Pharmacists who care for patients admitted with heart failure often lower loop diuretic doses when a new agent that supports fluid removal is added. New evidence from the DAPA ACT HF-TIMI 68 trial suggests a different strategy. David Berg, MD, MPH, the trial’s principal investigator, advises against automatically reducing loop diuretic doses at the moment a sodium-glucose cotransporter 2 (SGLT2) inhibitor such as dapagliflozin is started.
The study was presented at the European Society of Cardiology (ESC) Congress 2026 and later appeared in JACC: Heart Failure. It enrolled 2,401 patients who were hospitalized for heart failure and had raised natriuretic peptide levels. After initial clinical stabilization, participants were randomly assigned to receive either dapagliflozin 10 mg once daily or a matching placebo.
Early Decongestion Without Added Risks
Results showed that adding dapagliflozin produced roughly 1 kg (2 pounds) of extra weight loss during the first week compared with placebo. Importantly, this benefit occurred without a rise in symptomatic low blood pressure or a decline in kidney function. The investigators described the phenomenon as “diuretic efficiency,” indicating that the drug improves fluid removal while patients continue their standard loop diuretic regimen.
Berg points out that the chance to lower loop diuretic doses usually appears later, during the outpatient follow-up phase, once patients have responded to the SGLT2 inhibitor.
Congestion Not a Prerequisite for Benefit
The medication lowered the rates of rehospitalization and death, and these effects were independent of how congested patients were at baseline. Berg notes that even individuals who were not markedly volume overloaded experienced the same protective outcomes.
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Separate Mechanisms for Fluid Removal and Outcome Reduction
In-hospital initiation of dapagliflozin produced early and lasting fluid loss, yet this diuretic effect was separate from the drug’s ability to lower rehospitalization and mortality. Analyses showed that patients’ initial level of congestion did not change the magnitude of outcome benefit.
The findings suggest clinicians can start dapagliflozin without assessing fluid overload severity, focusing instead on its proven outcome benefits.
Implications for Clinical Practice
As patients move from the inpatient setting to outpatient care, close monitoring can uncover moments when loop diuretic doses may be safely tapered. This aligns with the trial’s finding that dose reductions are typically considered after patients have shown improvement on the SGLT2 inhibitor.
The DAPA ACT HF-TIMI 68 trial offers clear guidance on the timing and mechanisms of SGLT2-inhibitor therapy in heart failure. By questioning long-standing habits, the study supports a more balanced approach to handling diuresis and volume status in hospitalized individuals.
