Inhibiting angiotensin type 1 receptors as a target for diabetes

Expert Opin Ther Targets. 2008 Oct;12(10):1257-63. doi: 10.1517/14728222.12.10.1257.

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.

Publication types

  • Review

MeSH terms

  • Angiotensin I / metabolism*
  • Angiotensin Receptor Antagonists*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Glucose / metabolism
  • Humans
  • Insulin / metabolism
  • Insulin Resistance
  • PPAR gamma / agonists
  • Receptors, Angiotensin / metabolism

Substances

  • Angiotensin Receptor Antagonists
  • Insulin
  • PPAR gamma
  • Receptors, Angiotensin
  • Angiotensin I
  • Glucose