SOGALDI-PEF: SGLT2 inhibitor plus MRA improves biomarker outcomes in HFp/mrEF

The combination of dapagliflozin and spironolactone resulted in improvements in NT-proBNP, eGFR, and serum potassium outcomes, compared with dapagliflozin alone, in patients with heart failure with preserved or mildly reduced ejection fraction (HFp/mrEF).

The SOGALDI-PEF trial (EudraCT 2020-000973-26) compared the safety and efficacy of the combination of the sodium-glucose cotransporter-2 (SGLT2) inhibitor, dapagliflozin, and the mineralocorticoid receptor antagonist (MRA), spironolactone, with that of dapagliflozin alone in 108 patients with HFp/mrEF [1]. The primary outcome of this prospective, randomised trial was NT-proBNP level at 12 weeks.

The combination therapy was associated with a larger reduction in logNT-proBNP than the monotherapy (Δ-0.11; 95% CI -0.22 to -0.01; P=0.035). Furthermore, participants in the combination therapy arm displayed larger reductions in systolic blood pressure (Δ-6.4 mmHg; 95% CI -8.3 to -4.4; P<0.001) and eGFR, as well as a more pronounced increase in serum potassium (see Table). These were secondary efficacy outcomes of the trial. “We did see a higher rate of systolic blood pressure <100 mmHg [8.6% vs 3.8%] and serum potassium >5.5 mmol/L [4.8% vs 0.9%] in the combination arm,” Dr João Ferreira (University of Porto, Portugal) addressed the adverse events in the study. However, the study sample was small and was not powered to evaluate safety outcomes.

Table: Primary and main secondary outcomes of SOGALDI-PEF [1]



eGFR, estimated glomerular filtration rate; SBP, systolic blood pressure; UACR, urine albumin-to-creatinine ratio.

In summary, among patients with HFp/mrEF, compared with dapagliflozin monotherapy, the combination of dapagliflozin plus spironolactone demonstrated a greater NT-proBNP reduction; however, a larger eGFR decrease and serum potassium increase support the need for close monitoring when using the combination therapy. Larger outcome trials are required to test whether such combination therapies improve outcomes. Dr Anne-Christine Ruwald (University of Copenhagen, Denmark) commented that there are still some questions to be answered. “Does the reduction in NT-proBNP result in improved clinical endpoints? And how would the results turn out if spironolactone were replaced by finerenone?” Future trials will have to unravel these issues.

1. Ferreira JP, et al. Sodium glucose cotransporter 2 inhibitor with and without an aldosterone antagonist for heart failure with preserved ejection fraction: SOGALDI-PEF. Hottest trials and trial updates (1), Heart Failure 2025, 17–20 May, Belgrade, Serbia.

Copyright ©2025 Medicom Medical Publishers



Posted on 17 July 202525 August 2025