Diabetes mellitus, a widely prevalent condition across the world has been identified as an independent risk factor for coronary artery disease. Thus, tight glucose control is of utmost importance to reduce morbidity and mortality associated with cardiovascular diseases in patients with diabetes. With regard to this, metformin, an oral hypoglycemic agent has garnered considerable attention due to its cardioprotective properties. Thepleiotropic effects of this drug in blood vessels including endothelial cells, and smooth muscle cells, blood lipids and chronic systemic inflammation may underline its potential role in the prevention and management of cardiovascular disorders such as coronary artery disease.

In atherosclerosis, low-density lipoprotein-cholesterol (LDL-C) plays a key role in enhancing the risk. Thus, it is important to keep the values of this parameter within normal range. It has been reported that with every 38.7 mg/dL reduction of LDL-C, there is a 20% decrease in cardiovascular events. According to an observational study, metformin reduced LDL-C in patients with type 2 diabetes by approximately 11.85 mg/dL. The researchers have unravelled that positive impact of metformin therapy in terms of lowering LDL-C could be one of the possible reasons for its cardioprotective activity.

Furthermore, the inverse link ofhigh-density lipoprotein cholesterol (HDL-C) with the occurrence of cardiovascular events is also well known. Studies conducted in the past have shown that impaired HDL function may increase the risk of atherosclerosis. In addition, decrease in HDL-C efflux may alsobe associated with high risk of atherosclerotic cardiovascular disease. With regard to this, a randomized controlled trial involving 3,070 participants with impaired glucose tolerance demonstrated the efficacy of metformin in improving HDL-C levels. Another study also showed that metformin may help in reducing the risk of atherosclerosis by increasing cholesterol efflux capacity of macrophages.

The researchers have also displayed the role of metformin in reducing major cardiovascular events associated with atherosclerotic cardiovascular disease in type 2 diabetes patients or improving surrogate endpoints like carotid intima-media thickness. A landmark study in this domain, the UK Protective Diabetes Study (UKPDS) randomized 1,704 overweight patients with newly diagnosed type 2 diabetes to receive either conventional treatment with diet alone or with either metformin, sulphonylurea, or insulin. After a median follow up of 10.7 years, it was reported that metformin group had a 36% lower all-cause mortality and a 39% lower risk in the incidence of myocardial infarction than the conventional treatment.

Besides its cardiovascular benefits in diabetic population, it may also be a valuable therapeutic option in non-diabetic patients. A small randomized double-blind placebo-controlled study comprising 33 non-diabetic women demonstrated the efficacy of metformin in reducing myocardial ischemia in women with angina. A subsequent study by Eduardo and coworkers also confirmed that intake of this drug reduced carotid intima-media thickness compared to control group in patients with metabolic syndrome, there by indicating its role in cardioprotection. Based on the currently available data, it can be suggested that metformin appears to be a truly beneficial drug for preventing cardiovascular diseases in patients with and without diabetes mellitus.

Reference

1. Luo F, Das A, Chen J, et al. Metformin in patients with and without diabetes: a paradigm shift in cardiovascular disease management. Cardiovasc Diabetol. 2019;18(1):54.