Abstract
Antihypertensive drugs that inhibit the renin–angiotensin system (RAS) have been proposed to have additional benefits beyond their classic effects on the cardiovascular system, including reducing the risk of new-onset diabetes. Whether RAS inhibitors vary in ability to protect against new-onset diabetes is, however, unknown. The angiotensin II type 1 receptor (AT1) blocker telmisartan has been discovered to also activate the peroxisome proliferator-activated receptor-γ (PPARγ), an established antidiabetic drug target. In patients with hypertension and biochemical features of the metabolic syndrome, telmisartan has had beneficial effects on lipid and glucose metabolism. As a selective modulator of PPARγ, telmisartan does not cause the side effects of fluid retention and weight gain associated with conventional thiazolidinedione ligands of PPARγ. These observations raise the possibility that combined AT1 receptor blockade and selective PPARγ modulation with molecules such as telmisartan could provide greater protection from new-onset diabetes and cardiovascular disease than drugs that target either the RAS or PPARγ alone. The cardioprotective and antidiabetic effects of telmisartan are being assessed in two large clinical trials, the ONgoing Telmisartan Alone in combination with Ramipril Global Endpoint Trial (ONTARGET) and the Telmisartan Randomised AssessmeNt Study in ACE-I iNtolerant subjects with cardiovascular Disease (TRANSCEND).
Key Points
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Patients with hypertension and the metabolic syndrome are at greatly increased risk of developing new-onset diabetes, and for this reason blood-pressure-lowering drugs with antidiabetic properties could be of considerable clinical value
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Antihypertensive drugs that inhibit the renin–angiotensin system might have some beneficial effects on glucose metabolism, but the antidiabetic properties of these drugs are modest compared with those of drugs that activate the peroxisome proliferator-activated receptor-γ
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The commonly used antihypertensive agent telmisartan can activate peroxisome proliferator-activated receptor-γ as well as block the angiotensin II type 1 receptor and could, therefore, provide greater metabolic and cardiovascular protection than drugs that inhibit the renin–angiotensin system alone
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Ongoing clinical trials are being done to compare the effects of telmisartan, the angiotensin-converting-enzyme inhibitor ramipril, and combined telmisartan and ramipril on the rates of cardiovascular events and new-onset diabetes in high-risk populations
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PAREXEL MMS provided writing assistance, comprising preparation of a draft from slides and audio transcript, preparation of figures and obtaining copyright permissions, proofreading, and reference checking.
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TW Kurtz has received lecture honoraria from Boehringer Ingelheim, GlaxoSmithKline, Pfizer and Merck. He has also declared associations with companies that sell or have financial interests in angiotensin II receptor antagonists and ligands for proliferator-activated receptor-γ.
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Kurtz, T. Beyond the classic angiotensin-receptor-blocker profile. Nat Rev Cardiol 5 (Suppl 1), S19–S26 (2008). https://doi.org/10.1038/ncpcardio0805
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DOI: https://doi.org/10.1038/ncpcardio0805
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