INS and obesity due to melanocortin 4 receptor deficiency: These findings indicate that by restoring PI3K/Akt signaling, enhancing GLUT4 translocation, increasing microvascular recruitment, reducing intramuscular lipid accumulation and lipotoxic signaling, GLP-1 RAs can enhance skeletal muscle glucose uptake and improve metabolic flexibility in patients with an insulin-resistant state, such as obesity and T2D.