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These interventions, recognized for their ability to modulate oxidative stress and suppress pro-inflammatory cytokines, offer pain relief and functional enhancement in patients with knee OA [3, 43, 44]

Rambold AS, Lippincott-Schwartz J

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Recent data suggest that not only hyperinsulinemia but also excess liver fat are among the main inhibitory influences on SHBG secretion in obese subjects, in a process in which pro-inflammatory cytokines derived from ectopic adipose tissue are likely implicated (213)

It effectively "jump starts" the idling neurons identified on PET/qEEG [8]

Furthermore, the gastrointestinal tract also has a major role in metformin action through modulation of glucose-lowering hormone glucagon-like peptide 1 and the intestinal bile acid pool and alterations in gut microbiota composition