Aldosterone antagonism in type 2 diabetes mellitus: a new therapeutic approach to diabetic macrovascular disease?

The renin-angiotensin-aldosterone system has long been a target of pharmacological approaches for the control of blood pressure and increasingly for heart failure, myocardial infarction, nephropathy and diabetes. Clinical trials involving the renin-angiotensin-aldosterone axis have traditionally focused on angiotensin-converting enzyme (ACE) inhibitors or angiotensin (Ang) II receptor blockers, thereby laying the emphasis on inhibiting Ang II. It is now acknowledged that aldosterone is also an important culprit in addition to Ang II. Recently, major intervention trials in heart failure have demonstrated the marked cardiovascular beneficial effect of aldosterone antagonism over and above ACE-inhibitor therapy, underscoring the harmful effects of aldosterone in cardiovascular disease. Diabetes is now increasingly recognised as not only a metabolic disorder but a vascular disease as well. Therefore, the prospect arises that aldosterone antagonism may translate in reduced cardiovascular risk in a high-risk disorder like diabetes mellitus. If so, aldosterone antagonists may offer a new therapy in diabetes mellitus for the primary prevention of cardiovascular disease.