The Microbial Regulation Spectrum of Metformin in Patients With Type 2 Diabetes: An Individual-Based Meta-Analysis of 1431 Participants

Abstract Context The gut microbiota plays a significant role in metformin efficacy and therapeutic response. However, studies often have produced inconsistent outcomes. Objective To gain a more comprehensive understanding of the transformation of gut microbiota in persons with diabetes and the subsequent modifications following metformin intervention. Data Sources Seven databases were searched, from the inception of each database up to October 30, 2024. The raw sequence reads of 9 available datasets were downloaded from the National Center for Biotechnology Information (NCBI). Study Selection The process of selecting and assessing papers for this study was meticulously managed by 2 authors, working independently to screen and evaluate each publication. Data Extraction For the data extraction phase, a standardized form was employed, capturing critical details. Data Synthesis Metformin significantly boosts the presence of Akkermansia and short-chain fatty acid (SCFA)-producing bacteria, such as Pseudobutyrivibrio, Oribacterium, and Anaerotruncus, and it simultaneously diminishes pathogenic bacteria, including Enterobacillus, Gemmobacter, Shinella, Klebsiella, and Enterocloster. In addition, Bifidobacterium and Blautia were increased in patients with type 2 diabetes (T2D) but restored to near normal levels by metformin, and this alteration is region-specific. Conclusion Our analysis delivers more concrete evidence regarding the shifts in gut microbiota following metformin treatment, significantly enriching our understanding of the interplay between gut microbiome dynamics and the management of T2D.