In this episode of The Pharm So Hard Emergency Medicine Podcast, host Jimmy Pruitt, PharmD, BCPS, BCCCP, BCEMP, explores the potential of SGLT2 inhibitors in critically ill patients with guest Daniella Abi Kheir, PharmD. Traditionally viewed as diabetes medications, SGLT2 inhibitors are now gaining attention for their pleiotropic effects, including cardiovascular, renal, and anti-inflammatory benefits. Together, Jimmy and Daniella dive into the DEFENDER trial, the first study to evaluate SGLT2 inhibitors in ICU patients with acute organ dysfunction. They break down the study design, key findings, and practical implications for managing critically ill patients. Could these drugs help prevent renal replacement therapy or improve outcomes in septic patients? The episode also tackles potential safety concerns, including DKA and altered absorption in critically ill populations, while offering actionable insights for clinicians considering SGLT2 inhibitors in the ICU. Tune in for an evidence-based discussion packed with clinical pearls and takeaways.