Introduction: Metformin is considered the initial oral pharmacotherapy of choice for the treatment of hyperglycemia in Type 2 Diabetes Mellitus (T2DM). Although safe in the vast majority of the population, rare side effects will come to light as the prevalence of T2DM continues to rise. We present a case of metformin induced hepatotoxicity.
Case Description/Methods: A 75-year-old male with T2DM, on metformin therapy, presented with a 1-month history of fatigue, nausea, vomiting, anorexia, and generalized abdominal pain. He had no preexisting liver disease or prior abnormal liver labs. He denied current use of alcohol, toxins, over the counter agents, herbal products, or new prescription medications. Of note, his metformin dose had been recently increased from 500mg to 1000mg twice daily a few weeks prior to presentation.
On admission, laboratory work up was remarkable for a mixed hepatocellular and cholestatic pattern of liver injury as shown in table 1. Abdominal imaging was negative for evidence of cirrhosis, portal hypertension, hepatic steatosis, or congestion. An extensive evaluation for other etiologies of acute hepatitis were unremarkable.
Metformin was discontinued. Subsequently, patient’s liver enzymes improved, the presenting symptoms resolved, and he was discharged in a stable condition. He followed up outpatient four weeks later and was found to be doing well with normalization of liver enzymes.
Discussion: Drug induced liver injury (DILI) is a well established problem and accounts for nearly 10% of all cases of acute hepatitis. Although common, diagnosing DILI can be difficult as no specific serum biomarkers or tests are available to reliably attribute liver injury to a drug. This can be especially challenging when hepatotoxicity is caused by a medication that is not considered intrinsically hepatotoxic such as metformin. In this case, a diabetic patient presented with symptoms of acute hepatitis after an increase in metformin dose, the diagnosis of metformin-induced hepatotoxicity was supported by the causal relationship between an increase in metformin and the onset of liver injury, exclusion of all other causes of liver injury, and recovery of liver function on discontinuation of metformin.
With the rising burden of T2DM worldwide, rare side effects of commonly used anti-diabetic medications will continue to emerge. Through our case report we aim to make clinicians aware of one such reaction, metformin induced severe idiosyncratic acute liver injury.
Total Bilirubin
3.4mg/dl
Aspartate aminotransferase
3,241 units/L
Alanine aminotransferase
3,870 units/L
Alkaline Phosphatase
190 units/L
Table: (Table 1) Laboratory workup on admission was remarkable for a mixed hepatocellular and cholestatic patter of liver injury.
Disclosures:
Arooj Mian indicated no relevant financial relationships.
Baha Aldeen Bani Fawwaz indicated no relevant financial relationships.
Gurdeep Singh indicated no relevant financial relationships.
Aimen Farooq indicated no relevant financial relationships.
Ayman Koteish indicated no relevant financial relationships.
Arooj Mian, MD, Baha Aldeen Bani Fawwaz, MBBS, Gurdeep Singh, DO, Aimen Farooq, MD, Ayman Koteish, MD. D0532 - Metformin-Induced Acute Hepatitis, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.