Preclinical studies show that the angiotensin II receptor blocker telmisartan has a beneficial effect on metabolic parameters including plasma glucose, insulin resistance and lipid abnormalities, in addition to its proven effect on hypertension, according to data presented during the annual meeting of the European Society of Cardiology.

Telmisartan’s mechanism of action includes partial activation of PPAR-gamma (peroxisome proliferator-activated receptor-gamma) receptors. PPAR-gamma is a hormone receptor known to have an important role in regulating carbohydrate and lipid metabolism by increasing insulin sensitivity.

“These preclinical findings are very exciting and suggest telmisartan (MicardisR) 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.”

Telmisartan is structurally similar to the PPAR-gamma activator, pioglitazone, which has been approved for treatment of type 2 diabetes. Telmisartan partially activates PPAR-gamma resulting in metabolic effects that differentiate it from other angiotensin receptor blockers, according to preclinical data that show a beneficial effect on insulin resistance and blood lipids independent of its effect on the renin-angiotensin-aldosterone system.

“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 telmisartan in the prevention of new onset diabetes and cardiovascular disease.”

Large-scale studies such as HOPE, EUROPA, LIFE and VALUE have shown that angiotensin receptor blockers and angiotensin-converting enzyme inhibitors can reduce new onset diabetes compared to treatment with other older antihypertensive treatments.

The potential effects of telmisartan 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.