New antidiabetic drugs’ role in the management of testosterone deficiency and of the cardiovascular disease in hypogonadal diabetic men

Abstract

The known hallmarks of type 2 diabetes mellitus (T2DM), such as hyperglycemia, insulin resistance, visceral adiposity, inflammation, endothelial dysfunction, and oxidative stress, are known to influence the hypothalamus-pituitary-gonadal axis, leading to functional hypogonadism. Both the consequent testosterone (T) deficiency and diabetes are recognized factors influencing cardiovascular (CV) risk. In this context, T replacement therapy showed an improvement in glycemic control and metabolic, anthropometric, and body composition parameters in hypogonadal diabetic individuals. Observational and randomized studies on T replacement therapy suggested the beneficial effect of this treatment on CV risk, although inconclusive results should still be evaluated, particularly when subgroups of patients have to be considered. In this setting, the novel antidiabetic drugs have demonstrated beneficial effects on T levels, due to their positive effects on the hypothalamic–pituitary–gonadal axis, in addition to a proven CV protective action. Thus, the combined metabolic and CV effects of T replacement therapy and novel antidiabetic drugs are of great interest. In this review, we aimed to summarize the present state of the art concerning the association between T deficit and CV risk in diabetic people by analyzing the relationship between endogenous T and CV system in diabetic men. In particular, the impact of novel antidiabetic drugs on male hypogonadism, and the combined cardio-metabolic effects of T supplementation and novel antidiabetic drugs were discussed.