Dapagliflozin in Heart Failure: Congestion Isn't the Gatekeeper

For pharmacists helping manage a patient hospitalized for heart failure (HF), the instinct when adding a new diuresis-supporting agent might be to ease off the loop diuretic. According to David Berg, MD, MPH, principal investigator of the DAPA ACT HF-TIMI 68 trial (NCT04363697) and cardiologist at Brigham and Women's Hospital, the data point the other way—at least at the start.^1,2

"Clinicians should not preemptively back off on the patient's loop diuretic dose in the hospital when starting an sodium-glucose cotransporter 2 (SGLT2) inhibitor," Berg, of the TIMI Study Group, told Pharmacy Times. Instead, he explained, the opportunity to lower loop diuretic doses tends to come later, in the weeks after discharge, as patients improve on therapy.

That practical nuance emerges from a prespecified analysis of DAPA ACT HF-TIMI 68, presented as a late-breaking clinical trial at the European Society of Cardiology (ESC) Congress 2026 in Munich and published simultaneously in JACC: Heart Failure. The analysis found that starting dapagliflozin (Farxiga; AstraZeneca) before a patient hospitalized for HF leaves the hospital produced measurable decongestion within a week, with gains sustained through 2 months.¹

The randomized, double-blind, placebo-controlled trial enrolled 2401 patients hospitalized with a primary diagnosis of HF and elevated natriuretic peptide levels, randomizing them to dapagliflozin 10 mg once daily or placebo after initial clinical stabilization. Compared with placebo, the SGLT2 inhibitor added roughly 1 kg (about 2 pounds) of additional weight loss at 1 week for a given loop diuretic dose—a measure of diuretic efficiency—without a meaningful excess risk of symptomatic hypotension or worsening kidney function.

Berg was also direct about a second point pharmacists may find counterintuitive: volume overload is not a prerequisite for benefit. Although in-hospital dapagliflozin supported early and sustained decongestion, that effect appeared distinct from the therapy's reduction in rehospitalization and death—and baseline congestion severity did not modify the treatment effect. In other words, a patient does not need to be congested to be a candidate.

To unpack what the findings mean for pharmacists supporting inpatient initiation, Pharmacy Times spoke with Berg. His full responses are below.

Pharmacy Times: For a patient being started on dapagliflozin during an HF admission, what should pharmacists prioritize when counseling on expected weight change and volume status in the first week?

David Berg, MD, MPH: In our study, we found that in-hospital initiation led to improvements in multiple complementary measures of volume status within the first week. For a given dose of loop diuretic therapy, adding dapagliflozin produced ~1 kg (~2 pounds) of additional weight loss at 1 week compared to placebo, a measure referred to as diuretic efficiency. Importantly, this augmentation of diuresis was not associated with any meaningful excess risk of symptomatic hypotension or worsening kidney function. So, the key message is that in addition to reducing the risk of rehospitalization and death in the months following discharge, starting an SGLT2 inhibitor in the hospital supports early and continued fluid removal after discharge. Since the amount of additional volume removal tends to be modest, clinicians should not preemptively back off on the patient’s loop diuretic dose in the hospital when starting an SGLT2 inhibitor. Instead, these data tell us that as clinicians follow patients closely after discharge, there may be opportunities to lower the dose of loop diuretic therapy as patients get better on SGLT2 inhibitors, which is what happened in the DAPA ACT HF-TIMI 68 trial.

Pharmacy Times: Given that congestion severity didn't modify the treatment effect, how should pharmacists think about which hospitalized patients are candidates for in-hospital SGLT2 inhibitor initiation?

Berg: Although starting dapagliflozin during hospitalization supported early and sustained decongestion after discharge, this appeared to be unrelated to the benefit of reducing the risk of rehospitalization and death in the early post-discharge period with in-hospital initiation of an SGLT2 inhibitor. In other words, starting an SGLT2 inhibitor like dapagliflozin in patients with heart failure reduces the short- and long-term risk of adverse heart failure outcomes and also promotes optimization of volume status, but you don’t need to be volume overloaded to experience the multiple clinical benefits of this therapy.

REFERENCES

1. Halpern L. In-hospital dapagliflozin speeds decongestion in heart failure. Pharmacy Times. Published September 9, 2026. Accessed September 16, 2026. https://www.pharmacytimes.com/view/in-hospital-dapagliflozin-speeds-decongestion-in-heart-failure

2. Dapagliflozin and effect on cardiovascular events in acute heart failure—thrombolysis in myocardial infarction 68 (DAPA ACT HF-TIMi 68). ClinicalTrials.gov Identifier: NCT04363697. Last Updated June 16, 2026. Accessed September 16, 2026. https://clinicaltrials.gov/study/NCT04363697