The
metabolic syndrome is characterized by the clustering of
insulin resistance,
dyslipidemia, and
hypertension and is associated with increased risk of
cardiovascular disease and
type 2 diabetes mellitus. However, older
antihypertensive agents such as
thiazide diuretics and beta-blockers have potentially adverse effects on
glucose and lipid metabolism and may even the exacerbate the
metabolic syndrome and increase risk of
type 2 diabetes. Recent clinical trials have suggested that
antihypertensive agents that inhibit the renin-angiotensin system may reduce risk for new-onset
type 2 diabetes, but only a few of these studies were placebo controlled, and in most cases, the absolute
antidiabetic effects were relatively modest. Evidence is accumulating that
telmisartan, in addition to blocking the
angiotensin II type 1 receptor, activates the
peroxisome proliferator-activated receptor (
PPAR)-gamma a well-known target for treatment of the
metabolic syndrome and diabetes. By contrast, other
angiotensin-receptor blockers are largely devoid of activity on
PPAR-gamma.
Telmisartan is a partial agonist of
PPAR-gamma and has a superior tolerability profile without causing the fluid retention and
edema associated with full agonists of
PPAR-gamma such as
pioglitazone and
rosiglitazone. Recent studies have indicated that in addition to
antidiabetic properties,
PPAR-gamma activators may also provide protection against
atherosclerosis and coronary events. Thus, the ability of
telmisartan both to activate
PPAR-gamma and to block the
angiotensin receptor may provide added value not only in the treatment of the
metabolic syndrome and prevention of
type 2 diabetes but also in prevention and treatment of atherosclerotic
cardiovascular disease.