Metformin has become the frontline treatment in addressing the significant global health challenge of type 2 diabetes due to its proven effectiveness in lowering blood glucose levels. However, the reality is that many patients struggle to achieve their glycemic targets with the medication and the cause behind this variability has not been investigated thoroughly. While genetic factors account for only about a third of this response variability, the potential influence of metabolomics and the gut microbiome on drug efficacy opens new avenues for investigation. This review explores the different molecular signatures to uncover how the complex interplay between genetics, metabolic profiles, and gut microbiota can shape individual responses to metformin. By highlighting the insights from recent studies and identifying knowledge gaps regarding metformin-microbiota interplay, we aim to highlight the path toward more personalized and effective diabetes management strategies and moving beyond the one-size-fits-all approach.
Keywords: genomics; metabolomics; metformin; microbiomics; precision medicine.
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