DEFENDER
Trial question
What is the role of dapagliflozin in patients with critically illness and acute organ dysfunction?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
47.0% female
53.0% male
N = 507
507 patients (238 female, 269 male)
Inclusion criteria: patients with unplanned ICU admission and presenting with at least one organ dysfunction
Key exclusion criteria: organ dysfunction criteria for > 24 hours; end-stage kidney disease undergoing maintenance dialysis; prior use of dapagliflozin or other SGLT-2 inhibitor; T1DM; diabetic ketoacidosis; planned ICU admission following elective surgery
Interventions
N=248 dapagliflozin (standard care plus 10 mg of dapagliflozin for up to 14 days or until ICU discharge)
N=259 standard care (standard of care for up to 14 days or until ICU discharge)
Primary outcome
Rate of hospital death, initiation of kidney replacement therapy, and shorter intensive care unit length of stay through 28 days
42.3
41.9
42.3 %
31.7 %
21.1 %
10.6 %
0.0 %
Dapagliflozin
Standard
care
No significant
difference ↔
No significant difference in the rate of hospital death, initiation of kidney replacement therapy, and shorter ICU length of stay through 28 days (42.3% vs. 41.9%; WR 1.01, 95% CI 0.9 to 1.13)
Secondary outcomes
No significant difference in death in the hospital (35.5% vs. 34.4%; OR 1.06, 95% CI 0.76 to 1.52)
No significant difference in initiation of kidney replacement therapy (10.9% vs. 15.2%; OR 0.76, 95% CI 0.51 to 1.18)
No significant difference in median days free from ICU (18 days vs. 16.5 days; OR 1.03, 95% CI 0.77 to 1.38)
Safety outcomes
No significant difference in serious adverse events.
Conclusion
In patients with unplanned ICU admission and presenting with at least one organ dysfunction, dapagliflozin was not superior to standard care with respect to the rate of hospital death, initiation of kidney replacement therapy, and shorter ICU length of stay through 28 days.
Reference
Caio A M Tavares, Luciano C P Azevedo, Álvaro Rea-Neto et al. Dapagliflozin for Critically Ill Patients With Acute Organ Dysfunction: The DEFENDER Randomized Clinical Trial. JAMA. 2024 Jun 14. Online ahead of print.
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