From the Guidelines
Semaglutide should be used with caution in patients with liver cirrhosis, particularly in those with Child-Pugh B cirrhosis, and is contraindicated in patients with Child-Pugh C cirrhosis. When considering the use of semaglutide in patients with liver cirrhosis, it is essential to weigh the potential benefits of weight loss and improved metabolic control against the potential risks of worsening liver function. According to the EASL clinical practice guidelines on liver transplantation 1, GLP-1 receptor agonists, such as semaglutide, are contraindicated in patients with Child-Pugh C cirrhosis and should be used with caution in Child-Pugh B cirrhosis.
Some key points to consider when using semaglutide in patients with liver cirrhosis include:
- Starting with the lowest dose and titrating slowly while monitoring liver function tests regularly
- Close monitoring for potential side effects, including nausea, vomiting, and diarrhea, which may be more pronounced in patients with liver disease
- Discontinuing the medication if the patient experiences worsening liver function tests or signs of hepatic decompensation
- Considering alternative weight loss strategies, such as bariatric surgery, in patients with severe cirrhosis or those who are not candidates for semaglutide therapy
The use of semaglutide in patients with liver cirrhosis requires careful consideration of the potential risks and benefits, as well as close monitoring and management to minimize the risk of adverse effects. As noted in the EASL guidelines 1, the management of obesity is crucial in patients with liver cirrhosis, and semaglutide may be a useful therapeutic option in selected patients with mild to moderate cirrhosis. However, the decision to use semaglutide in patients with liver cirrhosis should be made on a case-by-case basis, taking into account the individual patient's clinical characteristics and medical history.
From the FDA Drug Label
8.7 Hepatic Impairment No dose adjustment of OZEMPIC is recommended for patients with hepatic impairment. In a study in subjects with different degrees of hepatic impairment, no clinically relevant change in semaglutide pharmacokinetics (PK) was observed [see Clinical Pharmacology (12.3)].
Semaglutide with liver cirrhosis:
- No dose adjustment is recommended for patients with hepatic impairment, including liver cirrhosis.
- The pharmacokinetics of semaglutide were evaluated in patients with different degrees of hepatic impairment, and no clinically relevant change was observed 2.
- Key points:
- No dose adjustment needed
- Hepatic impairment does not affect semaglutide pharmacokinetics
- Caution should still be exercised when using semaglutide in patients with liver cirrhosis, as the clinical evidence may be limited.
From the Research
Semaglutide and Liver Cirrhosis
- Semaglutide is a glucagon-like peptide-1 analogue that has been investigated for its efficacy and safety in patients with non-alcoholic steatohepatitis (NASH)-related cirrhosis 3.
- A randomized, placebo-controlled phase 2 trial found that semaglutide did not significantly improve fibrosis or achievement of NASH resolution versus placebo in patients with NASH and compensated cirrhosis 3.
- However, another study found that semaglutide was associated with a lower risk of major adverse liver outcomes (MALO) compared to other antidiabetic medications in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes 4.
Safety and Pharmacokinetics
- Patients with cirrhosis have altered pharmacokinetics and pharmacodynamics of medicines, which can increase the risk of adverse events 5.
- Semaglutide has been shown to be safe and well-tolerated in patients with cirrhosis, with no significant differences in adverse events or serious adverse events compared to placebo 3.
- The most common adverse events associated with semaglutide were nausea, diarrhea, and vomiting 3.
Effects on Liver Function
- Semaglutide has been shown to improve liver function in patients with NAFLD and type 2 diabetes, with reductions in liver steatosis and fibrosis indices 6, 7.
- A study found that semaglutide reduced the Controlled Attenuation Parameter (CAP) score, E fibrosis score, NAFLD fibrosis score, and Fibrosis-4 (FIB-4) score in patients with type 2 diabetes and NAFLD 6.
- Another study found that semaglutide improved biomarkers of metabolic-associated fatty liver disease (MAFLD), including the hepatic steatosis index (HSI) and FIB-4 index, in patients with diabetes and obesity 7.
Vascular and Endothelial Function
- Semaglutide has been shown to improve vascular and endothelial function in patients with type 2 diabetes and NAFLD, with reductions in central systolic blood pressure, augmentation index, and pulse wave velocity 6.
- The improvements in vascular and endothelial function were correlated with reductions in liver steatosis and fibrosis indices 6.