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 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?


CONCLUSIONS
The Ongoing Telmisartan Alone and in Combination with Ramipril Global End point Trial (ONTARGET) has provided information to answer these questions, and is discussed.
Kintscher
Ulrich
U
Charité-Universitätsmedizin Berlin, Institute of Pharmacology, Center for Cardiovascular Research, Hessische Street, 3-4, 10115 Berlin, Germany. ulrich.kintscher@charite.de
Foryst-Ludwig
Anna
A
Unger
Thomas
T
D000803:Angiotensin I / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D047495:PPAR gamma / Q000819:agonists; D011945:Receptors, Angiotensin / Q000378:metabolism
D057911:Angiotensin Receptor Antagonists; D007328:Insulin; D047495:PPAR gamma; D011945:Receptors, Angiotensin; D000803:Angiotensin I; D005947:Glucose