SGLT2 inhibitor therapy in pulmonary hypertension significantly increased beta-hydroxybutyrate (0.32 to 0.54 mmol/L, p<0.001) and decreased lactate, uric acid, BNP, and HbA1c.
Cross-Sectional (n=126)
No
Does SGLT2 inhibitor therapy improve metabolic and biochemical profiles in patients with pulmonary hypertension?
SGLT2 inhibitor therapy in pulmonary hypertension is associated with improved markers of oxygen efficiency and reduced right ventricular strain, suggesting a shift toward ketone-based energy production.
Abstract Rationale Pulmonary hypertension (PH) involves disordered cellular metabolism that limits oxygen use and forces cells to rely on less efficient glucose pathways. This imbalance raises lactate, uric acid, and brain natriuretic peptide (BNP), reflecting oxidative stress and strain on the right ventricle (RV). Sodium glucose cotransporter 2 (SGLT2) inhibitors improve metabolic efficiency in the heart and kidneys and may also benefit the pulmonary circulation by encouraging oxygen-efficient fuel use. This study examined how SGLT2 therapy affects metabolic and biochemical profiles in patients with PH. Methods We performed a cross sectional single center study of adults aged 18 years or older with confirmed World Health Organization Group 1 to 3 PH between 2019 and 2024. Data were collected from the institutional PH registry and hospital laboratory system. Patients who received empagliflozin or dapagliflozin for at least six months were compared with matched PH controls. Continuous variables included beta hydroxybutyrate, lactate, uric acid, HbA1c, and BNP. Group comparisons used unpaired t tests. Statistical significance was defined as p 0.05. Results A total of 126 patients were analyzed (52 SGLT2 users and 74 controls). Mean age was 63 ± 10 years, and two thirds were women. At baseline, 71 percent had elevated lactate (1.8 mmol per L), 65 percent had uric acid above 6 mg per dL, and 78 percent had BNP over 300 pg per mL, indicating tissue hypoxia and oxidative stress. After at least six months of SGLT2 therapy, beta hydroxybutyrate increased from 0.32 ± 0.14 to 0.54 ± 0.16 mmol per L (p 0.001), lactate decreased from 2.0 ± 0.6 to 1.4 ± 0.5 mmol per L (p = 0.002), uric acid fell from 6.3 ± 1.4 to 5.1 ± 1.2 mg per dL (p = 0.01), BNP dropped from 412 ± 138 to 280 ± 115 pg per mL (p = 0.02), and HbA1c declined from 6.3 ± 0.5 to 5.8 ± 0.4 percent (p = 0.01). Interpretation:A rise in beta hydroxybutyrate signals a metabolic shift toward ketone-based energy production, which yields more energy per oxygen molecule and supports RV function under pressure load. Conclusion SGLT2 inhibitor therapy in PH was linked to higher ketone levels, lower lactate and uric acid, and improved markers of oxygen efficiency. These findings suggest restoration of aerobic metabolism and potential improvement in pulmonary vascular and RV performance, warranting prospective validation. This abstract is funded by: None
Bhandari et al. (Fri,) conducted a cross-sectional in Pulmonary hypertension (n=126). SGLT2 inhibitors (empagliflozin or dapagliflozin) vs. Matched PH controls was evaluated on Metabolic and biochemical profiles (beta hydroxybutyrate, lactate, uric acid, HbA1c, and BNP). SGLT2 inhibitor therapy in pulmonary hypertension significantly increased beta-hydroxybutyrate (0.32 to 0.54 mmol/L, p<0.001) and decreased lactate, uric acid, BNP, and HbA1c.