Severe and long-lasting diarrhea not recognized as adverse effect of metformin: A description of three elderly patients

Background.- As a result of the United Kingdom Prospective Diabetes Study (UKPDS), metformin became the first choice drug for patients with diabetes. In 2009 three patients were admitted to our geriatric department for analysis of disabling long-lasting diarrhea. Metformin as causative agent was considered. The association was studied in Vigibase, the adverse drug reaction (ADR) database of the WHO Collaborating Centre for Internatinal Drug Monitoring, the Uppsala Monitoring Centre (WHO-UMC). Methods.- Three cases of long lasting disabling diarrhea in patients using metformin are described. In a case/non-case analysis, the strength of association between reported cases with diarrhea and the use of metformin in Vigibase was established by calculating a reported odds ratio, adjusted for possible confounding by concomitant medication. Results.- Three female patients, aged 86, 79 and 83 were referred to our geriatric department because of disabling long-lasting diarrhea. The first patient had an unnecessary colonoscopy, the second patient was hospitalized for further observation and the third patient was hospitalized because of serious hypomagnesaemia and hypocalcaemia caused by the long-lasting diarrhea. In the first two patients metformin had been overlooked as the cause of the diarrhea, in the third patient the diarrhea had been accepted as an adverse effect. In all three patients the diarrhea stopped completely after cessation of metformin. In Vigibase, metformin is disproportionally associated with diarrhea (corrected reporting odds ratio 5.60 [95%CI 5.3-5.9]). Discussion.- Although diarrhea is a well-known adverse effect of metformin, it is not always recognized. The mechanism by which metformin causes diarrhea is not fully understood. Postulated mechanisms include a direct effect of metformin on the intestinal tissue, leading to increased motility, malabsorption or both. Conclusion.- Metformin can cause disabling diarrhea even in low dose. We suggest that a metformin free period should be considered in every patient with diarrhea.