Effects of metformin, acarbose, and sitagliptin monotherapy on gut microbiota in Zucker diabetic fatty rats

Oct 24, 2019BMJ open diabetes research & care

How Metformin, Acarbose, and Sitagliptin Alone Change Gut Bacteria in Diabetic Rats

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Abstract

Metformin, acarbose, and sitagliptin significantly lowered fasting and postprandial blood glucose levels (p<0.001).

Acarbose administration resulted in a unique microbiota cluster and enterotype distinct from the other treatments.
The abundance of certain beneficial bacteria was notably increased in the acarbose group.
Metformin and sitagliptin treatment led to a rise in the abundance of Lactobacillus.
Functional profiles related to carbohydrate metabolism were enriched in the acarbose group.
These medications may differentially affect gut microbiota composition, suggesting potential for probiotic supplementation to enhance hypoglycemic effects.

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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 bywhilewas the dominant bacterium in the enterotype of the other three groups. The relative abundance of generaandwas 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. Ruminococcus 2Lactobacillus Ruminococcus 2Bifidobacterium

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.

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Effects of metformin, acarbose, and sitagliptin monotherapy on gut microbiota in Zucker diabetic fatty rats

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