Pharmacogenetics of Metformin in Type 2 Diabetes: Perspectives for Latin America

Abstract

Metformin, in the anti-hyperglycemic pharmacological therapy, is consumed by more than 150 million people annually in the world due to its affordable price, safety, and because of considerable pleiotropic effect that has a positive impact on the control of glycemia, insulin resistance, cardiovascular health, and cancer in patients with type 2 diabetes (T2D). Differences in metformin’s effect on glycemic control have been associated with diet, abdominal obesity, years of T2D evolutions, and genetic factors. The Population of Latin America presents an important genetic component of Amerindians that could be explained to some extent in the response to metformin in glycemic control. The most recognized effect of metformin is to inhibit gluconeogenesis hepatica. In recent years, it has been observed to reduce the effect on body mass, positive effects on inflammation, and recently on the intestine with changes in the microbiome that favor suppression of postprandial hyperglycemia. Association studies between genetic variants coding for proteins related to metformin pharmacodynamics have shown different effects on glycemic control in several ethnic groups with European and Asian ancestry, but in Latin America they are scarce or none. Nutrients can interact with metformin favoring or decreasing its anti-hyperglycemic effect, so the diet should be considered.