Gut microbiome disparities reflect type 2 diabetes progression and medication status

Type 2 diabetes mellitus (T2D) prevalence is rapidly increasing in India, yet microbiome signatures linked to disease progression and oral antidiabetic therapy remain underexplored. We performed full-length 16S rRNA sequencing of fecal samples from prediabetics (PDs), untreated newly diagnosed T2D (UKT2D), and clinically diagnosed T2D patients (KT2D), alongside biochemical, anthropometric, and medication data. Despite comparable glycemic control and insulin resistance between UKT2D and KT2D groups, gut microbial diversity was significantly reduced in KT2D, coinciding with antidiabetic drug use, primarily metformin. <i>Lactobacillus</i> abundance increased with disease progression, while Clostridium_sensu_stricto_1 was associated with glucose homeostasis and insulin sensitivity. β diversity differed only between controls and PD, with no other pairwise differences. Collectively, these results indicate that T2D progression and oral antidiabetic medications remodel the gut microbiome in this south Asian cohort and highlight the need to reassess antidiabetic treatment efficacy using larger longitudinal studies.