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Type 2 diabetes mellitus (T2DM) is a complex chronic disease characterized by progressive β-cell dysfunction and insulin resistance. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used in T2DM management due to their ability to lower HbA1c, promote weight loss, and offer cardiovascular and renal protection. However, inter-individual variation in therapeutic response has been observed, potentially influenced by gut microbiota composition. A brief review was conducted to explore current evidence on the interaction between GLP-1RAs and gut microbiotatermed the "pharmaco-gut axis." Literature was examined to understand how specific microbial populations affect drug efficacy and insulin sensitivity. Studies suggest that certain gut microbes, including Bacteroides species, Akkermansia muciniphila, and those producing short-chain fatty acids (SCFAs), enhance GLP-1RA efficacy by improving insulin sensitivity and stimulating endogenous GLP-1 secretion. Conversely, dysbiosis characterized by reduced microbial diversity and increased lipopolysaccharide (LPS)-producing pro-inflammatory bacteria correlates with poor therapeutic response. Furthermore, GLP-1RAs may exert beneficial modulatory effects on the gut microbiota itself, indicating a bidirectional relationship. The interaction between GLP-1RAs and gut microbiota introduces a novel pharmaco-gut interface, emphasizing the role of microbial composition in drug response. This emerging concept has the potential to enhance precision medicine in diabetes care by utilizing microbiome profiling to guide GLP-1RA therapy and improve clinical outcomes.