Metformin, a common treatment for type 2 diabetes (T2D), increases levels of the appetite-suppressing metabolite N-lactoyl phenylalanine (Lac-Phe) in humans. A study involving 33 volunteers from Brigham and Women's Hospital found significantly higher Lac-Phe levels in obese T2D individuals compared to non-T2D controls. Lac-Phe levels also rose in response to metformin and post-meal in both T2D and metabolically healthy volunteers. The study confirmed that metformin treatment is linked to increased Lac-Phe levels, with a strong correlation between metformin and Lac-Phe concentrations in T2D individuals. Further analysis of the TwinsUK cohort showed that Lac-Phe levels increased in T2D individuals who started metformin treatment, and that metformin was the most significant factor influencing Lac-Phe levels. Interventional studies also showed that metformin treatment led to increased Lac-Phe levels, with a significant rise observed after a 12-week intervention. Additionally, acute metformin treatment resulted in increased Lac-Phe levels, as shown in a study with 26 healthy men. The study also found that Lac-Phe levels increased after meals, suggesting a role in appetite regulation. The findings indicate that metformin increases Lac-Phe levels, which may contribute to its appetite-suppressing effects. The study also found that metformin increases levels of at least five N-lactoyl amino acids, broadening understanding of metformin's metabolic effects. The study highlights the potential of targeting Lac-Phe pharmacologically to develop new treatments for obesity. The research was supported by the National Institutes of Health and Science Foundation Ireland. The authors declare no competing interests.Metformin, a common treatment for type 2 diabetes (T2D), increases levels of the appetite-suppressing metabolite N-lactoyl phenylalanine (Lac-Phe) in humans. A study involving 33 volunteers from Brigham and Women's Hospital found significantly higher Lac-Phe levels in obese T2D individuals compared to non-T2D controls. Lac-Phe levels also rose in response to metformin and post-meal in both T2D and metabolically healthy volunteers. The study confirmed that metformin treatment is linked to increased Lac-Phe levels, with a strong correlation between metformin and Lac-Phe concentrations in T2D individuals. Further analysis of the TwinsUK cohort showed that Lac-Phe levels increased in T2D individuals who started metformin treatment, and that metformin was the most significant factor influencing Lac-Phe levels. Interventional studies also showed that metformin treatment led to increased Lac-Phe levels, with a significant rise observed after a 12-week intervention. Additionally, acute metformin treatment resulted in increased Lac-Phe levels, as shown in a study with 26 healthy men. The study also found that Lac-Phe levels increased after meals, suggesting a role in appetite regulation. The findings indicate that metformin increases Lac-Phe levels, which may contribute to its appetite-suppressing effects. The study also found that metformin increases levels of at least five N-lactoyl amino acids, broadening understanding of metformin's metabolic effects. The study highlights the potential of targeting Lac-Phe pharmacologically to develop new treatments for obesity. The research was supported by the National Institutes of Health and Science Foundation Ireland. The authors declare no competing interests.