Pharmacomicrobiomics: Exploring the role of gut microbiota in type 2 diabetes and antidiabetic drug mechanisms

Oct 28, 2025Nutrition, metabolism, and cardiovascular diseases : NMCD

How Gut Bacteria May Influence Type 2 Diabetes and How Diabetes Medicines Work

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Abstract

Antidiabetic drugs significantly alter gut microbial composition and functionality.

Various drug classes, including metformin and SGLT2 inhibitors, are associated with changes in the gut microbiome, such as shifts in the Bacteroidetes to Firmicutes ratio.
Alterations in gut microbial composition may contribute to improved glycemic control and cardiorenal benefits of these drugs.
The gut microbiota may also influence the metabolism of antidiabetic medications and is linked to common side effects, including gastrointestinal issues.
Understanding the interaction between gut microbiota and antidiabetic drugs may help personalize treatment strategies for type 2 diabetes mellitus.

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BACKGROUND AND AIM: The gut microbiota is intricately linked to the pathogenesis of type 2 diabetes mellitus (T2DM). This review aims to explore the bidirectional interaction between antidiabetic drugs and the gut microbiota, focusing on how drugs modulate the microbiome to exert therapeutic effects and how this interaction influences common drug side effects, thereby outlining the role of pharmacomicrobiomics in personalizing T2DM treatment.

METHODS AND RESULTS: We comprehensively reviewed literature from PubMed, Scopus, and Embase on gut microbiota, T2DM, and antidiabetic drugs. Evidence indicates that various drug classes (e.g., metformin, sodium glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists (RAs), α-glucosidase inhibitors (AGIs)) significantly alter gut microbial composition (e.g., Bacteroidetes - to -Firmicutes ratio), functionality, and metabolite production (e.g., SCFAs, bile acids). These changes contribute not only to glycemic control but also to the drugs' cardiorenal benefits. Conversely, the microbiota influences drug metabolism and is implicated in the manifestation of typical side effects, such as gastrointestinal disturbances from metformin and acarbose.

CONCLUSIONS: The gut microbiota is a crucial mediator of both the efficacy and toxicity of antidiabetic drugs. Understanding pharmacomicrobiomics provides a novel framework for developing personalized therapeutic strategies in T2DM, potentially using an individual's microbiome as a biomarker for drug selection and side effect prediction.

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Pharmacomicrobiomics: Exploring the role of gut microbiota in type 2 diabetes and antidiabetic drug mechanisms

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