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CHIESI HELLAS


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Telmisartan improves insulin sensitivity in nondiabetic patients with essential hypertension

Ralf A. Benndorf4, Tanja Rudolph, Daniel Appel, Edzard Schwedhelm, Renke Maas, Friedrich Schulze, Elisabeth Silberhorn, Rainer H. Bfger

Institute of Experimental and Clinical Pharmacology and Toxicology, Department of Clinical Pharmacology, University Hospital Hamburg-Eppendorf, D-20246 Hamburg, Germany Received 18 January 2006; accepted 18 April 2006

Abstract

Hypertension is a cardiovascular risk factor commonly associated with insulin resistance, the metabolic syndrome, and type 2 diabetes mellitus. Recent in vitro data indicate that certain angiotensin receptor antagonists, for example, telmisartan,  activate peroxisome proliferator–activated receptor c (PPAR-c) and increase adiponectin protein content in adipocytes. By this  means, they may improve insulin sensitivity in vivo. To investigate the effect of antihypertensive treatment on insulin  sensitivity and fasting adiponectin serum levels, 37 nondiabetic patients with essential hypertension were randomized to  receive telmisartan, the calcium channel blocker nisoldipine, or their combination for 6 weeks in a prospective, parallel group  study.

Fasting serum glucose, insulin, and adiponectin were evaluated before, 3 weeks (low dose), and 6 weeks (high dose)  after initiation of treatment. Furthermore, the effect of telmisartan on PPAR-c receptor activity was investigated in vitro using a PPAR-c reporter   gene assay. As reported previously, telmisartan significantly enhanced PPAR-c receptor activity in vitro. At baseline, a positive  correlation between insulin serum levels and body mass index of investigated subjects was observed, whereas body mass index   and serum adiponectin levels were negatively associated. High-dose treatment with telmisartan but not with nisoldipine reduced  serum insulin levels as well as the homeostasis model assessment of insulin resistance, but did not affect serum adiponectin  levels.

In conclusion, in our study cohort of nondiabetic patients with essential hypertension, telmisartan improved insulin sensitivity by mechanisms apparently not involving adiponectin induction. Future studies will demonstrate whether these  telmisartan-induced effects may contribute to a blood pressure–independent reduction in cardiovascular morbidity.

D 2006 Elsevier Inc. All rights reserved.

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