Differential roles (OX1R for feeding/motivation, OX2R for arousal/thermogenesis) enable precision: OX1R agonists for hypoglycemia, DORAs for chrono-disrupted T2DM, and positioning orexin modulation as versatile for personalized metabolic therapy (Tsuneki et al., 2016; Kaczmarek et al., 2017). This evidence concerns the gene HCRTR1 and Hypoglycemia.