Can metformin (metformin) be initiated in a patient with mild liver dysfunction, as indicated by liver function tests in the 50s, and stable steatosis (fatty liver disease)?

From the Guidelines

Metformin can be initiated in a patient with mild liver dysfunction, as indicated by liver function tests in the 50s, and stable steatosis (fatty liver disease), as long as renal function is adequate (eGFR >30 mL/min) and the patient is closely monitored for signs of liver dysfunction or lactic acidosis. According to the most recent guidelines, metformin is a commonly used medication for type 2 diabetes and is effective in improving insulin sensitivity and reducing hepatic fat accumulation 1.

Key Considerations

• Start with a low dose of metformin, such as 500 mg once daily with a meal, and gradually increase to the target dose (typically 1000-2000 mg daily in divided doses) as tolerated.
• Monitor liver function tests (LFTs) every 3 months initially, then every 6-12 months if stable.
• Metformin is contraindicated in severe hepatic impairment (Child-Pugh C) or if LFTs are significantly elevated (typically >2.5-3 times upper limit of normal).
• If the patient experiences worsening of liver function or symptoms such as nausea, abdominal pain, or jaundice, metformin should be discontinued.

Benefits and Risks

• Metformin has been shown to reduce the risk of microvascular complications, cardiovascular events, and death in patients with type 2 diabetes 1.
• However, metformin may cause gastrointestinal intolerance, vitamin B12 deficiency, and worsening of symptoms of neuropathy 1.
• The risk of lactic acidosis is very rare, but metformin should be used with caution in patients with impaired renal function 1.

Monitoring and Follow-up

• Regular monitoring of LFTs, renal function, and vitamin B12 levels is recommended.
• Patients should be educated on the signs and symptoms of lactic acidosis and liver dysfunction, and instructed to seek medical attention if they experience any of these symptoms.

From the FDA Drug Label

Hepatic impairment —Patients with hepatic impairment have developed cases of metformin- associated lactic acidosis. This may be due to impaired lactate clearance resulting in higher lactate blood levels Therefore, avoid use of metformin hydrochloride tablets in patients with clinical or laboratory evidence of hepatic disease.

Metformin should not be initiated in a patient with mild liver dysfunction, as indicated by liver function tests in the 50s, and stable steatosis (fatty liver disease), due to the risk of metformin-associated lactic acidosis in patients with hepatic impairment 2 2.

From the Research

Metformin Initiation in Patients with Mild Liver Dysfunction

• Metformin can be initiated in patients with mild liver dysfunction, as indicated by liver function tests in the 50s, and stable steatosis (fatty liver disease) 3.
• The literature suggests that metformin does not appear to cause or exacerbate liver injury and is often beneficial in patients with nonalcoholic fatty liver disease 3.
• Nonalcoholic fatty liver disease frequently presents with transaminase elevations but should not be considered a contraindication to metformin use 3.

Liver Function Tests and Metformin Therapy

• Withholding metformin from patients with abnormal transaminases or routinely monitoring transaminases before or during metformin treatment is not supported 3.
• Metformin is not considered intrinsically hepatotoxic, and cirrhosis can exist in the face of normal liver transaminases 3.
• Identifying patients with cirrhosis before initiating metformin seems prudent, as patients with cirrhosis, particularly those with encephalopathy, may have arterial hypoxemia, which heightens the risk of developing lactic acidosis 3.

Metformin's Effects on Liver Steatosis

• Metformin treatment has been shown to be effective at alleviating hepatic lipogenesis in animal models of NAFLD 4.
• Evidence exists regarding the benefits of metformin for NAFLD in preclinical studies, with reports on the efficacy of metformin in adult NAFLD patients having some discrepancies regarding changes in liver biochemistry and hepatic fat content 4.
• Metformin may have equally affected liver function tests, HOMA-IR, lipid profile, and liver fat content in NAFLD patients 5.

Management of Metabolic Dysfunction Associated Steatotic Liver Disease

• Metabolic dysfunction associated steatotic liver disease is the most common cause of chronic liver disease in the United States with rapidly rising prevalence 6.
• Screening is now recommended for patients at risk for significant liver fibrosis in primary care and endocrine settings, along with clear guidance for management of metabolic comorbidities 6.
• Providers should shift away from past practices of utilizing liver tests alone as a screening tool and shift towards fibrosis screening in patients at risk for significant fibrosis 6.