Glyco-metabolic effects of ranolazine. A truly multifaceted drug?

Ranolazine (R) is a non-haemodynamic anti-anginal agent used as adjunctive therapy in patients with chronic coronary heart disease (CHD) whose symptoms are unadequately controlled by conventional treatment. R decreases calcium overload in the ischemic myocytes through the inhibition of late sodium channel current in the myocardium; induces myocardial relaxation and improves myocardial blood flow. In addition to its anti-angina effect, other possible clinical applications of R have also been explored, including treatment of atrial arrhythmias, chronic heart failure and diabetes. With regard to diabetes R has been shown to significantly improve glycemic control in diabetic patients with CHD in post-hoc analysis of large-scale clinical trials. Moreover reduction of glycated hemoglobin and fasting serum glucose levels have been also observed prospectively in small clinical trials conducted on diabetic subjects without CHD by using R alone or in combination with other oral glucose-lowering drugs. Lastly R improved insulin resistance in non-diabetic overweight/obese patients with CHD. Hypothetical mechanisms of this metabolic action are: inhibition of secretion of glucagon from pancreatic islets, preservation of beta cells and increase of insulin delivery to tissues. In light of these observations R appear to be a potential multifaceted drug that offers the opportunity to treat glyco-metabolic disorders alone or in association to CHD. However, prospective studies are too small to be conclusive and new trials are needed to clarify which is the exact role of R in the treatment of glyco-metabolic disorders.