Possible metformin-induced hepatotoxicity

Abstract

Background: Metformin hydrochloride is widely used for the treatment of type 2 diabetes mellitus (DM-2). To date, only 2 cases of possible metformin-induced hepatotoxicity (acute hepatitis) have been reported worldwide.

Objective: The aim of this article was to report a case of serious hepatotoxicity possibly associated with metformin use in an elderly patient with DM-2.

Methods: After receiving metformin 500 mg/d for 3 weeks, a 73-year-old Japanese woman weighing 33.5 kg with poorly controlled DM-2 presented with fatigue, jaundice, nausea, vomiting, anorexia, and abdominal pain. Laboratory analysis showed severe hepatotoxicity (elevated aspartate and alanine aminotransferases [AST and ALT, respectively], alkaline phosphatase [ALP], and total bilirubin concentrations). The history, clinical findings, laboratory features, and clinical course of this case, as well as the pharmacologic profile of metformin, are presented.

Results: Immediate hospitalization and discontinuation of metformin treatment led to improvements in liver function (decreased AST, ALT, ALP, and total bilirubin concentrations) and resolution of the presented symptoms within 3 weeks. The probability of an adverse drug reaction (ADR), as assessed using the Naranjo ADR probability scale, in this case was 4 (probable).

Conclusions: In this case of an elderly woman with DM-2 who presented with symptoms of hepatotoxicity after 3 weeks of metformin treatment, metformin appeared to have caused a mixed-type (hepatocellular and cholestatic) hepatic damage. Although rare, severe hepatotoxicity might be associated with metformin use in some cases.