Association between empagliflozin exposure and skeletal muscle degeneration in patients with heart failure

Abstract Background Sodium–glucose co-transporter 2 inhibitors (SGLT2i) have become essential in the management of heart failure. Their prognostic benefits are consistent across older adults, frail, and underweight patients, but there may be potential adverse effects on the skeletal muscle. Methods In this prospective single-centre observational study, 117 patients with stable congestive heart failure received 10 mg of empagliflozin daily between February 2023 and October 2024. At baseline and again after 6 months, we measured the following nutritional, frailty, and quality-of-life indices (GNRI, CONUT, mini nutritional assessment (MNA), KCCQ-12, Barthel index, clinical frailty scale) and urinary titin N-fragment (U-titin), a biomarker of skeletal muscle degradation. Results After exclusion, 93 patients (median age 79 years; 40% women) were analysed. Baseline U-titin showed weak correlations with GNRI, MNA, and KCCQ-12 scores ( p  p  = 0.017). Conclusions Baseline U-titin levels seem to reflect nutritional and functional status in patients with heart failure. U-titin levels increased during empagliflozin treatment, suggesting a possible association with skeletal muscle degradation.