AUTHOR=Naja Khaled , Anwardeen Najeha , Malki Ahmed M. , Elrayess Mohamed A. TITLE=Metformin increases 3-hydroxy medium chain fatty acids in patients with type 2 diabetes: a cross-sectional pharmacometabolomic study JOURNAL=Frontiers in Endocrinology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1313597 DOI=10.3389/fendo.2024.1313597 ISSN=1664-2392 ABSTRACT=Background

Metformin is a drug with a long history of providing benefits in diabetes management and beyond. The mechanisms of action of metformin are complex, and continue to be actively debated and investigated. The aim of this study is to identify metabolic signatures associated with metformin treatment, which may explain the pleiotropic mechanisms by which metformin works, and could lead to an improved treatment and expanded use.

Methods

This is a cross-sectional study, in which clinical and metabolomic data for 146 patients with type 2 diabetes were retrieved from Qatar Biobank. Patients were categorized into: Metformin-treated, treatment naïve, and non-metformin treated. Orthogonal partial least square discriminate analysis and linear models were used to analyze differences in the level of metabolites between the metformin treated group with each of the other two groups.

Results

Patients on metformin therapy showed, among other metabolites, a significant increase in 3-hydroxyoctanoate and 3-hydroxydecanoate, which may have substantial effects on metabolism.

Conclusions

This is the first study to report an association between 3-hydroxy medium chain fatty acids with metformin therapy in patients with type 2 diabetes. This opens up new directions towards repurposing metformin by comprehensively understanding the role of these metabolites.