Microbial aldehyde-alcohol dehydrogenase degrades metformin to limit therapeutic response in type 2 diabetes.

Gut microbial enzyme AdhE degrades metformin, reducing its effectiveness in treating type 2 diabetes, especially in low-responders, by lowering systemic drug levels.

• Why it matters: Understanding microbial inactivation of metformin addresses a key reason for the variability in patient responses and offers potential to enhance therapeutic outcomes.
• What they did: Researchers identified AdhE from Eubacterium species that converts metformin into inactive products, and used genetic and phage methods to restore drug exposure in mice, also screening for inhibitors.
• The result: Inhibiting AdhE with dietary compound daidzein improved metformin efficacy, suggesting microbial enzyme targeting as a strategy to optimize diabetes treatment.