Can Ozempic (semaglutide) cause elevated liver function tests (LFTs)?

Ozempic (Semaglutide) and Elevated Liver Function Tests

Yes, Ozempic (semaglutide) can cause elevated liver function tests (LFTs), though this is generally not a major concern and may actually improve in patients with underlying fatty liver disease.

Effects of Semaglutide on Liver Function

• Semaglutide has been associated with transient elevations in liver enzymes in some patients, though these are typically mild and often clinically insignificant 1
• In patients with elevated baseline ALT (men >30 IU/L; women >19 IU/L), semaglutide actually demonstrated significant reductions in ALT levels by 6-21% compared to placebo 1
• Normalization of elevated baseline ALT occurred in 25-46% of patients on semaglutide compared to only 18% on placebo 1
• Higher doses of semaglutide (1.0 mg/week) showed a 9% reduction in ALT levels compared to placebo in patients with elevated baseline ALT 1

Beneficial Effects on Liver Health

• Semaglutide treatment has been shown to significantly improve liver enzymes, reduce liver stiffness, and improve metabolic parameters in patients with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) 2
• Treatment with semaglutide for 24 weeks demonstrated significant reductions in:
  • Serum alanine transaminase (mean difference: 14.07 U/L) 2
  • Aspartate transaminase (mean difference: 6.89 U/L) 2
  • Liver fat content (mean difference: 4.97%) 2
  • Liver stiffness (mean difference: 0.96 kPa) 2
• Recent research shows that 12-month treatment with semaglutide simultaneously improves liver steatosis and fibrosis in patients with type 2 diabetes and NAFLD 3

Monitoring Recommendations

• While specific monitoring guidelines for semaglutide are not established in current guidelines, it's reasonable to follow general principles for medication monitoring 4
• For medications that may affect liver function, monitoring LFTs within the first 1-2 months of usage and every 3-4 months thereafter is conditionally recommended in clinical practice 4
• If clinically relevant elevations in LFTs are found, decreasing or temporarily holding the medication dose may be appropriate 4

Mechanism and Context

• The LFT changes observed with semaglutide appear to be related to its effects on weight and metabolic parameters, as treatment ratios for changes in ALT were not statistically significant after adjustment for weight change 1
• Semaglutide also reduces high-sensitivity C-reactive protein (hsCRP) by 25-43% versus placebo, indicating an anti-inflammatory effect that may benefit liver health 1

Adverse Effects to Consider

• The most common adverse effects of semaglutide are gastrointestinal (nausea, vomiting, dyspepsia, decreased appetite, constipation, and diarrhea) 2
• Gallbladder-related diseases have also been reported with semaglutide treatment 2
• When evaluating elevated LFTs in patients on semaglutide, it's important to rule out other common causes such as viral hepatitis, alcohol consumption, other medications with known hepatotoxicity, underlying liver disease, and biliary obstruction 5

Clinical Implications

• For patients with type 2 diabetes and NAFLD, semaglutide may actually provide liver benefits rather than concerns 3
• The improvement in liver enzymes appears to be part of semaglutide's broader metabolic benefits, which include improved glycemic control and cardiovascular outcomes 3
• In patients with diabetic nephropathy, semaglutide has shown renoprotective effects alongside metabolic improvements 6

In conclusion, while transient elevations in liver enzymes can occur with semaglutide, the medication generally has a favorable liver profile and may even improve liver health in patients with underlying fatty liver disease, which is common in the population typically prescribed this medication.