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Effects of metformin, acarbose, and sitagliptin monotherapy on gut microbiota in Zucker diabetic fatty rats
  1. Minchun Zhang1,
  2. Rilu Feng1,
  3. Mei Yang1,
  4. Cheng Qian1,
  5. Zheng Wang2,
  6. Wei Liu1,
  7. Jing Ma1
  1. 1Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  2. 2Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  1. Correspondence to Dr Jing Ma; cherry1996{at}; Dr Wei Liu; sue_liuwei{at}


Objective Recent studies have demonstrated that gut microbiota was closely related to metabolic disorders such as type 2 diabetes. Oral antidiabetic medications including metformin, acarbose and sitagliptin lowered blood glucose levels via acting on the gastrointestinal tract. The aim of the study was to observe the comparisons among those medications on gut microbiota composition.

Research design and methods Zucker diabetic fatty rats (n=32) were randomly divided into four groups, and had respectively gastric administration of normal saline (control), metformin (215.15 mg/kg/day), acarbose (32.27 mg/kg/day), or sitagliptin (10.76 mg/kg/day) for 4 weeks. Blood glucose levels were measured during an intragastric starch tolerance test after the treatments. 16S rRNA gene sequencing was used to access the microbiota in the fecal samples.

Results Metformin, acarbose, and sitagliptin monotherapy effectively decreased fasting and postprandial blood glucose levels (p<0.001). Acarbose group displayed specific cluster and enterotype mainly composed by Ruminococcus 2 while Lactobacillus was the dominant bacterium in the enterotype of the other three groups. The relative abundance of genera Ruminococcus 2 and Bifidobacterium was dramatically higher in acarbose group. Metformin and sitagliptin increased the relative abundance of genus Lactobacillus. Metagenomic prediction showed that the functional profiles of carbohydrate metabolism were enriched in acarbose group.

Conclusions Metformin, acarbose and sitagliptin exerted different effects on the composition of gut microbiota and selectively increased the beneficial bacteria. Supplementation with specific probiotics may further improve the hypoglycemic effects of the antidiabetic drugs.

  • Metformin
  • acarbose
  • sitagliptin
  • type 2 diabetes
  • gut microbiota

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  • MZ and RF contributed equally.

  • Contributors MCZ analyzed the data, prepared the figures and wrote the manuscript. RLF conducted the animal experiments and evaluated the data. MY performed the animal experiments. CQ performed the fecal DNA extraction. WL and ZW contributed to the study design and reviewed the manuscript. JM is the guarantor of this study who has full access to all the data to guarantee the accuracy and integrity of the data.

  • Funding This work was supported by the National Natural Science Foundation of China (grant number NSFC81670728), the Shanghai Municipal Education Commission–Gaofeng Clinical Medicine Grant Support (grant number 20181807) and the Clinical Research Funding in Renji Hospital affiliated to Shanghai Jiao Tong University (grant number PYZY16-020).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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