Metformin increases glycolysis and the stress-induced cytokine GDF15 but not FGF21 in humans

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  • 1

    Metformin significantly increases glucose utilization and glycolysis in healthy individuals during fasting.

  • 2

    Serum GDF15 levels rise significantly with metformin treatment, while FGF21 levels remain unchanged.

  • 3

    The increase in GDF15 does not correlate with plasma metformin levels, indicating a distinct regulatory mechanism.

  • 4

    In vitro studies show metformin enhances GDF15 expression and secretion in intestinal cells, but FGF21 is undetectable.

  • 5

    These findings suggest the gastrointestinal tract plays a crucial role in metformin's action, particularly in GDF15 release.

Original Source(s)

Metformin increases glycolysis and the stress-induced cytokine GDF15 but not FGF21 in humans

  • by Kristoffer J. Kolnes, Pauline M. Møller, Rikke Kruse, Mette Marie H. Christensen, Rasmus Kjøbsted, Martin Hey-Mogensen, Birgitte Andersen, Aase Handberg, Kurt Højlund

  • March 18, 2026

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