Dapagliflozin vs. metolazone in heart failure resistant to loop diuretics

Eur Heart J. 2023 Aug 14;44(31):2966-2977. doi: 10.1093/eurheartj/ehad341.


Background and aims: To examine the decongestive effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin compared to the thiazide-like diuretic metolazone in patients hospitalized for heart failure and resistant to treatment with intravenous furosemide.

Methods and results: A multi-centre, open-label, randomized, and active-comparator trial. Patients were randomized to dapagliflozin 10 mg once daily or metolazone 5-10 mg once daily for a 3-day treatment period, with follow-up for primary and secondary endpoints until day 5 (96 h). The primary endpoint was a diuretic effect, assessed by change in weight (kg). Secondary endpoints included a change in pulmonary congestion (lung ultrasound), loop diuretic efficiency (weight change per 40 mg of furosemide), and a volume assessment score. 61 patients were randomized. The mean (±standard deviation) cumulative dose of furosemide at 96 h was 977 (±492) mg in the dapagliflozin group and 704 (±428) mg in patients assigned to metolazone. The mean (±standard deviation) decrease in weight at 96 h was 3.0 (2.5) kg with dapagliflozin compared to 3.6 (2.0) kg with metolazone [mean difference 0.65, 95% confidence interval (CI) -0.12,1.41 kg; P = 0.11]. Loop diuretic efficiency was less with dapagliflozin than with metolazone [mean 0.15 (0.12) vs. 0.25 (0.19); difference -0.08, 95% CI -0.17,0.01 kg; P = 0.10]. Changes in pulmonary congestion and volume assessment score were similar between treatments. Decreases in plasma sodium and potassium and increases in urea and creatinine were smaller with dapagliflozin than with metolazone. Serious adverse events were similar between treatments.

Conclusion: In patients with heart failure and loop diuretic resistance, dapagliflozin was not more effective at relieving congestion than metolazone. Patients assigned to dapagliflozin received a larger cumulative dose of furosemide but experienced less biochemical upset than those assigned to metolazone.

Trial registration: ClinicalTrials.gov Identifier: NCT04860011.

Keywords: Dapagliflozin; Diuretic resistance; Heart failure; Metolazone; Sodium-glucose cotransporter 2 inhibitor; Thiazide.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diuretics / therapeutic use
  • Furosemide / therapeutic use
  • Heart Failure* / chemically induced
  • Heart Failure* / drug therapy
  • Humans
  • Metolazone* / adverse effects
  • Metolazone* / therapeutic use
  • Sodium
  • Sodium Potassium Chloride Symporter Inhibitors / therapeutic use


  • Metolazone
  • Sodium Potassium Chloride Symporter Inhibitors
  • Furosemide
  • Diuretics
  • Sodium

Associated data

  • ClinicalTrials.gov/NCT04860011