TABLE 2.

Possible mechanisms of beneficial effects of NEP inhibitors.

Study type	Findings	Ref.
Experimental study	NEP inhibitors increase GLP‐1 level.	Hupe‐Sodmann et al 54
Experimental study	NEP inhibitors insulin sensitivity by increasing of GLP‐1 and decrease DPP4 activity.	Willard et al 36
Experimental study	Dual inhibition of DPP4 and NEP increases the half‐life of GLP‐1.	Plamboeck et al 40
A randomized, controlled study	Augmentation of GIP by NEP inhibitors improves glucose homeostasis and insulin sensitivity in T2DM patients.	Frias et al 56
Review	NEP inhibitors improve glucose homeostasis and insulin sensitivity by increasing level of NPs.	Moro et al 60
Review	NEP inhibitors improve insulin sensitivity and glucose homeostasis by increasing bradykinin level.	Campbell 64
Review	LCZ696 can enhance insulin sensitivity and glucose homeostasis by increasing oxytocin serum level.	Dargad et al 68

Abbreviations: DPP4, dipeptidyl peptidase‐4; GIP, glucose‐dependent insulinotropic peptide; GLP‐1, glucagon‐like peptide 1; NEP, neprilysin; NP, natriuretic peptide; T2DM, type 2 diabetes mellitus.