Is Rybelsus (semaglutide) contraindicated in MAFLD (Metabolic Associated Fatty Liver Disease)?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: June 24, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Rybelsus (semaglutide) is not contraindicated in MAFLD (Metabolic Associated Fatty Liver Disease) and can be used for its approved indications, such as type 2 diabetes and obesity, as it improves cardiometabolic outcomes. According to the latest clinical practice guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD) 1, glucagon-like peptide 1 receptor agonists (GLP1RAs), including semaglutide, are safe to use in MASH (including compensated cirrhosis) and should be used for their respective indications. The guidelines state that GLP1RAs cannot currently be recommended as MASH-targeted therapies due to the lack of robust demonstration of histological efficacy on steatohepatitis and liver fibrosis in large phase III trials 1. However, they can be used for their approved indications, and their use improves cardiometabolic outcomes, which is beneficial for patients with MAFLD.

The medication works as a GLP-1 receptor agonist, which helps improve insulin sensitivity, reduce appetite, and promote weight loss—all factors that can positively impact liver health in MAFLD patients. Some key points to consider when using Rybelsus in patients with MAFLD include:

  • Starting with a standard oral dose of 3 mg once daily for 30 days, then increasing to 7 mg once daily, with a possible further increase to 14 mg daily if needed for glycemic control
  • Taking the medication at least 30 minutes before the first food, beverage, or other oral medications of the day, with no more than 4 ounces of plain water
  • Monitoring patients for gastrointestinal side effects, which are common with GLP-1 receptor agonists
  • Using the medication with caution in those with a history of pancreatitis or severe gastrointestinal disease

Overall, Rybelsus can be a valuable treatment option for patients with MAFLD, particularly those with concurrent type 2 diabetes, obesity, or insulin resistance, as it can help improve glycemic control, promote weight loss, and reduce the risk of cardiovascular complications 1.

From the Research

Rybelsus (Semaglutide) and MAFLD

  • Rybelsus (semaglutide) is not contraindicated in MAFLD (Metabolic Associated Fatty Liver Disease) 2, 3, 4.
  • In fact, studies suggest that semaglutide may have a beneficial effect on liver steatosis and fibrosis in patients with MAFLD 3, 4.
  • A meta-analysis found that semaglutide improved alanine aminotransferase (ALT) levels, liver stiffness, and steatosis in patients with MAFLD 4.
  • Another study found that semaglutide reduced the hepatic steatosis index (HSI) and fibrosis-4 (FIB-4) index in patients with type 2 diabetes and MAFLD 3.

Comparison with Other Treatments

  • Sodium-glucose cotransporter 2 (SGLT-2) inhibitors, such as canagliflozin, have also been shown to improve liver-related outcomes in patients with MAFLD 5.
  • A study found that SGLT-2 inhibitors and pioglitazone improved liver enzymes, but SGLT-2 inhibitors had a larger improvement in FIB-4 index than pioglitazone in patients with MAFLD 6.
  • However, more research is needed to compare the efficacy of semaglutide with other treatments for MAFLD.

Safety and Efficacy

  • Semaglutide has been shown to be safe and effective in improving glycemic control and weight loss in patients with type 2 diabetes 2, 3, 4.
  • However, semaglutide may increase the risk of adverse events such as diarrhea, nausea, and vomiting 4.
  • Further studies are needed to fully understand the safety and efficacy of semaglutide in patients with MAFLD.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.