Effects of SGLT2-Inhibitors on Comprehensive Geriatric Assessment, Biomarkers of Oxidative Stress, and Platelet Activation in Elderly Diabetic Patients with Heart Failure with Preserved Ejection Fraction

Background: Heart failure (HF) with preserved ejection fraction (HFpEF) represents a major comorbidity in the elderly and is associated with cognitive impairment (CoI) and type 2 diabetes mellitus (T2DM). In this context, there is an increase in oxidative stress and platelet activation biomarkers. The aim of this study was to evaluate the effects of 6 months' treatment with SGLT2i on functional, mood-related, and cognitive aspects, assessed by performing a comprehensive geriatric assessment (CGA), and on oxidative stress and platelet activation biomarkers, in a cohort of HFpEF elderly patients with T2DM. We recruited 150 elderly outpatients (mean age 75.8 +/- 7.4 years). Results: At six-month follow-up, there was a significant improvement in MMSE (p < 0.0001), MoCA (p < 0.0001), GDS score (p < 0.0001), and SPPB (p < 0.0001). Moreover, we observed a significant reduction in Nox-2 (p < 0.0001), 8-Isoprostane (p < 0.0001), Sp-Selectin (p < 0.0001), and Gp-VI (p < 0.0001). Considering Delta MMSE as the dependent variable, Delta E/e', Delta Nox-2, Delta HOMA, Delta 8-Isoprostane, and Delta Uricemia were associated for 59.6% with Delta MMSE. When Delta MoCA was considered as the dependent variable, Delta HOMA, Delta E/e', Delta 8-Isoprostane, Delta Nox-2 and Delta Uricemia were associated for 59.2%. Considering Delta GDS as the dependent variable, Delta HOMA, Delta Nox-2, Delta 8-Isoprostane, and Delta Uricemia were associated with 41.6% of Delta GDS variation. Finally, Delta HOMA was the main predictor of Delta SPPB, which was associated with 21.3% with Delta SPPB, Delta 8-Isoprostane, Delta Nox-2, Delta E/e', and Delta Uricemia added another 24.1%. Conclusion: The use of SGLT2i in elderly patients with T2DM and HFpEF significantly contributes to improving CGA scales and biomarkers of OS and PA.