MIF/CD74 axis is a target for metformin therapy in diabetic podocytopathy - real world evidence

Introduction: To observe the effects of metformin on urinary excretion of MIF, CD74, and podocalyxin in type 2 diabetics, and to explore its possible renoprotective mechanisms. Material and methods: A total of 202 uncontrolled type 2 diabetics, who were previously prescribed sulfonylurea monotherapy (n = 100) or sulfonylurea in combination with metformin (n = 102), were enrolled in the study. The amount of macrophage migration inhibitory factor (MIF) and CD74 in serum, urinary MIF-to-creatine ratio (UMCR), urinary CD74-to-creatine ratio (UCCR), urinary albumin-tocreatine ratio (UACR), and urinary podocalyxin-to-creatine ratio (UPCR) were determined. Results: Metabolic parameters including fasting blood glucose, postprandial two hours blood glucose, haemoglobin A1c, MIF, and CD74 in serum were comparable between the two groups. Moreover, metformin add-on therapy showed significantly better efficacy in reducing UMCR, UCCR, UPCR, and UACR in comparison with those in the sulfonylurea monotherapy group, respectively. UPCR had a positive correlation with UACR, UMCR, and UCCR (r = 0.73, r = 0.69, r = 0.62, P < 0.01), respectively. Conclusions: Metformin could present its podocyte-protective capacity in type 2 diabetics, and the underlying mechanisms may be partly attributed to its effects in suppressing MIF-CD74 axis-mediated inflammatory cascade response.