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Metformin, the current first-line treatment in T2DM, has an unclear antidepressant effect [166] despite identified direct mechanisms and pleiotropic effects, including inhibition of angiotensin II and NF-B factor, normalization of gut microbiota, and intestinal permeabilization, and in vivo experimental data [167] supporting its potential benefits

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These effects are consistent with lower thrombo-inflammation, slower progression toward myelofibrosis and decreased leukemic transformation risk