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Neprilysin inhibition: a new therapeutic option for type 2 diabetes? – published online 14/05/2019

Figure from Esser paper

Nathalie Esser, Sakeneh Zraika

Neprilysin is a peptidase that hydrolyses oligopeptide substrates, such as glucagon-like peptide-1, which are known to regulate glucose homeostasis. Recent studies in humans with diabetes have demonstrated that a new class of drug for heart failure, which combines a neprilysin inhibitor with an angiotensin receptor blocker, improves glycaemic control, enhances insulin sensitivity and reduces the need for initiation of insulin therapy. In this issue, Esser and Zraika (https://doi.org/10.1007/s00125-019-4889-y) summarise these data, with an emphasis on neprilysin inhibition as the principal contributor to these positive clinical outcomes. The authors also review supporting data from preclinical studies to make the case that neprilysin inhibition may be a novel therapeutic approach for the treatment of type 2 diabetes. Potential mechanisms underlying beneficial glycaemic effects are discussed, as well as possible deleterious effects that may limit the clinical use of neprilysin inhibitors. Beyond its beneficial impact on glycaemic control, neprilysin inhibition could also exert favourable effects in treating complications of diabetes. The figures from this review are available as a downloadable slideset.

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