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Με την ευγενική χορηγία:

CHIESI HELLAS


SANOFI

TOP TRIALS REVIEW Telmisartan: PPAR-γ Activation and Metabolic Effects

Introduction

Evidence from a range of excellent clinical trials proves that lowering BP with several classes of antihypertensive drugs, including angiotensin II type 1 receptor blockers (ARBs), will reduce the complications of hypertension. ARBs, along with other antihypertensives, are beneficial in reducing stroke, coronary vascular disease and nephropathy in patients with diabetes, and have favourable effects on the progression of diabetic and non-diabetic renal disease. Indeed, clinical trial evidence and guidelines provide compelling indications for the use of ARBs in hypertension, particularly when accompanied by diabetes, heart failure or kidney disease.

However, there is growing evidence that not all ARBs are the same. The metabolic syndrome is characterised by the presence of a group of metabolic risk factors including abdominal obesity, insulin resistance, raised BP, and atherogenic dyslipidaemia. People with the metabolic syndrome are at strong risk for the development of diabetes and CVD. The availability of antihypertensives that have a beneficial effect on insulin resistance and dyslipidaemia would have considerable value in clinical practice. The peroxisome proliferator-activated receptor-(PPAR-) plays an important role in the regulation of carbohydrate and lipid metabolism. Drugs that activate PPAR-are beneficial in improving insulin sensitivity and treating diabetes.

There are currently two full PPAR-agonists approved to treat diabetes, the thiazolidinediones: rosiglitazone and pioglitazone. However, these agents are associated with a number of limiting side effects such as sodium retention, oedema, weight gain and, in at-risk individuals, the induction of congestive heart failure. Telmisartan has also recently been shown to stimulate PPAR-, but because it is a partial agonist, it may not be associated with the same adverse properties of full PPAR-agonists. Such findings have major clinical implications, suggesting that ARBs could have unique potential for the prevention and treatment of diabetes and cardiovascular disease in high-risk populations.

Large clinical trials will eventually be needed to determine whether clinical doses of ARB agents are able to render significant antimetabolic effects in addition to their antihypertensive effects, given that ARB agonism of PPAR-appears to be concentration-dependent. At this early stage, telmisartan appears the most promising in the class because it is associated with more pronounced effects at doses equal to physiologic levels compared with other ARBs. This review accordingly examines the emerging data from preclinical and clinical trials investigating the distinctive metabolic characteristics of telmisartan. Clinical studies are presented in a summarised form to highlight the most important details of each study.

Each summary is evaluated to provide essential information about the objectives, methodology and scientific relevance of the selected study. Underpinning the clinical trials, evidence from preclinical studies which have revealed the unique metabolic properties of telmisartan are also evaluated and summarised. Finally, sources providing a background, such as review articles, are examined and their observations presented. We are sure that physicians will benefit from the expert evaluation of our scientists at ADIS INTERNATIONAL MEDICAL EDITIONS and, also, that the Top Trials Review® will provide clinical support for physician's consultations.

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