BMJ Open Diabetes Research and Care 2020-Mar
Mouse model of metformin-induced diarrhea.
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RESEARCH DESIGN AND METHODS
Using mouse models, we tried to develop an evaluation system for metformin-induced diarrhea to improve diarrheal symptoms in patients with diabetes. Healthy (C57BL/6J) and diabetic obese (db/db) mice were subjected to a stepwise dose escalation of metformin (250 mg/kg/day (125 mg/kg twice daily oral dose)-1000 mg/kg/day (500 mg/kg twice daily oral dose)), and fecal moisture contents and their score were monitored. To evaluate anti-diarrheal medications, wood creosote (a traditional medicine) was tested. Several groups of enterobacteria in fresh feces were examined by using PCR.RESULTS
1000 mg/kg/day (four times maximal effective dose) of metformin significantly increased fecal moisture content. Although no symptoms of diarrhea were observed in healthy C57BL/6J mice, the same dose of metformin induced severe diarrhea in diabetic obese db/db mice. A reduction in PCR signals for the Firmicutes group was associated with metformin-induced diarrhea. Wood creosote reduced diarrhea (high water-content) without affecting metformin's efficacy or enterobacterial flora levels.CONCLUSIONS
We have created the first animal model of metformin-induced diarrhea using db/db mice, which will provide better quality of life for patients suffering from diarrhea caused by metformin.