Dapagliflozin for Critically Ill Patients With Acute Organ Dysfunction: The DEFENDER Randomized Clinical Trial

Area of Science:

• Critical Care Medicine
• Nephrology
• Cardiology
• Endocrinology

Background:

• Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are established treatments for type 2 diabetes, heart failure, and chronic kidney disease.
• The efficacy of SGLT-2 inhibitors in critically ill patients with acute organ dysfunction remains undetermined.

Purpose of the Study:

• To evaluate the impact of dapagliflozin, an SGLT-2 inhibitor, on clinical outcomes in critically ill patients experiencing acute organ dysfunction.
• To assess whether standard intensive care unit (ICU) care plus dapagliflozin improves patient outcomes compared to standard care alone.

Main Methods:

• A multicenter, randomized, open-label clinical trial involving 507 critically ill patients with at least one organ dysfunction (respiratory, cardiovascular, or kidney).
• Participants received either 10 mg of dapagliflozin plus standard ICU care or standard care alone for up to 14 days or until ICU discharge.
• The primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay, analyzed using the win ratio method.

Main Results:

• The addition of dapagliflozin did not significantly improve the primary composite outcome, with a win ratio of 1.01 (95% CI, 0.90-1.13; P=.89).
• A secondary analysis showed a higher probability of benefit for dapagliflozin regarding the use of kidney replacement therapy (10.9% vs 15.1%).
• Confidence intervals for the primary outcome were wide, precluding definitive conclusions about potential benefits or harms.

Conclusions:

• Dapagliflozin, when added to standard care, did not demonstrate a significant improvement in clinical outcomes for critically ill patients with acute organ dysfunction.
• The wide confidence intervals indicate uncertainty regarding the true effect of dapagliflozin in this population.
• Further investigation is warranted to clarify the role and safety of SGLT-2 inhibitors in critical care settings.