A review of pharmacotherapy in type 2 diabetes mellitus and its possible cardiovascular risk

Abstract

Type 2 diabetes mellitus (T2DM) is characterized by multiple pathophysiologic abnormalities. With time, multiple glucose-lowering medications are commonly required to reduce and maintain plasma glucose concentrations within the normal range. T2DM individuals also are at a very high risk for microvascular and macrovascular complications and the incidence of heart attack and stroke is increased two- to three-fold compared with non-diabetic individuals. Nearly 70 % of deaths occur in diabetes due to macrovascular complications, e.g. myocardial infarction, stroke, heart failure and peripheral vascular disease. Therefore, when selecting medications to normalize glucose levels in T2DM patients, it is important that the agent does not aggravate cardiovascular risk factors (CVRFs), and ideally improves and reduces cardiovascular morbidity and mortality. OBJECTIVES: This review article focuses on the following objectives:
• Mechanism of action on different cellular level of oral (Biguanides, Sulfonylureas, Meglitinides, Thiazolidinediones, Dipeptidyl peptidase-4 inhibitors (DPP4i), Sodium glucose linked transporter 2(SGLT2) inhibitors, and Alpha-glucosidase inhibitors) and injectable (Glucagon-like peptide-1(GLP-1) receptor agonists and Insulin) glucose-lowering drugs on established CVRFs and long-term studies of cardiovascular outcomes.
• Correlation between the mechanisms behind the antidiabetic medication and its side effects like weight gain, weight loss, increase or decrease of HDL cholesterol, LDL cholesterol and triglycerides and its effects on cardiovascular system (CVS).
• Correlation between coronary artery disease (CAD) risk factors like Hyperglycaemia, hypertension, vascular inflammatory marker (increased c-reactive protein, increased monocyte chemotactic protein-1, increased proinflammatory cytokines),coagulation and thrombotic markers(like decrease antioxidant status, increased von willebrand factor etc..) and endothelial dysfunctions( decreased vascular reactivity, increased degradation of nitric oxide etc.)
• Selection of different antidiabetic agents based on patient’s physiological conditions and its possible risk factors to prevent CVD(cardiovascular disease)
Keywords: pharmacotherapy, coronary artery disease, type 2 diabetes mellitus, dyslipidemia, vascular inflammation, CVRFs.