From the Guidelines
Metformin remains the first-line therapy for most patients with mild to moderate liver disease, though it should be avoided in severe hepatic impairment or active liver injury, as recommended by the most recent guidelines 1. When considering the management of diabetes in patients with liver disease, it's crucial to weigh the benefits and risks of each medication, prioritizing those that minimize hepatic processing and have a safer profile in liver impairment.
- Metformin, as stated, is generally safe for mild to moderate liver disease but should be used cautiously or avoided in severe cases due to the risk of lactic acidosis 1.
- DPP-4 inhibitors like sitagliptin and linagliptin are well-tolerated, with linagliptin preferred due to its lack of need for dose adjustment in liver disease 1.
- GLP-1 receptor agonists, such as liraglutide and semaglutide, can be used cautiously in mild to moderate liver impairment, as they have shown benefits in glycemic control with a relatively safe liver profile 1.
- Insulin is the safest option for patients with severe liver disease, as it is not metabolized by the liver and can be adjusted based on glucose monitoring, thus providing a flexible and safe glycemic control option 1.
- Medications to avoid or use with extreme caution include thiazolidinediones due to the risk of hepatotoxicity, sulfonylureas because of the risk of hypoglycemia due to impaired hepatic metabolism, and SGLT-2 inhibitors in advanced liver disease 1. Regular monitoring of liver function is essential, and medication choices should be reassessed if liver function deteriorates, emphasizing the need for a dynamic and patient-centered approach to managing diabetes in the context of liver disease. The choice of medication should prioritize minimizing morbidity, mortality, and improving the quality of life for patients with diabetes and liver disease, guided by the most recent and highest quality evidence available 1.
From the FDA Drug Label
Patients with Hepatic Impairment In subjects with hepatic impairment (Child-Pugh classes A, B, and C), mean Cmax and AUC of saxagliptin were up to 8% and 77% higher, respectively, compared to healthy matched controls following administration of a single 10 mg dose of saxagliptin. The corresponding Cmax and AUC of the active metabolite were up to 59% and 33% lower, respectively, compared to healthy matched controls. These differences are not considered to be clinically meaningful
- Saxagliptin may be used in patients with liver disease, as the differences in pharmacokinetics are not considered clinically meaningful.
- No dosage adjustment is necessary for patients with hepatic impairment. 2
From the Research
Diabetic Medications Safe for Use in Patients with Liver Disease
- Metformin is considered safe for use in patients with liver disease, as it has been shown to have positive effects on cirrhosis and anti-tumoral properties, and can help prevent the development of hepatocellular carcinoma 3, 4, 5.
- Incretin-based therapies, such as dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, have been found to be safe for use in patients with liver disease, with only mild changes in pharmacokinetic characteristics observed in patients with hepatic impairment 6.
- Sitagliptin, a DPP-4 inhibitor, has been shown to be effective in improving metabolic parameters and liver test results in patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease when added to metformin therapy 7.
Specific Medications and Their Effects on Liver Disease
- Metformin: has been shown to improve insulin resistance and dyslipidaemia, commonly associated with liver diseases, and has a chemopreventive role against hepatocellular carcinoma in patients with diabetes and chronic liver disease 3, 4.
- DPP-4 inhibitors (e.g. sitagliptin): have been found to be safe for use in patients with liver disease, with mild changes in pharmacokinetic characteristics observed in patients with hepatic impairment, and may have beneficial effects on nonalcoholic fatty liver disease 6, 7.
- GLP-1 receptor agonists: have a renal excretion rather than liver metabolism, and have been found to be safe for use in patients with liver disease, with no significant changes in liver enzymes reported in clinical trials 6.