Potential metabolic effects of telmisartan in preliminary studies
Sep 8, 2005 - 1:34:00 AM
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These preclinical findings are very exciting and suggest Micardis® may have a uniquely beneficial metabolic effect. We have effective treatments for some of the individual components of metabolic syndrome, such as high blood pressure, but we need to tackle the different risk factors concurrently, Professor Ted Kurtz, University of California, USA
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By Boehringer Ingelheim,
[RxPG] Preclinical studies show that the angiotensin II receptor blocker (ARB), Micardis® (telmisartan), has a beneficial effect on metabolic parameters including plasma glucose, insulin resistance and lipid abnormalities, in addition to its proven effect on high blood pressure, due to its partial activation of PPAR-gamma (peroxisome proliferator-activated receptor-gamma).1-4 PPAR-gamma is a hormone receptor known to have an important role in regulating carbohydrate and lipid metabolism, by increasing insulin sensitivity.1-5 High blood pressure, lipid abnormalities, insulin resistance and obesity are key components of metabolic syndrome, a common precursor of cardiovascular disease and type 2 diabetes.6 The implications of these findings were discussed today by leading experts at a meeting in Stockholm, Sweden, coinciding with the European Society of Cardiology Annual Meeting.
These preclinical findings are very exciting and suggest Micardis® may have a uniquely beneficial metabolic effect. We have effective treatments for some of the individual components of metabolic syndrome, such as high blood pressure, but we need to tackle the different risk factors concurrently, Professor Ted Kurtz, University of California, USA, commented. These are very early days but given the major impact of the metabolic syndrome on cardiovascular morbidity and mortality, any treatment that could tackle more than one of the components of metabolic syndrome would provide a huge advantage to patients and physicians in the fight against cardiovascular disease.
The Micardis® molecule is structurally similar to the PPAR-gamma activator, pioglitazone,3 which has been approved for the treatment of type 2 diabetes.7 Micardis® partially activates PPAR-gamma resulting in metabolic effects that differentiate it from other ARBs, according to preclinical data.1-4 These data demonstrate that Micardis® has a beneficial effect on insulin resistance and blood lipids, independent of its effect on the renin-angiotensin-aldosterone system (RAAS).1-4
Studies by Schupp et al and Kurtz et al showed Micardis® is a more potent PPAR-gamma activator compared to other commercially available ARBs.1-2 Furthermore, an in vitro and in vivo study reported by Benson et al showed Micardis® significantly reduced serum glucose levels (p<0<0<0
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The implications of these findings were discussed today by leading experts at a meeting in Stockholm, Sweden, coinciding with the European Society of Cardiology Annual Meeting.
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Additional information about the news article
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Telmisartan (Micardis®)
Telmisartan was discovered and developed by Boehringer Ingelheim, Germany. Boehringer Ingelheim markets telmisartan under the trademark Micardis® in 84 countries around the world, including the USA, Japan and major European countries.
Telmisartan is also marketed in some countries by Abbott Laboratories, Bayer AG, GlaxoSmithKline, and Yamanouchi (now Astellas Pharma Inc.).
References:
1 Schupp M et al. Angiotensin 1 receptor blockers induce peroxisome proliferator-activated receptor-gamma activity. Circulation. 2004:2054-2056.
2 Kurtz WT, Pravenec M. Antidiabetic Mechanisms of ACE Inhibitors and AII Receptor Antagonists: Beyond the Renin Angiotensin System. Journal of Hypertension 2004 Dec;22 (12):22532261.
3 Benson S et al. Identification of Telmisartan as a Unique Angiotensin Receptor Antagonist with Selective PPARg-Modulating Activity. Hypertension. 2004;43:993-1002.
4 Clasen R, Schupp M et al. PPAR-gamma-Activating Angiotensin Type-1 Receptor Blockers Induce Adiponectin. Hypertension. 2005;46:137-143.
5 Van Zwieten PA, Mancia G. The Metabolic Syndrome a therapeutic challenge. European Society of Hypertension monograph. 2005.
6 International Diabetes Foundation, http://www.idf.org
7 http://www.actos.com/pi.pdf
8 Vitale C, Rosano G et al. Metabolic effect of telmisartan and losartan in hypertensive patients with metabolic syndrome. Cardiovascular Diabetology. 2005;4:6.
9 Derosa G, Ragonesi PD, Mugellini A, Ciccarelli L, Fogari R. Effects of telmisartan compared with eprosartan on blood pressure control, glucose metabolism and lipid profile in hypertensive, type 2 diabetic patients: a randomized, double-blind, placebo-controlled 12-month study. Hypertension Research. 2004 Jul;27(7):457-64.
10 Yusuf S et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. New England Journal of Medicine. 2000;342:145-53.
11 EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet. 2003;362:782-8.
12 Lindholm LH, Ibsen H, Dahlof B et al. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359:1004-1010.
13 Julius S, Kjeldsen SE, Weber MA et al for the VALUE Trial Group. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet 2004; 363 (9426):2022-2031.
14 The ONTARGET/TRANSCEND Investigators. Rationale, design, and baseline characteristics of 2 large, simple, randomized trials evaluating telmisartan, ramipril, and their combination in high-risk patients: The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (ONTARGET/TRANSCEND) trials. Am Heart J 2004; 148:52-61
15 Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 2002;287(3):356-9
16 Diabetes Atlas, second edition, International Diabetes Federation, 2003.
17 Isomaa B, Almgren P, Tuomi T et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001;24(4):683-9
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