Current challenges in the treatment of cardiac fibrosis: Recent insights into the sex-specific differences of glucose-lowering therapies on the diabetic heart: IUPHAR Review 33.

A significant cardiac complication of diabetes is cardiomyopathy, a form of ventricular dysfunction that develops independently of coronary artery disease, hypertension and valvular diseases, which may subsequently lead to heart failure. Several structural features underlie the development of diabetic cardiomyopathy and eventual diabetes-induced heart failure. Pathological cardiac fibrosis (interstitial and perivascular), in addition to capillary rarefaction and myocardial apoptosis, are particularly noteworthy. Sex differences in the incidence, development and presentation of diabetes, heart failure and interstitial myocardial fibrosis have been identified. Nevertheless, therapeutics specifically targeting diabetes-associated cardiac fibrosis remain lacking and treatment approaches remain the same regardless of patient sex or the co-morbidities that patients may present. This review addresses the observed anti-fibrotic effects of newer glucose-lowering therapies and traditional cardiovascular disease treatments, in the diabetic myocardium (from both preclinical and clinical contexts). Furthermore, any known sex differences in these treatment effects are also explored.