Moura Stefany , Costa Tiberio , Canato Vitoria , Queiroz Gabriela , Gonçalvez Mariana , Zanona Mariana , Dias Hellen , Ferraz Eduardo Bazanelli Junqueira , Rossi Caroline , Pozzo Leandro , Moia Diogo , Soares Ronaldo Vicente Pereira , Marino Ramy Machado , Moreno Bruna Ladeira , Serapião Arthur , Momesso Roberta , Silva Bárbara Gomes da , Santos Cintia Selles , Santos Elaine de Jesus , Sampaio Bruna dos Santos , Piano Luciana Pereira Almeida de 
Published: June 2024

Importance

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors improve outcomes in patients with type 2 diabetes, heart failure, and chronic kidney disease, but their effect on outcomes of critically ill patients with organ failure is unknown.

Objective

To determine whether the addition of dapagliflozin, an SGLT-2 inhibitor, to standard intensive care unit (ICU) care improves outcomes in a critically ill population with acute organ dysfunction.

Design, Setting, and Participants

Multicenter, randomized, open-label, clinical trial conducted at 22 ICUs in Brazil. Participants with unplanned ICU admission and presenting with at least 1 organ dysfunction (respiratory, cardiovascular, or kidney) were enrolled between November 22, 2022, and August 30, 2023, with follow-up through September 27, 2023.

Intervention

Participants were randomized to 10 mg of dapagliflozin (intervention, n = 248) plus standard care or to standard care alone (control, n = 259) for up to 14 days or until ICU discharge, whichever occurred first.

Main Outcomes and Measures

The primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay through 28 days, analyzed using the win ratio method. Secondary outcomes included the individual components of the hierarchical outcome, duration of organ support–free days, ICU, and hospital stay, assessed using bayesian regression models.

Results

Among 507 randomized participants (mean age, 63.9 [SD, 15] years; 46.9%, women), 39.6% had an ICU admission due to suspected infection. The median time from ICU admission to randomization was 1 day (IQR, 0-1). The win ratio for dapagliflozin for the primary outcome was 1.01 (95% CI, 0.90 to 1.13; P = .89). Among all secondary outcomes, the highest probability of benefit found was 0.90 for dapagliflozin regarding use of kidney replacement therapy among 27 patients (10.9%) in the dapagliflozin group vs 39 (15.1%) in the control group.

Conclusion and Relevance

The addition of dapagliflozin to standard care for critically ill patients and acute organ dysfunction did not improve clinical outcomes; however, confidence intervals were wide and could not exclude relevant benefits or harms for dapagliflozin.

Trial Registration

ClinicalTrials.gov Identifier: NCT05558098