Metformin increases glycolysis and the stress-induced cytokine GDF15 but not FGF21 in humans
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By
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March 18, 2026
Objective:
To examine the effect of metformin on GDF15 and FGF21 levels in humans and in intestinal cells in vitro.
Key Findings:
- Metformin increased glucose utilization and glycolysis in vivo (p=8.9x10-13; p=7.6x10-13).
- Serum GDF15 levels significantly increased with metformin treatment (1004±61 vs 607±89 ng/ml; p<0.001).
- Serum FGF21 levels remained unchanged (146±30 vs 156±29 ng/ml; p=0.65).
- In vitro, metformin increased GDF15 mRNA levels and secretion, while FGF21 was not detectable.
Interpretation:
The increase in serum GDF15, but not FGF21, suggests that the gastrointestinal tract is a key site of metformin's action in humans, highlighting its potential role in metabolic regulation.
Limitations:
- The study involved a small sample size of healthy individuals, limiting generalizability.
- The effects of metformin on GDF15 and FGF21 were not correlated with plasma metformin levels, indicating other factors may influence these outcomes.
Conclusion:
Metformin enhances GDF15 levels without affecting FGF21, supporting the role of the gastrointestinal tract in its mechanism of action.
