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Metformin treatment is associated with the increased presence of Akkermansia muciniphila in the gut lumen, which promotes the maintenance of intestinal barrier integrity, the increment of short-chain fatty acids with positive actions on peripheral tissues (adipose tissue, skeletal muscle, and liver) by improving insulin sensitivity [49,51,52], and reduced reabsorption of bile acids in the distal ileum, resulting in increasing bile salt levels within the colon, which might modify its microbiota [53,54] (Figure 1)

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(Supplemental Table 2) Study selection and data collection Selected titles and abstracts were then imported into the Covidence systemic review software package (Veritas Health Innovation, Melbourne, Australia)