Can individual gastrointestinal microbiome composition and diversity predict individual clinical response to anti-diabetic medication in human adults? A systematic review and narrative synthesis

Background Type 2 diabetes is a major worldwide barrier to healthcare and has a variable response to common anti-diabetic medication. Evidence suggests this variability may be related to the relationship between these medications and the intestinal microbiome. There are multiple different noted mechanisms by which the baseline gut microbiota can modulate anti-diabetic medication, particularly certain Bacteroides and Klebsiella species affecting metformin and acarbose action respectively. Objective This review aims to synthesize the available evidence on whether baseline gut microbiota composition can predict ADM efficacy in adult populations with type 2 diabetes mellitus. Methods A comprehensive search was performed across the major databases Embase, Cochrane, PubMed, and Scopus, focusing on studies that referenced gut microbiome and anti-diabetic medications. Included studies were randomised controlled trials, cohort studies, and case-control studies, observing recently diagnosed adult T2DM patients. The risk assessment tools used for clinical trials were ROB-2 and modified ROBINS-I for observational studies. Results The initial search provided 8528 papers, and in total, 6 studies were incorporated in this review. Study methodology varied greatly, resulting in vast heterogeneity, specifically in DNA extraction, sequencing protocols, and correlation methodologies. However, various patterns surfaced among the studies. Bifidobacterium, Bacteroides, and Lachnoclostridium stood out as three genera correlated with HbA1c% reduction in three of six studies. Conclusion Emerging evidence suggests that the gut microbiome may be associated with the efficacy of anti-diabetic medications (ADMs). However, the substantial methodological heterogeneity, relatively homogeneous study populations, and small sample sizes limit the ability to establish a robust and definitive association. Further investigation through large-scale, longitudinal studies involving diverse populations and standardised methodologies is therefore warranted to clarify the relationship between gut microbiome composition and ADM efficacy. Establishing a reproducible and clinically meaningful association could allow faecal microbiome profiling to contribute to a precision medicine approach in endocrinology. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420261432018 , identifier CRD420261432018.