Comparative Cardioprotective Effects of SGLT2 Inhibitors in Preclinical Models of Diabetic Cardiomyopathy
DOI:
https://doi.org/10.64149/J.Ver.8.20s.1-9Keywords:
SGLT2 Inhibitors, Diabetic Cardiomyopathy, Oxidative Stress, Fibrosis, Inflammation, Apoptosis, Sympathetic Nervous System, Type 2 Diabetes, Dapagliflozin, Liraglutide.Abstract
Background: Type 2 diabetes mellitus (T2DM) often leads to severe cardiovascular complications such as diabetic cardiomyopathy (DCM) which is the main cause of significant morbidity and mortality. There is mounting evidence that sodium-glucose cotransporter 2 inhibitors (SGLT2i) offer cardioprotective effects that are not related to glucose-lowering mechanisms.
Objective: We conducted a systematic comparative study to assess the cardioprotective potential of SGLT2 inhibitors (dapagliflozin) versus glucagon-like peptide-1 (GLP-1) agonists (liraglutide) in type 2 diabetic rat models and also to figure out the molecular mechanisms behind this effect.
Methods: Thirty-two male Sprague Dawley rats were divided randomly into four groups: normal controls, untreated T2DM, T2DM + SGLT2i (1 mg/kg), and T2DM + GLP-1 (75 µg/kg) for four weeks. The evaluation was extensive and covered serum biochemistry, cardiac enzymes, myocardial oxidative stress markers (malondialdehyde, glutathione, catalase), inflammatory cytokine mRNA (TNF-α, TGF-β), apoptotic markers (caspase-3), sympathetic nervous system activity (norepinephrine, tyrosine hydroxylase), and histopathology.
Results: Treatment with SGLT2 inhibitor resulted in better glycemic control (95.9% blood glucose reduction) and stronger cardioprotection as compared to GLP-1 therapy. The SGLT2i group vigorously decreased myocardial oxidative stress (63.2% MDA reduction, 82.2% GSH restoration), inflammatory cytokines (69% TNF-α reduction, 73.3% TGF-β reduction), apoptosis (83.6% caspase-3 reduction), myocardial fibrosis (85% reduction), and sympathetic activity (63.3% norepinephrine reduction). The histopathological study showed almost normal myocardial structure with very little fibrosis in the hearts of the animals treated with SGLT2i as compared to the presence of fibrosis in those treated with GLP-1.
Conclusions: The results of this study show that SGLT2 inhibitors have greater cardioprotective efficacy against diabetic cardiomyopathy and that the mechanisms are glucose-independent and involve oxidative stress attenuation, anti-inflammatory effect, apoptosis inhibition, fibrosis suppression, and sympathetic nervous system modulation. These results position SGLT2 inhibitors as powerful cardioprotective drugs with a possible use in the clinic for the prevention of heart failure progression in type 2 diabetic populations.
