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Additionally, not everyone benefits equally from metformin therapy, some experience negative effects as well ( Investigations conducted in animal models validated that metformin-induced modulation of gut microbiome resulted in the formation of short-chain fatty acids (SCFAs), reduced lipopolysaccharides in circulation, impeded intestinal proinflammatory signalling and altered hepatic uptake of metformin (Zhang et al., 2019

33,34 DKD is driven by a cascade of hemodynamic disturbances, dysregulated metabolism, and inflammatory and fibrotic processes, along with epigenetic changes (Fig