Systemic study of selected anti diabetic agents in cancer cachexia

Abstract

newlineCancer cachexia can be defined as a syndrome involving multiple factors and accompanied with muscle loss, fat loss, reduction in the nutritional intake, alterations in the carbohydrate metabolism and progresses along with systemic inflammation. Cancer cachexia is the cause of 1/4th of deaths in cancer patients. The syndrome has its impact on the quality of life (QOL) of patients, it can be explained by loss of body weight leading to weakness, inability to perform daily chores, prone to fatigue and thus low self-esteem negatively affecting the quality of life. The impact on the cardiovascular system is evident by the wasting of cardiac muscles and the development of cardiovascular complications. Carbohydrate alteration is specifically characterized by increased peripheral glucose and the development of insulin resistance in cancer cachexia. Peripheral glucose levels increase due to activation of hepatic gluconeogenesis, activation of glycolysis and decreased utilization of glucose by the host. The abnormalities in insulin production and utilization result in the development of insulin sensitivity. Thus, regulating peripheral glucose levels and insulin sensitivity can serve as potential strategy for the management of cancer cachexia. In the present study, we hypothesize that regulation of altered carbohydrate mechanism can serve as a pharmacological approach for the management of cancer cachexia. Antidiabetic agents regulate peripheral glucose and insulin levels, as observed in diabetic patients. In both cancer and diabetes, inflammation, elevated peripheral glucose levels and insulin resistance are common factors and they serve as link between diabetes and cancer. Anti-cancer activity of many antidiabetic agents is reported. Thus, repurposing of antidiabetic agents can be an effective pharmacological approach in management of cancer cachexia. So we selected metformin a biguanide, teneligliptin and vildagl