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

Abstract

ObjectiveRecent 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 methodsZucker 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.ResultsMetformin, acarbose, and sitagliptin monotherapy effectively decreased fasting and postprandial blood glucose levels (p<0.001). Acarbose group displayed specific cluster and enterotype mainly composed byRuminococcus 2whileLactobacilluswas the dominant bacterium in the enterotype of the other three groups. The relative abundance of generaRuminococcus 2andBifidobacteriumwas 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.ConclusionsMetformin, 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.

The DPP-4 inhibitor sitagliptin alters the gut microbiota and prevents neuronal damage of hippocampus in STZ induced type 2 diabetic rats

“…Our objective was to determine whether sitagliptin treatment played an important role in returning the gut microbiota back to the normal. Moreover, the sitagliptin-treated rats displayed changed microbial diversity compared to diabetic rats, which was in accordance with the previous study [35].…”

Gut Microbiota Dysbiosis in Patients with Biopsy-Proven Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study in Taiwan

“…Recently, emerging evidence suggests that oral antidiabetic drugs, such as metformin, acarbose, and sitagliptin monotherapy, may respectively alter the composition of gut microbiota and selectively increased the beneficial bacteria [37]. In the present study, there was a total of 12 subjects with diabetes mellitus (two in healthy controls; three in NAFL group; seven in NASH group).…”

Effects of Metformin and Sitagliptin Monotherapy on Expression of Intestinal and Renal Sweet Taste Receptors and Glucose Transporters in a Rat Model of Type 2 Diabetes

“…They were fed a Purina 5008 diet (56.5 % carbohydrate, 26.8 % protein and 16.7 % fat). The animals were housed in Shanghai SLAC Laboratory Animal Co., Ltd. (Shanghai, China, SYXK2017-0008) and the ambient environment was described in a previous study [26]. Body weight and blood glucose were monitored weekly.…”

“…The rats were randomly divided into three groups (8 rats in each group), each of which was gavage fed with normal saline as a control (CON group), metformin (Sino-American Shanghai Squibb Pharmaceuticals Ltd., H20023370, 215.15 mg/ kg body weight/day dissolved in distilled water; MET group), or sitagliptin (Merck, Sharp & Dohme Ltd., J20140095, 10.76 mg/kg body weight/day, dissolved in distilled water; SIT group). The doses of antidiabetic agents were chosen to be equivalent to metformin 1000 mg twice daily and sitagliptin 100 mg daily, using the formula: [26,27].…”