Mortality reduction among persons with type 2 diabetes: (-)-Epicatechin as add-on therapy to metformin?

Diabetes has become a worldwide epidemic, and is growing at a rapid rate with drastic projections for developing countries. Mexico occupies the ninth place worldwide for type 2 diabetes prevalence, and in the foreseeable future, it is expected rise to the seventh place. Myocardial infarction is the most common cause of death in these patients. Although several drugs are approved for the treatment of type 2 diabetes that reduce factors associated with myocardial infarction, an excess risk of death is still present. In this regard, the American Diabetes Association recommends metformin (oral glucose lowering drug) as the first-line therapy in type 2 diabetic subjects, based on its amply confirmed positive metabolic effects; however, its capacity to reduce cardiovascular mortality in type 2 diabetic subjects is inconclusive. Thus, mortality reduction in these patients has been an elusive goal, and is therefore, imperative to evaluate new pharmacological interventions that may favorably impact mortality in these individuals. On the other hand, epidemiological studies have suggested that moderate consumption of cacao-derived products (i.e., chocolate and cocoa) may reduce the risk of diabetes, myocardial infarction, and cardiovascular disease-associated mortality. Moreover, interventional studies have also suggested that dark chocolate and cocoa consumption is vasculoprotective in normal and type 2 diabetic individuals. (-)-Epicatechin ((-)-EPI) is the main flavanol present in cacao, and suggested to be responsible for the beneficial effects observed after dark chocolate/cocoa consumption. Interestingly, in vivo studies have evidenced the capacity of (-)-EPI to reduce infarct size, and preserve cardiac mechanics in rodent models of ischaemia-reperfusion injury. Nonetheless, long-term studies using (-)-EPI and evaluating its effects on mortality are lacking. Thus, based on their particular properties, it is valid to speculate that (-)-EPI and metformin in conjunction may favorably impact mortality in type 2 diabetic individuals. Here, we provide the evidence that allow us to propose our hypothesis, and further suggest a reasonable way to perform the study needed for such investigation.