INS and obesity due to melanocortin 4 receptor deficiency: For instance, Al-Jarallah et al observed that insulin therapy in DM patients was linked to diminished radiographic osteophyte formation in knee OA, suggesting insulin’s potential protective role against OA progression in this demographic.[20] Similarly, Nieves-Plaza et al found that, even after adjusting for variables like age, obesity, depression, and cardiovascular complications, the lack of insulin use was significantly correlated with a heightened risk of hand or knee OA.