Summary: In a crossover trial in prediabetes, pairing metformin with a moderate-FODMAP (fermentable-carbohydrate) diet lowered postprandial glucose and raised GLP-1 secretion compared with a low-FODMAP diet plus metformin, alongside gut microbiota shifts, with a baseline microbe predicting metformin intolerance.
PICO Summary
| Element | Detail |
|---|---|
| Population | 26 individuals with prediabetes; double-blind randomised crossover, Hong Kong. |
| Intervention | Isocaloric moderate-FODMAP diet for 10 days plus metformin for 5 days. |
| Comparison | Isocaloric low-FODMAP diet plus metformin (2-week washout between periods). |
| Outcome | Moderate-FODMAP plus metformin gave lower postprandial glycaemia (CGM incremental AUC), higher GLP-1 secretion, and higher Butyricimonas virosa abundance. Higher baseline Dorea formicigenerans predicted gastrointestinal intolerance to metformin. |
Expert Commentary
This is a clever, mechanistically rich study that reframes diet not as an alternative to metformin but as a way to enhance it. The biology hangs together: fermentable carbohydrates feed gut bacteria that produce short-chain fatty acids and stimulate GLP-1, so combining a higher-FODMAP diet with metformin plausibly amplifies the incretin response and improves postprandial glucose, which is what was seen. The microbiome signals, enrichment of butyrate-related organisms and a baseline microbe that flags who will tolerate metformin poorly, point intriguingly toward personalising both diet and drug. I would keep expectations measured. This is a small, short, crossover proof-of-concept using surrogate glucose endpoints rather than HbA1c or diabetes prevention, the comparison was moderate versus low FODMAP rather than diet versus none, and higher-FODMAP eating can itself cause bloating and discomfort, so tolerability cuts both ways. Can I use this with my patients? Cautiously and directionally. It supports encouraging fermentable plant fibre alongside metformin in prediabetes, and hints at a future where a stool profile guides who gets which approach, while I await larger trials with hard glycaemic endpoints before making it a formal recommendation.
References
Chu NHS, Ling J, Poon EWM, et al. Combining a diet rich in fermentable carbohydrates with metformin improves glycaemic control and reshapes the gut microbiota in people with prediabetes. Nat Metab. 2025;7(8):1614–1629. doi:10.1038/s42255-025-01336-4