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Preliminary studies suggest potential metabolic effects of Micardis® (telmisartan)


Furthermore, preclinical studies link the metabolic benefit of the blood pressure lowering medicine Micardis® to its activation of the hormone receptor PPAR-gamma, known to increase insulin sensitivity

Stockholm/Sweden, 6 September 2005 - Preclinical studies show that the blood pressure lowering medicine, Micardis® (telmisartan), has a beneficial effect on metabolic parameters including blood glucose (sugar), insulin resistance and blood lipid (fat) abnormalities due to its partial activation of PPAR-gamma (peroxisome proliferator-activated receptor-gamma).1-4 PPAR-gamma is an hormone (chemical messenger) receptor known to have an important role in stimulating the body’s natural process of regulating carbohydrate and lipid metabolism, by increasing insulin sensitivity.1-5 High blood pressure, blood lipid abnormalities, insulin resistance and central 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.”

Micardis® belongs to the newest class of blood pressure lowering medicines known as angiotensin II receptor blockers, or ARBs. 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 According to preclinical data, the effect of Micardis® on PPAR-gamma results in metabolic effects that differentiate it from other ARBs.1-4 These data demonstrate that Micardis® has a beneficial effect on insulin resistance and blood lipids, independent of its blood pressure lowering effect.1-4

Preclinical studies by Schupp et al and Kurtz et al showed Micardis® is a stronger PPAR-gamma activator compared to other commercially available ARBs.1-2 Furthermore, a study reported by Benson et al, showed Micardis® significantly reduced blood glucose levels and triglycerides (harmful blood lipids) after 5 weeks compared with another ARB, losartan. Insulin levels also tended to be lower in the Micardis® group compared with the losartan group.3

Two independent investigator-led studies have suggested that the partial PPAR-gamma activation of Micardis® may produce metabolic effects of potential clinical relevance, different from other ARBs. A study by Rosano et al of 40 patients showed Micardis® 80mg had greater reductions in blood pressure and greater reductions in blood glucose and insulin resistance in patients over a 3 month treatment period compared to losartan 50mg.8 Furthermore, Derosa et al reported results of a study of 119 patients with type 2 diabetes and mildly raised blood pressure that compared the metabolic effects of Micardis® and another ARB, eprosartan. After 12 months of treatment, patients receiving Micardis® 40mg had a significant reduction in blood pressure and in total cholesterol, triglycerides and LDL (bad) cholesterol compared to patients taking eprosartan 600mg.9

“We now need to investigate these effects further in a large scale trial,” Professor Kurtz concluded. “The ONTARGET Trial ProgrammeTM, which involves over 31,000 patients, will provide further clinical evidence of the potential of Micardis® in the prevention of new onset diabetes and cardiovascular disease.”

Large-scale studies such as HOPE, EUROPA, LIFE and VALUE have shown that ARBs and angiotensin-converting enzyme (ACE) inhibitors can reduce new onset diabetes compared to treatment with other older blood pressure treatments.10-13 The potential effects of Micardis® for the prevention of new onset diabetes and cardiovascular disease are being assessed in the large scale clinical trial, the Ongoing Telmisartan Alone and in combination with Ramipril Global End point Trial (ONTARGET) Trial ProgrammeTM. The first results of the study are expected in 2008.14

About Metabolic Syndrome
Metabolic syndrome is characterised by the clustering of the most dangerous cardiovascular risk factors including central obesity, insulin resistance, high blood pressure and blood lipid abnormalities.6 Nearly a quarter of the world’s population have metabolic syndrome.6,15 Up to 80% of the almost 200 million adults worldwide with diabetes will die of cardiovascular disease.16 People with metabolic syndrome are at increased risk – being twice as likely to die from and three times as likely to have a heart attack or stroke compared to people without the syndrome.17

Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 144 affiliates in 45 countries and nearly 36,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

In 2004, Boehringer Ingelheim posted net sales of 8.2 billion euro while spending nearly one fifth of net sales in its largest business segment Prescription Medicines on research and development.

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.).

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):2253–2261.
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,
8 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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