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

Int J Mol Sci. 2024 Aug 13;25(16):8811. doi: 10.3390/ijms25168811.

Abstract

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 ΔMMSE as the dependent variable, ΔE/e', ΔNox-2, ΔHOMA, Δ8-Isoprostane, and ΔUricemia were associated for 59.6% with ΔMMSE. When ΔMoCA was considered as the dependent variable, ΔHOMA, ΔE/e', Δ8-Isoprostane, ΔNox-2 and ΔUricemia were associated for 59.2%. Considering ΔGDS as the dependent variable, ΔHOMA, ΔNox-2, Δ8-Isoprostane, and ΔUricemia were associated with 41.6% of ΔGDS variation. Finally, ΔHOMA was the main predictor of ΔSPPB, which was associated with 21.3% with ΔSPPB, Δ8-Isoprostane, ΔNox-2, ΔE/e', and ΔUricemia 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.

Keywords: SGLT2i; T2DM; cognitive impairment; elderly; oxidative stress.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers* / blood
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Dinoprost / analogs & derivatives
  • Dinoprost / blood
  • Female
  • Geriatric Assessment* / methods
  • Heart Failure* / blood
  • Heart Failure* / drug therapy
  • Humans
  • Male
  • Oxidative Stress* / drug effects
  • Platelet Activation* / drug effects
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use
  • Stroke Volume*

Substances

  • Sodium-Glucose Transporter 2 Inhibitors
  • Biomarkers
  • Dinoprost

Grants and funding

This research received no external funding.