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#Diabetes and Endocrinology
Metformin, the first-line drug for the treatment of type 2 diabetes mellitus, has been found to be associated with fewer adverse cardiovascular events and a reduced risk of cancer in some studies. Therefore, the researchers attempted to evaluate its anti-inflammatory effects and their link to antihyperglycemic properties. They showed that metformin inhibited tumor necrosis factor-alpha–dependent IκB degradation and expression of proinflammatory mediators, interleukin-6, interleukin-1beta, and C-X-C motif ligand 1/2 in primary hepatocytes of experimental models. It suppressed activation of inhibitor of kappa B kinase (IKK) alpha/beta, an effect that could be separated from few metabolic actions. This drug decreased proinflammatory cytokines’ secretion in macrophages without blocking differentiation or activation of M1/M2.
Furthermore, on investigating the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) patient database, it was found that metformin reduced subclinical inflammation, as measured by neutrophil to lymphocyte ratio in patients. The researchers observed differences in the systemic inflammation marker, neutrophil to lymphocyte ratio, after incident treatment with either metformin or sulfonylurea monotherapy in the treatment naive diabetes mellitus population cohort. It was seen that in comparison to sulfonylurea, metformin reduced the mean log-transformed neutrophil to lymphocyte ratio after 8-16 months by 0.09 U and increased the probability of lower neutrophil to lymphocyte ratio than baseline after 8-16 months.
Previous reports have also shown that this agent has the ability to suppress inflammatory markers such as high-sensitivity C-reactive protein in prediabetic individuals and tumor necrosis factor-alpha in individuals who are insulin resistant. As neutrophil to lymphocyte ratio is considered a predictor of cardiovascular events and all-cause mortality, studies conducted in the past have shown a positive impact of metformin therapy on cardiovascular outcomes. In another double-blind placebo-controlled trial involving patients with non-diabetic heart failure, metformin suppressed plasma cytokines, including the aging-associated cytokine C-C motif chemokine ligand 11. Therefore, it can be concluded that metformin exhibits anti-inflammatory actions, beyond its glucose lowering effects.
- Cameron AR, Morrison VL, Levin D, et al. Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status. Circ Res. 2016;119(5):652-665.