Azelnidipine and glucose tolerance: possible indications and treatment selection for hypertensive patients with metabolic disorders

Abstract

Azelnidipine is a unique dihydropyridine calcium channel blocker with selectivity for L-type calcium channels that has been launched for the treatment of hypertension. Azelnidipine exhibits long-acting blood pressure-lowering effects without increasing heart rate. High blood pressure is associated with many metabolic disorders, including glucose intolerance and insulin resistance. Antihypertensive medications that interfere with various steps in the renin–angiotensin system improve glucose tolerance and insulin resistance; however, the effects of calcium channel blockers on glucose metabolism and insulin resistance remain controversial. Recent studies have demonstrated that azelnidipine could improve insulin resistance and glucose tolerance by potentially inhibiting sympathetic nerve activity. In addition, azelnidipine exhibits anti-inflammatory and anti-oxidative effects, suggesting that it is a beneficial antihypertensive agent with anti-atherogenic and cardioprotective effects for the treatment of not only hypertensive patients with glucose intolerance, but also those with metabolic disorders.

Keywords:

• anti-atherogenic effect
• anti-inflammatory effect
• anti-oxidative effect
• azelnidipine
• cardiovascular and metabolic disorders
• essential hypertension
• glucose tolerance
• insulin resistance

Financial & competing interests disclosure

The authors were supported by a High Technology Research Center Grant from the Ministry of Education, Culture, Science and Technology of Japan and a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science, Japan (C-26350588). K Shimada and K Miyauchi received lecture fees from Daiichi Sankyo Co., Ltd. (Tokyo, Japan). H Daida received scholarship funds and lecture fees from Daiichi Sankyo Co., Ltd. (Tokyo, Japan). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Elevated blood pressure is associated with an increased risk of cardiovascular morbidity and mortality.

• The incidence of cardiovascular disease and metabolic diseases continue to increase worldwide.

• Hypertension is associated with metabolic disorders, including glucose intolerance, insulin resistance and an increased risk for new-onset DM.

• The co-existence of hypertension and DM increases the risk of cardiovascular disease increases by two- to threefold.

• Medical treatment to prevent new onset of DM and control blood pressure is important even in non-DM patients with hypertension.

• Azelnidipine, which is a dihydropyridine calcium channel blocker with selectivity for L-type calcium channels, exhibits long-acting blood pressure-lowering effects without increasing heart rate.

• Azelnidipine treatment has beneficial effects on glucose tolerance, insulin sensitivity, oxidative stress and inflammatory state in patients with essential hypertension and/or glucose intolerance.

• Azelnidipine treatment may increase the number of circulating progenitor cells in non-DM patients with essential hypertension.

Notes