METFORMIN – INDUCED DIARRHEA AS DELAYED ADVERSE REACTION AFTER MANY YEARS OF USE – CASE REPORT

  • Marija Stepanović Lundbeck Export A/S Belgrade
  • Dragan Milovanović Department for clinical pharmacology KC Kragujevac
Keywords: delayed, adverse reaction, Diarrhea, Metformin,

Abstract


Background: Metformin is an oral antidiabetic drug from bigvanides group. It does not cause hypoglycemia, and therefore has found its place as a first-line therapy in type 2 diabetes. It is used both as mono-therapy and as adjunctive therapy with other anti-diabetics and insulin. Some of the most common adverse reactions of metformin are: gastrointestinal upset, diarrhea, nausea, flatulence and vomiting. Adverse reactions usually occur at the beginning of the therapy.

Aim: To show the potential of metformin to cause delayed adverse effects after years of use.

Case report: A sixty-four-year-old woman with type 2 diabetes was treated with metformin for ten years. Several months ago she started to have diarrhea with fluctuating character and intensity. She lost 20 pounds in weight without a special diet.  Gastroenterologist and surgeon were consulted, but the cause of diarrhea was not established. A clinical pharmacologist was consulted next to evaluate possible relationship between diarrhea and medication. According to the relevant literature, metformin had the highest prevalence of diarrhea among the medication that was taken by the patient. Therefore, the strategy of discontinuation and then re-challenge by the drug was used. Two days after the metformin was discontinued the diarrhea stopped, and five days later, after the patient was re-challenged by the drug, diarrhea reappeared, with similar characteristics as before.

Conclusion: Metformin-induced diarrhea usually occurs at the beginning of the treatment. However, it could have delayed appearance, even after many years of continuous use of metformin.

References

Medić-Zamaklar M. Primena oralnih hipoglikemijskih agenasa u lečenju diabetes mellitusa, Diabetes melli-tus-odabrana poglavlja 1, Beograd 1993; 127-41.

John HB Scarpello and Harry CS Howlett, Metformin therapy and clinical uses Diabetes and Vascular Dise-ase Research 2008; 5(3): 157-67.

Giannarelli R, Aragona M, Coppelli A, Del Prato S. Reducing insulin resistance with metformin: the evidence today. Diabetes Metab 2003; 29: 6S28-35.

Hundal RS, Krssak M, Dufour S et al. Mechanism by which metformin reduces glucose production in type 2 diabetes. Diabetes 2000; 49: 2063-9.

Amer Shakil, Robert J. Church, Shobha S. Rao, Ga-strointestinal Complications of Diabetes. Am Fam Physician 2008 ; 77(12): 1697-72.

Bytzer P,Talley NJ,Jones MP, Horowitz M Oral hypoglycaemic drugs and gastrointestinal symptoms in diabetes mellitus. Aliment Pharmacol Ther 2001; 15(1): 137-4.

Naranjo skor. (posećeno u oktobru 2012. na: liver-tox.nih.gov/Naranjo.html)

Davidson MB, Peters AL. An overview of metformin in the treatment of type 2 diabetes mellitus. Am J Med 1997; 102: 99-110.

Haupt E, Knick B, Koschinsky T, Liebermeister H, Schneider J, Hirche H. Oral antidiabetic combination therapy with sulphonylureas and metformin. Diabetes Metab 1991; 17: 224-31.

Dandona P, Fonseca V, Mier A, Beckett AG. Diarrhea and metformin in a diabetic clinic. Diabetes Care 1983; 6: 472-4.

Scarpello JH, Hodgson E, Howlett HC. Effect of met-formin on bile salt circulation and intestinal motility in type 2 diabetes mellitus. DiabetMed 1998; 15: 651-6.

Carter D, Howlett HCS, Wiernsperger NF, Bailey CJ. Differential effects of metformin on bile salt absorption from the jejunum and ileum. Diabetes Obesity Metab 2003; 5: 120-5.

Foss MT, Clement KD. Metformin as a cause of late-onset chronic diarrhea. Pharmacotherapy 2001; 21(11): 1422-4.

Published
2013/02/20
Section
Review