INCB-13739, an 11beta-hydroxysteroid dehydrogenase type 1 inhibitor for the treatment of type 2 diabetes.

Abstract

INCB-13739, being developed by Incyte Corp, is a novel, first-in-class 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitor for the potential treatment of metabolic disorders, including type 2 diabetes mellitus (T2DM) and obesity. INCB-13739 has high selectivity for 11beta-HSD1 over other dehydrogenases and glucocorticoid and mineralocorticoid receptors, with prolonged pharmacodynamic activity and good pharmacokinetic/pharmacodynamic properties. INCB-13739 demonstrated improved hepatic and peripheral insulin sensitivity with a satisfactory reduction in fasting plasma glucose and cholesterol after 28 days of treatment in patients with T2DM, with a dose-dependent weight loss, decrease in triglyceride levels and an improvement in blood pressure. Clinical data demonstrated that INCB-13739 had a better efficacy to tolerability ratio compared with potential competitors. The unique differentiation of INCB-13739 is its effects on both glucose and lipid parameters coupled with its effects on body weight and hypertension. The results from phase III clinical trials will be pivotal; however, the available data suggest that INCB-13739 has potential for success in the market.