Metformin-regulated glucose flux from the circulation to the intestinal lumen.

Summary

Using continuous FDG PET/MRI, the study shows that a substantial glucose flux from blood to the intestinal lumen exists and begins in the jejunum, and that metformin treatment markedly increases this excretion in people with type 2 diabetes. Mouse fecal metabolomics indicate that excreted glucose is metabolized by gut microbiota, suggesting a mechanistic link between metformin, intestinal glucose handling, and host–microbiome symbiosis.

Key Findings

• Continuous FDG PET/MRI revealed initial appearance of FDG in the jejunum, indicating jejunal involvement in intestinal glucose excretion.
• Metformin-treated individuals excreted a substantially higher amount of glucose into the intestinal lumen (on the order of grams per hour).
• Mouse fecal mass spectrometry showed that excreted glucose is metabolized by gut microbiota.
• Findings support a significant circulation-to-lumen glucose flux as a potential target of metformin’s action.

Clinical Implications

Mechanistic insights may explain metformin’s gastrointestinal effects and microbiome-mediated benefits, informing optimization of dosing, formulation, and potential combination therapies targeting the gut–microbiome axis.

Limitations

• Sample size and participant characteristics are not detailed in the abstract; generalizability requires confirmation.
• Observational comparison of metformin-treated vs untreated limits causal inference; long-term clinical impacts were not assessed.

Future Directions

Quantify variability and determinants of intestinal glucose excretion, assess effects of metformin dose/formulation, and test whether modulating this flux alters glycemic control, microbiome composition, and cardiometabolic outcomes.