In this study we examine the role of combination therapy with SPTC + exercise and SPTC + metformin compared with each treatment alone to improve T2DM complication and stress oxidative markers include antioxidant capacity and Nrf2-keap1 signaling pathways in AGE rich diet-induced type 2 diabetic mice. The gene discussed is NFE2L2; the disease is type 2 diabetes mellitus.