Table 1.

A review of the main efficacy of different drugs for insulin resistance and DHD

Category	Mechanisms of action	Effects on cardiac function	Reference
Biguanide	↑ Glu uptake and FA oxidation	↓ Exacerbation of diabetes cardiomyopathy	[99-102]
	↓ NF-κB and inflammatory factors
	↓ Cardiomyocytes and fibroblast LV remodeling
Thiazolidinedione	↑ The sensitivity to insulin and the utilization of glucose	↓ The risk of recurrent MACE, stroke, or myocardial infarction in DHD patients	[103-105]
	↑ Myocardial energy metabolism
	↓ Inflammation, lipid and protein metabolism
	↓ Atherosclerotic plaque volume
GLP-1 receptor agonist	↓ Inflammatory myocardial remodeling	↑ LVEF and 6-minute walk test	[106,107]
	↑ Calcium and cardiac systolic	↓ HF worsening hospitalization rate
	↑ Microcirculation perfusion and angiogenesis	Renal protective effect
Dipeptidyl peptidase-IV inhibitor	↑ IRS2 mRNA and IRS2/PI3K	↓ The occurrence of MACE	[108,109]
	↓ NF-κB	Use of alogliptin and saxagliptin in patients with pre-existing HF is controversial
	=/↑ diastolic function	↓ Risk of hospitalization for HF
SGLT-2 inhibitor	↑ β-Cell and insulin sensitivity	Renal protective effect	[110-113]
	↑ Osmotic diuresis and natriuresis
	↓ Sodium-hydrogen exchanger
	↓ The reabsorption of glucose
	↑ Urinary glucose excretion
Statin	↑ PI3K/Akt/eNOS	↓ The occurrence of adverse cardiovascular events	[114,115]
	↑ AMPK
	↑ LVEF and HR
	↓ Myocardial inflammatory factors
Fibrate	↑ The cardiac PPARα and FoxO1	↑ Cardiac function	[116]
	↑ Myocardial energy metabolism
	↓ Ventricular remodeling
Antiplatelet agent	↑ Islet survival and function	↓ The incidence of CVD and all-cause mortality in DM patients	[117-120]
	↑ Islet transplantation outcomes and insulin gene expression
	↓ Lipid oxidation
Trimetazidine	↑ P38MAPK and Akt;	↑ LVEF	[121]
	↓ Cardiomyocytes apoptosis	↓ The occurrence of adverse cardiovascular events
	↑ Anti-inflammatory and antioxidant capacity
Angiotensin-converting enzyme inhibitor	↓ MAPK and oxidative stress	↓ The incidence of CVD and all-cause mortality in DM patients	[122-124]
	↑ Anti-islet fibrosis, islet β-cell function	↓ Hospitalization rate of HF patients with DM
	Renal protective effect	↓ Proteinuria
Angiotensin receptor blocker	↑ PI3K/Akt/eNOS	↓ Proteinuria	[122,123]
	↓ Oxidative stress	Weaker cardioprotective effect than ACEI
	Renal protective effect
Non-steroidal mineralocorticoid receptor antagonist	↓ Inflammation	↓ The occurrence of MACE	[126-128]
	↓ Specific pro-fibrotic cardiac genes	↓ Risk of hospitalization for HF
	↓ Hypertrophy of cardiomyocytes	Renal protective effect

Symbol ↑ indicates that the activation of pathways or effects and symbol ↓ indicates that the inhibition of pathways or effects.

DHD, diabetes heart disease; Glu, glucose; FA, fatty acid; NF-κB, nuclear factor-κB; LV, left ventricular; IRS2, insulin receptor substrate 2; PI3K, phosphatidylinositol 3-kinase; MACE, major adverse cardiovascular events; GLP-1, glucagon-like peptide 1; LVEF, left ventricular ejection fraction; HF, heart failure; SGLT-2, sodium glucose co-transporter 2; Akt, protein kinase B; eNOS, endothelial nitric oxide synthase; AMPK, AMPactivated kinase; HR, heart rate; PPARα, peroxisome proliferator-activated receptor α; FoxO1, forkhead box protein O1; CVD, cardiovascular disease; DM, diabetes mellitus; MAPK, mitogen-activated protein kinase; ACEI, angiotensin-converting enzyme inhibitor.