What are the contraindications for Rybelsus (semaglutide) in patients with diabetes?

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Last updated: June 23, 2025View editorial policy

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From the Guidelines

Rybelsus (oral semaglutide) is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). It should not be used in patients with a history of serious hypersensitivity reactions to semaglutide or any of the product components. Rybelsus is also contraindicated during pregnancy as weight loss and reduced caloric intake may harm fetal development. Patients with type 1 diabetes should not use Rybelsus as it is only approved for type 2 diabetes. Caution is needed in patients with severe gastrointestinal disease, including gastroparesis, as Rybelsus may worsen these conditions. The medication should be used carefully in patients with a history of pancreatitis or with risk factors for pancreatitis. Patients with severe renal impairment (eGFR less than 30 mL/min/1.73 m²) should use Rybelsus with caution due to limited experience in this population. These contraindications exist because semaglutide, as a GLP-1 receptor agonist, has been associated with thyroid C-cell tumors in rodent studies, can cause significant gastrointestinal side effects, and may affect kidney function in susceptible individuals, as noted in studies such as 1 and 1.

Some key points to consider when prescribing Rybelsus include:

  • Contraindications: personal or family history of MTC or MEN 2, serious hypersensitivity reactions to semaglutide, pregnancy
  • Caution in patients with: severe gastrointestinal disease, history of pancreatitis, severe renal impairment
  • Monitoring for: gastrointestinal side effects, pancreatitis, kidney function
  • Benefits: improved glycemic control, weight loss, potential cardiovascular benefits, as seen in studies such as 1, 1, and 1
  • Potential risks: thyroid C-cell tumors, gastrointestinal side effects, kidney function impairment, as noted in studies such as 1.

Overall, Rybelsus can be a useful treatment option for patients with type 2 diabetes, but it is essential to carefully consider the potential benefits and risks and to monitor patients closely for any adverse effects, as recommended in guidelines such as those outlined in 1 and 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Rybelsus Contraindications in Diabetes

The contraindications for Rybelsus (semaglutide) in patients with diabetes include:

  • Personal or family history of medullary thyroid carcinoma 2, 3
  • Multiple endocrine neoplasia syndrome type 2 2, 3
  • History of pancreatitis, as semaglutide is not recommended in patients with suspected or confirmed pancreatitis 2
  • Type 1 diabetes, as semaglutide is not indicated for this condition 2
  • Pregnancy, as semaglutide is contraindicated in pregnant women 3

Warnings and Precautions

In addition to the contraindications, there are several warnings and precautions to consider when using Rybelsus:

  • Risk of thyroid C-cell tumors, as semaglutide has been associated with an increased risk of these tumors 3, 4
  • Risk of pancreatitis, as semaglutide has been associated with an increased risk of pancreatitis 3, 4
  • Risk of acute kidney injury, as semaglutide has been associated with an increased risk of acute kidney injury 3, 4
  • Risk of diabetic retinopathy, as semaglutide has been associated with an increased risk of diabetic retinopathy complications 4

Administration Instructions

To minimize the risk of gastrointestinal adverse events, patients should:

  • Swallow the tablet with up to 4 fl oz/120 mL of water on an empty stomach upon waking 2
  • Wait at least 30 minutes before eating, drinking, or taking other oral medications 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Semaglutide: Double-edged Sword with Risks and Benefits.

Archives of internal medicine research, 2025

Research

Safety of Semaglutide.

Frontiers in endocrinology, 2021

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.

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