Metagenomic analysis reveals crosstalk between gut microbiota and glucose-lowering drugs targeting the gastrointestinal tract in Chinese patients with type 2 diabetes: a 6 month, two-arm randomised trial

• Published in: Diabetologia 2022-10, Vol.65 (10), p.1613-1626
• Main Authors: Zhang, Xiuying, Ren, Huahui, Zhao, Cuiling, Shi, Zhun, Qiu, Li, Yang, Fangming, Zhou, Xianghai, Han, Xueyao, Wu, Kui, Zhong, Huanzi, Li, Yufeng, Li, Junhua, Ji, Linong
• Format: Article
• Language: English
• Subjects: Acarbose; Acarbose - therapeutic use; Blood Glucose - metabolism; Body weight; China; Computed tomography; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2; Digestive system; Drug delivery; Drug development; Drug efficacy; Drugs; Ecosystem; Feces; Gastrointestinal Microbiome; Gastrointestinal tract; Gastrointestinal Tract - metabolism; Glipizide - therapeutic use; Glucagon; Glucagon-like peptide 1; Glucagon-Like Peptide 1 - therapeutic use; Glucose; Human Physiology; Humans; Hypoglycemic Agents - pharmacology; Internal Medicine; Intestinal microflora; Medicine; Medicine & Public Health; Metabolic Diseases; Metagenomics; Microbiota; Overweight; Patients; Statistical analysis; Vildagliptin - therapeutic use
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-022-05768-5

Aims/hypothesis The use of oral glucose-lowering drugs, particularly those designed to target the gut ecosystem, is often observed in association with altered gut microbial composition or functional capacity in individuals with type 2 diabetes. The gut microbiota, in turn, plays crucial roles in the modulation of drug efficacy. We aimed to assess the impacts of acarbose and vildagliptin on human gut microbiota and the relationships between pre-treatment gut microbiota and therapeutic responses. Methods This was a randomised, open-labelled, two-arm trial in treatment-naive type 2 diabetes patients conducted in Beijing between December 2016 and December 2017. One hundred participants with overweight/obesity and newly diagnosed type 2 diabetes were recruited from the Pinggu Hospital and randomly assigned to the acarbose ( n =50) or vildagliptin ( n =50) group using sealed envelopes. The treatment period was 6 months. Blood, faecal samples and visceral fat data from computed tomography images were collected before and after treatments to measure therapeutic outcomes and gut microbiota. Metagenomic datasets from a previous type 2 diabetes cohort receiving acarbose or glipizide for 3 months were downloaded and processed. Statistical analyses were applied to identify the treatment-related changes in clinical variables, gut microbiota and associations. Results Ninety-two participants were analysed. After 6 months of acarbose ( n =44) or vildagliptin ( n =48) monotherapy, both groups achieved significant reductions in HbA 1c (from 60 to 46 mmol/mol [from 7.65% to 6.40%] in the acarbose group and from 59 to 44 mmol/mol [from 7.55% to 6.20%] in the vildagliptin group) and visceral fat areas (all adjusted p values for pre–post comparisons