Is Ozempic (semaglutide) safe for patients with liver cirrhosis?

Semaglutide (Ozempic) in Liver Cirrhosis: Safety Considerations

GLP-1 receptor agonists like semaglutide (Ozempic) can be used safely in patients with compensated (Child-Pugh Class A) cirrhosis but should be avoided in decompensated cirrhosis. 1

Safety Profile in Different Stages of Cirrhosis

• GLP-1 receptor agonists, including semaglutide, are considered safe for use in patients with Child-Pugh Class A (compensated) cirrhosis 1
• Insulin is the preferred glucose-lowering agent for patients with decompensated cirrhosis due to lack of robust safety data for GLP-1 receptor agonists in this population 1
• A recent 48-week study suggested that GLP-1 receptor agonists may be safe in patients with NASH and compensated cirrhosis, but more long-term data is needed 1

Pharmacokinetic Considerations

• Hepatic impairment does not significantly impact the pharmacokinetics of semaglutide according to FDA data 2
• Semaglutide is primarily eliminated through metabolism following proteolytic cleavage and beta-oxidation, with only about 3% excreted unchanged in urine 2
• The primary concern with semaglutide in cirrhosis is not altered drug metabolism but rather potential clinical effects on the compromised liver 3

Benefits in Liver Disease

• Semaglutide has shown promise in treating non-alcoholic steatohepatitis (NASH), with resolution of steatohepatitis in 59% of patients in a 72-week study 4
• It significantly slowed progression of liver fibrosis (4.9% with highest dose vs 18.8% on placebo) 1
• These benefits must be weighed against potential risks in the cirrhotic population 5

Risks and Warnings

• There have been case reports of liver decompensation in patients with NASH-cirrhosis treated with semaglutide, particularly related to rapid weight loss 5
• One documented case showed development of ascites and hepatic encephalopathy with an increase in MELD-Na score from 11 to 22 after rapid weight loss on semaglutide 5
• Rare cases of progressive cholestasis and biliary cirrhosis have been reported after initiating oral semaglutide 6

Recommendations for Clinical Practice

• For patients with compensated (Child-Pugh A) cirrhosis:

  • Semaglutide can be used with regular monitoring of liver function 1
  • Start with lower doses and titrate slowly to minimize gastrointestinal side effects 4
  • Monitor for rapid weight loss, which could precipitate decompensation 5

• For patients with decompensated cirrhosis:

  • Avoid semaglutide and other GLP-1 receptor agonists 1
  • Insulin is the preferred glucose-lowering agent in this population 1
  • Consider nutritional status carefully, as these patients often have sarcopenia 1

• For all cirrhotic patients on semaglutide:

  • Monitor for signs of liver decompensation (ascites, encephalopathy, jaundice) 5
  • Ensure adequate protein intake (1.2-1.5 g/kg/day) to prevent sarcopenia during weight loss 1
  • Consider stopping the medication if liver function deteriorates 5

Alternatives for Patients with Cirrhosis

• Metformin can be used in compensated cirrhosis with preserved renal function but should be avoided in decompensated cirrhosis due to risk of lactic acidosis 1
• SGLT2 inhibitors may be used in Child-Pugh class A and B cirrhosis with appropriate monitoring 1
• Sulfonylureas should be avoided in hepatic decompensation due to risk of hypoglycemia 1

In conclusion, while semaglutide shows promise for NASH treatment, caution is warranted in cirrhotic patients. The medication appears safe in compensated cirrhosis but should be avoided in decompensated disease, with close monitoring for signs of liver deterioration in all cirrhotic patients receiving this therapy.