Ulrich Kintscher1, Anna Foryst-Ludwig, Thomas Unger. 1. Charité-Universitätsmedizin Berlin, Institute of Pharmacology, Center for Cardiovascular Research, Hessische Street, 3-4, 10115 Berlin, Germany. ulrich.kintscher@charite.de
Abstract
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 PPARgamma. 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 PPARgamma-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.
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 PPARgamma. 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 diabeticpatients? Secondly, is an ARB with PPARgamma-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.
Authors: Martina Winkler; Johanna Schuchard; Ines Stölting; Florian M Vogt; Jörg Barkhausen; Christoph Thorns; Michael Bader; Walter Raasch Journal: Br J Pharmacol Date: 2016-03-27 Impact factor: 8.739