Telmisartan

Abstract

In 2002, my colleagues and I1 suggested that blockade of the renin-angiotensin system may prevent diabetes by promoting adipogenesis, thereby allowing redistribution of fat from dangerous visceral and ectopic fat deposits to less-dangerous subcutaneous depots. This hypothesis was based on our observation that angiotensin II inhibits human preadipocyte differentiation.2 We subsequently demonstrated increased activity of the renin-angiotensin system in obesity3 and suggested, therefore, that renin-angiotensin blockade should be the treatment of choice in obesity-related hypertension.4 In 2004, Benson et al5 reported the novel observation that the highly lipophilic angiotensin receptor blocker (ARB) telmisartan may directly stimulate the peroxisome proliferator activated receptor γ (PPARγ), a key inducer of adipocyte differentiation. Although this property has since been also reported for irbesartan6 and a losartan metabolite,7 there is no doubt that telmisartan by 1 order of magnitude is the most powerful stimulator of PPARγ activity among the ARBs. Because thiazolidinediones, a class of even more potent PPARγ agonists (“glitazones”), are widely used as insulin sensitizers in the treatment of type 2 diabetes mellitus and promote both adipocyte proliferation and fat redistribution, the report that telmisartan may have similar glitazone-like properties led to widespread and enthusiastic speculations regarding the possible metabolic benefits of this compound. …