INS and Hyperglycemia: On the other hand, effects of glucagon-like peptide-1 (GLP-1) signaling are responsible for stimulation of insulin release in the pancreatic β-cells, thus alleviating hyperglycemia, while the inhibition of neprilysin with agents such as sacubitril is implicated in the augmentation of GLP-1 signaling which might have a clinical relevance in patients with HF, both with or without diabetes (Packer, 2018b).