Use of Metformin in Patients with Kidney and Cardiovascular Diseases

Abstract

Metformin is an insulin-sensitizing agent with anti-hyperglycemic properties that is widely used for the treatment of type-2 diabetes. The efficacy of metformin in reducing hyperglycemia is well established, and there is emerging evidence that its chronic use is associated with cancer and cardiovascular disease (CVD) risk reduction. While the hypoglycemic properties of metformin are largely attributed to suppression of hepatic glucose production and increases in peripheral tissue insulin sensitivity, the precise mechanism of the hypoglycemic action of metformin remains unclear. There is evidence that metformin use interrupts mitochondrial oxidative stress in the liver and corrects abnormalities of intracellular calcium metabolism in insulin-sensitive tissues (liver, skeletal muscle, and adipocytes) and cardiovascular tissue. However, the use of metformin in patients with kidney disease, a high-risk CVD state, is confounded by confusion regarding appropriate concerns about the development of lactic acidosis in this population. Thus, we will review current evidence on metformin use for improving CVD outcomes and its therapeutic use in kidney disease.