From the FDA Drug Label
Cholestatic, hepatocellular, and mixed hepatocellular liver injury have been reported with postmarketing use of metformin.
Metformin can cause elevated liver enzymes, as evidenced by reports of liver injury in postmarketing use.
- The specific types of liver injury reported include:
- Cholestatic liver injury
- Hepatocellular liver injury
- Mixed hepatocellular liver injury 1
From the Research
Metformin is not typically associated with significant liver damage and can be beneficial for patients with nonalcoholic fatty liver disease, although rare cases of metformin-induced liver injury have been reported. The majority of patients taking metformin do not experience significant liver problems, and the medication is generally considered safe for the liver compared to many other diabetes medications 2. When elevations in liver enzymes do occur with metformin, they are typically mild and transient, often resolving without discontinuation of the medication. However, patients with pre-existing liver disease should use metformin with caution, and regular monitoring of liver function is recommended, especially during the initial months of treatment 3.
Some studies have suggested that metformin may have a protective effect on the liver, with high-dose metformin activating AMPK by inhibiting mitochondrial complex 1, and low-dose metformin activating lysosomal AMPK through PEN2, which can reduce fatty acid synthesis, inhibit tumor proliferation and metastasis, and reshape the tumor microenvironment 2. Additionally, metformin can reduce ROS production by inhibiting mitochondrial complex 1, which can reduce liver damage.
It is essential for patients to be aware of the potential rare side effects of metformin, including liver injury, and to contact their healthcare provider promptly if they experience symptoms like unusual fatigue, abdominal pain, dark urine, or yellowing of the skin or eyes while taking metformin 4, 5. For most patients with type 2 diabetes, the benefits of metformin therapy significantly outweigh the small risk of liver enzyme elevations.
Key points to consider:
- Metformin is generally safe for the liver and can be beneficial for patients with nonalcoholic fatty liver disease
- Rare cases of metformin-induced liver injury have been reported
- Patients with pre-existing liver disease should use metformin with caution and regular monitoring of liver function
- Metformin may have a protective effect on the liver by reducing fatty acid synthesis and inhibiting tumor proliferation
- Patients should be aware of the potential rare side effects of metformin and contact their healthcare provider promptly if they experience symptoms of liver injury.