PP18

PP18 is a novel oxyntomodulin (OXM)-based derivative, specifically a hybrid OXM derivative (3-37) that was further site-specifically modified with fatty acid chains. It functions as a dual agonist for both glucagon-like peptide-1 (GLP-1) and glucagon receptors. Preclinical studies have shown that PP18 retains the balanced activation potency of its precursor (PP11) in these receptors, while also demonstrating enhanced plasma stability and prolonged hypoglycemic activity. It acts as an insulin secretagogue and glycemic agent, and has shown protracted antidiabetic effects and an extended in vivo half-life. In diet-induced obesity (DIO) mice, daily administration of PP18 normalized food intake, body weight, blood biochemical indexes, insulin resistance, and islet function. These findings suggest its potential as a therapeutic approach for type 2 diabetes mellitus and obesity.