Neprilysin inhibitors: A new hope to halt the diabetic cardiovascular and renal complications?

Abstract

Diabetes is an enormous and ever-growing calamity and a global public health threat of the 21st century. Besides insulin and oral hypoglycaemic drugs, blockage of the renin-angiotensin system (RAS) denotes a key pharmacotherapy for the management of cardiovascular (CVD) and chronic kidney diseases (CKD), which are the leading causes of disability and death among diabetic patients. Neprilysin (NEP) inhibition, auxiliary to RAS blockage increases the bioavailability of natriuretic peptides and benefits the cardio-renal system. Omapatrilat, a dual angiotensin-converting enzyme (ACE) and NEP inhibitor has been reported to show superior anti-hypertensive, anti-atherosclerotic, insulin-sensitizing, cardiovascular and renoprotective effects to ACE inhibitors in experimental animal models for diabetes. In clinical trials on hypertensive subjects Omapatrilat increased the risk of angioedema due to which its further development as anti-hypertensive drug was hampered. This event prompted the development of angiotensin receptor neprilysin inhibitors (ARNi). The first representative of ARNi, LCZ696 (Sacubitril/ Valsartan) halted cardiovascular and renal functional decline and hence protected against CKD and CVD. Recently, LCZ696 was approved by U.S. Food and Drug Administration for the treatment of heart failure. This concise review intends to summarise the currently available reports on NEPi as a therapeutic intervention to treat CVD and CKD associated with diabetes.

• Authors: Vajir Malek, Anil Bhanudas Gaikwad
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 90 Pg. 752-759 (Jun 2017) ISSN: 1950-6007 [Electronic] France
• PMID: 28419972 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Chemical References

• Aminobutyrates
• Antihypertensive Agents
• Biphenyl Compounds
• Drug Combinations
• Tetrazoles
• Valsartan
• Neprilysin
• sacubitril and valsartan sodium hydrate drug combination

Topics

• Aminobutyrates (pharmacology, therapeutic use)
• Animals
• Antihypertensive Agents (pharmacology, therapeutic use)
• Biphenyl Compounds
• Cardiovascular Diseases (drug therapy, etiology)
• Diabetes Complications (drug therapy)
• Diabetes Mellitus
• Drug Combinations
• Humans
• Neprilysin (antagonists & inhibitors)
• Renal Insufficiency, Chronic (drug therapy, etiology)
• Tetrazoles (pharmacology, therapeutic use)
• Valsartan