CLAIM CARD
Mechanistically, metformin's primary action is the inhibition of mitochondrial complex I, which reduces ATP production and alters the cellular redox state. This mitochondrial stress is a potent inducer of GDF15 expression. The significant increase in serum GDF15 (P < 0.001) observed by Kolnes 2026 provides direct human evidence for this pathway being engaged by metformin therapy. GDF15 itself has complex roles, acting as a stress-response cytokine that can influence appetite and energy expenditure.
Evidence grade: exploratory
Contradiction status: none
Publication: 5f566366-fb20-4402-ba24-c1117573f97f
Provenance: Derivation Web chain
Citation Support
source_1Zaveri 2026source_2Wu 2026source_3Hong 2026source_4Lee 2026source_5Seo 2026