Early SGLT2 inhibitor treatment improves diuresis and outcomes in acute HF

In an individual patient-level meta-analysis, early initiation of SGLT2 inhibitors in patients hospitalized with acute HF increased diuresis and reduced the risk of all-cause mortality or HF rehospitalization at 60 days compared with placebo/control, with a favorable cardiorenal safety profile.

This summary is based on the publication of Zonneveld LEEC, ter Maaten JM, Voors AA, et al. - Early effects of SGLT2 inhibitors in acute heart failure: an individual patient-level meta-analysis. Eur J Heart Fail. 2026 Jun 23:xuag184. [Online ahead of print]. doi: 10.1093/ejhf/xuag184.

Introduction and methods

Background

Acute HF is characterized by the onset or progression of congestion, for which loop diuretics are the cornerstone of treatment [1-2]. However, complete decongestion is frequently not achieved [3]. Although SGLT2 inhibitors are established therapy for chronic HF [4-5], their early effects on decongestion in patients hospitalized with acute HF remain uncertain.

Aim of the study

The investigators performed an individual patient-level meta-analysis to evaluate the effects of early SGLT2 inhibitor initiation on diuresis, natriuresis, in-hospital outcomes, and post-discharge clinical outcomes in patients hospitalized with acute HF.

Methods

Individual patient data were pooled from six randomized controlled trials comparing empagliflozin or dapagliflozin with placebo, standard care, or control in patients with acute (decompensated) HF. In total, 623 patients were included, of whom 314 were randomized to an SGLT2 inhibitor. Median age was 67 years, 38% were women, median LVEF was 35%, and 76% had a history of HF. Study medication was started on the day of admission in 64% of patients and within 48 hours in 93% of patients.

Outcomes

The primary endpoint was cumulative 24-hour diuresis. Secondary endpoints included cumulative diuresis up to 5 days, natriuresis, weight change, renal safety, all-cause mortality, HF rehospitalization at 30 and 60 days, and a hierarchical win-ratio analysis incorporating death, HF rehospitalization, and 24-hour diuresis.

Main results

• Patients treated with an SGLT2 inhibitor had significantly greater urine output during the first 24 hours compared with placebo/control (3500 mL vs. 2700 mL; adjusted between-group difference: 604 mL; 95%CI: 340–890; P<0.001).
• The improvement in cumulative diuresis persisted through day 5:
  • 48 hours: +1326 mL (P<0.001).
  • 72 hours: +1605 mL (P<0.001).
  • 96 hours: +2150 mL (P<0.001).
  • 120 hours: +2006 mL (P=0.007).
• Natriuresis did not differ significantly between treatment groups at any measured time point.
• Weight loss became significantly greater with SGLT2 inhibitors at day 5 (−4.65 kg vs. −4.0 kg; P=0.012).
• During the first 5 days, there were no significant differences in NT-proBNP reduction, length of hospital stay, or in-hospital mortality.
• At 60 days, the composite of all-cause mortality or HF rehospitalization was significantly reduced with SGLT2 inhibitors (adjusted HR: 0.62; 95%CI: 0.41–0.95; P=0.028).
• At 30 days, the composite endpoint showed a favorable trend but did not reach statistical significance (adjusted HR: 0.64; 95%CI: 0.40–1.02; P=0.061).
• The hierarchical win-ratio analysis favored SGLT2 inhibitors over placebo/control (win ratio: 1.45; 95%CI: 1.16–1.82; P=0.001).
• SGLT2 inhibitor treatment was not associated with a change in kidney function or worsening renal function and was associated with a lower incidence of hypokalaemia at days 2 and 3 compared with placebo/control.

Conclusion

In this individual patient-level meta-analysis of patients hospitalized with acute HF, early initiation of SGLT2 inhibitors on top of standard diuretic therapy increased diuresis without affecting natriuresis and reduced the risk of all-cause mortality or HF rehospitalization at 60 days compared with placebo/control. Early SGLT2 inhibitor initiation also showed a favorable cardiorenal safety profile. These findings support the early initiation of SGLT2 inhibitors during hospitalization for acute HF.

Find this article online at Eur J Heart Fail.

References

1. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) with the special contribution of the heart fail ure association (HFA) of the ESC. Eur Heart J 2021;42:3599–726. https://doi.org/10. 1093/eurheartj/ehab368
2. Mullens W, Damman K, Harjola V, Mebazaa A, Brunner-La Rocca H, Martens P, et al. The use of diuretics in heart failure with congestion—a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2019;21:137–55. https://doi.org/10.1002/ejhf.1369
3. Valente MAE, Voors AA, Damman K, Van Veldhuisen DJ, Massie BM, O’Connor CM, et al. Diuretic response in acute heart failure: clinical characteristics and prognostic sig nificance. Eur Heart J 2014;35:1284–93. https://doi.org/10.1093/eurheartj/ehu065
4. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2023 fo cused update of the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2023;44:3627–39. https://doi.org/10.1093/eurheartj/ehad195
5. Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med 2020;383:1413–24. https://doi.org/10.1056/NEJMoa2022190