Since the NF-κB pathway is engaged in proinflammatory cytokine expression, metformin treatment reduces the expression of TNF and CRP in T2DM patients Additionally, in the intestine, a supra-pharmacological concentration of metformin inhibited the differentiation of monocytes into macrophages via AMPK induction, triggering a decrease in proinflammatory cytokine secretion, as well as activating macrophage polarization into functional M2 phenotypes characterized by anti-inflammatory properties [147]. The gene discussed is PRKAA1; the disease is type 2 diabetes mellitus.