Inhibiting angiotensin type 1 receptors as a target for diabetes

Background: Angiotensin type 1 (AT1) receptor blockers (ARBs) are used to treat hypertension and related end-organ damage. ARBs have been recognised as regulators of glucose- and lipid metabolism. Clinical trials demonstrated that AT1 receptor antagonism lowers the risk for type 2 diabetes compared with other antihypertensive therapies. Blockade of AT1 receptors reduces cardiovascular morbidity and mortality in diabetic subpopulations. The mechanisms of the insulin-sensitizing/anti-diabetic effect are not fully understood, and may involve AT1 receptor-dependent pathways and 'pleiotropic' actions of ARBs including activation of insulin-sensitising PPAR gamma. Objective: In clinical practice questions about AT1 receptor blockade in diabetes have to be answered. Firstly, is selective AT1-receptor blockade superior to ACE inhibition in preventing diabetes and reducing cardiovascular end points in diabetic patients? Secondly, is an ARB with PPAR gamma-activating properties superior to one without this action? Results/conclusion: The Ongoing Telmisartan Alone and in Combination with Ramipril Global End point Trial (ONTARGET) has provided information to answer these questions, and is discussed.