Findings from recent randomized clinical trials have established that sodium-glucose cotransporter-2 inhibitors (SGLT2i) improve clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF).1-3 The Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial demonstrated that dapagliflozin significantly reduces the composite end point of a first heart failure (HF) hospitalization, urgent HF visit, or cardiovascular mortality among patients with HFrEF.1 The clinical benefits were similar irrespective of the presence or absence of type 2 diabetes and incremental to background medical therapy. The Empagliflozin Outcome Trial in Patients With Chronic HFrEF (EMPEROR-Reduced) and the Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post Worsening HF (SOLOIST-WHF) trials also demonstrated comparable clinical benefits.2,3 These landmark trial data provide compelling evidence for the addition of SGLT2i as a new pillar of foundational therapy for HFrEF. Yet, while these randomized clinical trials have established remarkable benefits and reasonable safety of SGLT2-i in HFrEF, questions remain regarding the optimal timing of the initiation of this newer therapy compared with other established HFrEF medications.