The study showed that DNJ-TFs alleviate high-fat-induced inflammation and IR by targeting PTGS2 or MMP9 via the TNFα/AKT/GSK3/GLUT2 signaling pathway, and the synergistic anti-glycemic effect of the two drugs has a synergistic hypoglycemic effect, which provides new clues for the prevention and treatment of high-fat-induced T2DM and a new idea for the development of glucose-lowering products. Here, MMP9 is linked to type 2 diabetes mellitus.