Potential Metabolic Effects of Micardis (Telmisartan)

Micardis has a beneficial effect on insulin resistance, blood sugars, and blood lipids, independent of its effect on the blood pressure. Preclinical studies show that the angiotensin II receptor blocker (ARB), Micardis(R) (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

The hormone receptor PPAR-gamma is 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 last week by leading experts at a meeting in Stockholm, Sweden, coinciding with the European Society of Cardiology (ESC) 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 <.01) and serum triglycerides (p<0.05) after 5 weeks compared with another ARB, losartan. Serum insulin levels also tended to be lower in the Micardis group compared with the losartan group (P <.09).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 80 mg 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 mild hypertension that compared the metabolic effects of Micardis and eprosartan. After 12 months of treatment, patients receiving Micardis 40mg had a statistically significant reduction in blood pressure and in total cholesterol, triglycerides and LDL cholesterol compared to patients taking eprosartan 600 mg. 9

“We now need to investigate these effects further in a large scale trial,” Professor Kurtz concluded. “The ONTARGET Trial Programme(TM), 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.”

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 Programme(TM). The first results of the study are expected in 2008.14

Telmisartan is also marketed in some countries by Abbott Laboratories, Bayer AG, GlaxoSmithKline, and Yamanouchi (now Astellas Pharma Inc.).

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