This dual regulatory profile mobilization in deficit and sensitivity in excess positions orexin as a high-value therapeutic target: OX1R/OX2R agonists could counter hypoglycemia unawareness in diabetes, while dual orexin receptor antagonists (DORAs) like suvorexant may improve insulin sensitivity in type 2 diabetes, particularly when timed to circadian rhythms. Here, HCRT is linked to type 2 diabetes mellitus.