The Study About Effect And Mechanism Of Liraglutide And Dapagliflozin On Cardiac Function In Type 2 Diabetic Patients

ObjectiveDiabetic cardiomyopathy is an important complication leading to heart failure and death in patients with diabetes.GLP-1 receptor agonists and SGLT2 inhibitors are two new anti-diabetic agents with cardioprotective effect.The purpose of this study is to evaluate the effects of Liraglutide and Dapagliflozin on cardiac function in patients with T2 DM,and to explore the potential mechanism of the cardioprotective effect of liraglutide in diabetic mice.MethodsPatients with T2 DM from the Metabolic Diseases Hospital of Tianjin Medical University were selected as the research objects and divided into the Liraglutide study group and the Dagagliflozin group according to different inclusion and exclusion criteria.The patients in the Liraglutide study group were randomly assigned to receive liraglutide or glargine insulin,while the others in the Dagagliflozin group were randomly assigned to receive Dagagliflozin or acarbose for 24 weeks.The effects of Liraglutide and Dapagliflozin on the cardiac function were assessed by cardiac magnetic resonance imaging.T2 DM mice models were established to explore the cardioprotective mechanism of Liraglutide.After 8 weeks,the hearts were isolated for histological analysis through Masson’s staining and transmission electron microscopy;the MDA kit were used to detect lipid peroxidation;RT-PCR and Western blot was used to detect tissue m RNA and protein expression levels.Results1.9 patients were randomized to liraglutide and 8 to glargine insulin.As compared with baseline,Liraglutide signifcantly increassed EF、SV、SVI、CO、CI、E and Edec while reduced ESV、LVMI、MVR and T1(P<0.05).In addition,liraglutide reduced DBP、weight、BMI、TC、LDL and increased HDL-C(P<0.05).FBG、P2BG、Hb A1 c levels were improved in both two groups.2.8 patients were randomized to dagagliflozin and 7 to acarbose.As comparedwith baseline,dagagliflozin signifcantly increassed E、E/A and Edec while reduced EDV、EDVI(P<0.05).In addition,dagagliflozin reduced SBP、weight and BMI(P<0.05).FBG、P2BG、Hb A1 c levels were improved in both two groups.3.There are significant changes in myocardial fibrosis in DM mice,relatived to NC group.Treatment with liraglutide for 8 weeks significantly reduced fibrotic tissue formation.Relative to NC group,expression of TFR1,FTL and PTGS2 was enhanced and MDA levels was increased while expression of GPX4 and x CT was reduced in DM group.Liraglutide reversed all parameters measured.Conclusions1.Liraglutide improves the cardiac diastolic and systolic function,inhibits the ventricular remodeling and attenuates cardiac interstitial fibrosis in patients with T2 DM.In addition,liraglutide also has benefits on reducing Hb A1 c,weight,blood pressure and lipid profile,thereby improves the metabolic disorders in T2 DM patients.Liraglutide improves cardiac fibrosis and protects cardiomyocytes from ferroptosis in T2 DM mice model,associated with regulating iron homeostasis and the expression of GPX4 and x CT.2.Dagagliflozin improves cardiac diastolic function in patients with T2 DM,and also has positive effects on reducing Hb A1 c,weight and blood pressure.