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9,14 Metformin clearance depends on renal function and declines in the presence of renal impairment

This fundamentally changed the way we think about this class

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This dual action is a key distinction

Emerging evidence suggests that treatment with the dual GLP-1 and GIP receptor agonist, tirzepatide, might prove even more potent than a GLP-1RA alone, to ameliorate NAFLD

Mechanistic sampling of intestinal tissue during this trial would best validate the reparative hypothesis if analyses include tight junction protein expression (e.g., claudins, occludin, zonula occludens-1), histologic healing assessments using validated indices (e.g., Geboes score, Robarts Histopathology Index), and intestinal permeability assays such as the lactulose-mannitol ratio