Diabetes is our fastest growing chronic disease, affecting almost 2 million Australians. Heart failure is a leading cause of death in affected people, with 5-year survival worse than many cancers. Although diabetes-induced heart failure risk is greater in women, our data reveals Australian women with diabetes derive less benefit from current heart failure therapy (particularly a class of drugs called SGLT2 inhibitors) than men. Our most recent evidence suggests that the female diabetic heart exhibits greater fibrosis (or scarring) than males. We hence propose that these sex differences make the female heart more resistant to the protective effects of SGLT2 inhibitors for treating heart failure, and that sex-specific management of heart failure is required in settings of diabetes. A new drug that specifically targets fibrosis, called finerenone, has just been approved for treating Australians with diabetes-induced kidney disease. Clinical trials have suggested that finerenone improves outcomes in people with both diabetes and heart failure. We propose that finerenone, by targeting the exaggerated fibrosis in the female diabetic heart, will offer superior heart failure outcomes than standard care in women with diabetes. Taking advantage of our unique access to cardiac cells derived from men and women with both diabetes and heart failure, we will now demonstrate that finerenone improves diabetic heart failure outcomes in cardiac cell types and in miniature human heart preparations more effectively than standard care. We will specifically determine the relative benefit in females versus males, and whether additive benefits with standard care (SGLT2 inhibitors) are observed. This program will provide new mechanistic insights into the sex-specific impact of these pharmacotherapies in slowing diabetes-induced heart failure progression, taking us one step closer to mechanism-guided, precision medicine for arresting heart failure progression, particularly in women with diabetes.
Last updated15 October 2025