SGLT2 inhibitors significantly reduced NT-proBNP levels by 26.5% in adult patients with Fontan circulatory failure, reversing the prior upward trajectory.
Cohort (n=33)
Yes
Does SGLT2i therapy safely improve NT-proBNP and clinical parameters in adult patients with Fontan circulatory failure?
SGLT2 inhibitors appear safe and are associated with significant reductions in NT-proBNP in adult patients with Fontan circulatory failure, offering a potential novel pharmacological therapy for this population.
Effect estimate: -26.5% change
Absolute Event Rate: 200.4% vs 272.6%
p-value: p=0.010
Background Patients with Fontan physiology frequently develop Fontan circulatory failure (FCF), but there are no evidence-based pharmacological treatment options. Objectives This study evaluated the safety and efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in FCF. Methods A real-world, multicenter study of all adult FCF patients included in the international ACHIEVE-SGLT2i registry (NCT06932081) was conducted. Data on side effects, treatment discontinuation, and clinical outcomes were collected. Longitudinal changes in serum biomarkers and clinical parameters from one year before to one year after SGLT2i initiation were evaluated using linear mixed models. Responses between patients with reduced (FCFrEF) vs. preserved ventricular function (FCFpEF) were compared. Results Thirty-three FCF patients were started on SGLT2i between January 2017 and October 2024. The median age was 32 20.5–42 years, 17 (51.5%) were female, 11 (33.3%) had FCFrEF, and 22 (66.7%) FCFpEF. Over a median follow-up of 8.0 3.2–12.2 months, 5 (15.2%) patients reported side effects, of whom 3 (9.1%) permanently discontinued SGLT2i. There were 11 FCF-related hospitalizations in the year before SGLT2i and 7 during follow-up in 9 patients. Blood pressure and renal function remained stable. NT-proBNP increased from 186.3 116.8–297.1 to 272.6 180.7–411.3 ng/L in the year before treatment (+46.4%, p = 0.022). In the year after starting SGLT2i, NT-proBNP levels decreased significantly to 200.4 126.5–317.4 ng/L (−26.5%, p = 0.010), in both FCFrEF and FCFpEF patients. Conclusions SGLT2i were safe and well-tolerated in adult patients with FCF. SGLT2i treatment was associated with a reduction in NT-proBNP, regardless of FCF phenotype. Clinical Trial Registration ClinicalTrials.gov , identifier NCT06932081.
Neijenhuis et al. (2026) conducted a cohort in Fontan circulatory failure (n=33). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) vs. Pre-treatment baseline (1 year prior) was evaluated on Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) 1 year after starting SGLT2i (-26.5% change, p=0.010). SGLT2 inhibitors significantly reduced NT-proBNP levels by 26.5% in adult patients with Fontan circulatory failure, reversing the prior upward trajectory.