Figure 4.

Future directions of studying the pharmacological actions and molecular mechanisms of metformin in atherosclerosis. Numerous studies have demonstrated the protective effects of metformin on macrophage function, however, the effect of metformin on atherosclerosis in experimental animal models and humans are warranted. Recent studies have shown that neutrophils (the most abundant white blood cells in healthy people) can participate in the development of AS through the formation of NETs. Moreover, single-cell RNA sequencing plays an increasingly important role in revealing various physiological and pathological mechanisms, and can be further utilized to uncover the effects of metformin on monocytes/macrophages and neutrophils. This will provide important clues for the study of immune memory and the exploration of new treatment methods. In addition, the combination of metformin and other drugs (such as statins and SGLT2i) synergistically improves the function of macrophages, further enhancing the pleiotropic effects of metformin. NETs, neutrophil extracellular traps; SGLT2i, sodium-glucose cotransporter 2 inhibitors.