442-P: Comparative Study of the Effects of GLP-1 Analog and SGLT2 Inhibitor against Diabetic Cardiomyopathy in Type 2 Diabetic Rats: Possible Underlying Mechanisms

Objectives: In the present study we investigated the possible cardioprotective effects of GLP-1 and SGLTi against diabetic cardiomyopathy (DCM) in type 2 diabetic rats and the mechanisms underlying these effects. Methods: 32- male Sprague Dawley rats were randomly subdivided into 4 equal groups; a) control group, b) DM group, type 2 diabetic rats received 2ml oral saline daily for 4 weeks, c) DM+ GLP-1, type 2 diabetic rats were treated with GLP-1 analogue (liraglutide) at a dose of 75 µg/kg via S.C. injection for 4 weeks and d) DM+ SGLTi: type 2 diabetic rats received SGLT2 inhibitor (dapagliflozin) at a dose of 1mg/kg via oral gastric gavage. By the end of treatment (4 weeks), serum blood glucose, HOMA-IR, insulin and cardiac enzymes (LDH, CK-MB) were measured. Also, the cardiac histopathology, myocardial oxidative stress markers (MDA, GSH and CAT) and norepinephrine (NE), myocardial fibrosis, the expression of caspase-3, TGF-β, TNF-α and tyrosine hydroxylase (TH) in myocardial tissues were measured. Results: T2DM caused significant increase in serum glucose, HOMA-IR index, serum CK-MB and LDH (p Conclusions: GLP-1 and SGLTi exhibited cardioprotective effects against DCM in type 2 diabetic rats. SGLTi showed more cardioprotective effect than GLP-1. The cardioprotective actions of these agents might be due to attenuation of fibrosis, oxidative stress, apoptosis (caspase-3), sympathetic nerve activity and inflammatory cytokines (TNF-α and TGF-β). Disclosure E.A. Eid: None. A. Hussein: None. L. Lashin: None. M. Taha: None.