What is the clinical evidence from this study?

Study design: Cohort. Population: Fontan circulatory failure (n=33). Intervention: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) vs. Pre-treatment baseline (1 year prior). Primary outcome: Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) 1 year after starting SGLT2i (-26.5% change, p=0.010).

May 8, 2026Frontiers in Cardiovascular Medicine0 citationsOpen Access

Real-world experience with sodium-glucose cotransporter 2 inhibitors in adults with Fontan circulatory failure

RNRalph M. L. Neijenhuis ACA M Cedars AZAli Zaidi

Key Result

SGLT2 inhibitors significantly reduced NT-proBNP levels by 26.5% in adult patients with Fontan circulatory failure, reversing the prior upward trajectory.

Study Design

Type

Cohort (n=33)

Multicenter

Yes

Structured PICO

Does SGLT2i therapy safely improve NT-proBNP and clinical parameters in adult patients with Fontan circulatory failure?

Population

33 adult patients with Fontan circulatory failure (FCF), median age 32, 51.5% female, including both reduced (33.3%) and preserved (66.7%) ventricular function.

Intervention

Sodium-glucose cotransporter 2 inhibitors (SGLT2i)

Comparator

Historical self-control (patient data from one year prior to SGLT2i initiation)

Outcome

Safety (side effects, treatment discontinuation) and efficacy (longitudinal changes in serum biomarkers and clinical parameters from one year before to one year after SGLT2i initiation)surrogate

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.

Main Result

Effect estimate: -26.5% change

Absolute Event Rate: 200.4% vs 272.6%

p-value: p=0.010

Limitations

Single-arm, retrospective, real-world setup
Anatomical and surgical heterogeneity inherent to the Fontan population
Lack of catheterization data prevented detailed stratification of hemodynamic mechanisms
Creatinine-based eGFR estimation may overestimate actual renal function due to sarcopenia
Functional performance was not evaluated

Abstract

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.

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