Rybelsus (semaglutide) is an oral GLP-1 receptor agonist licensed in the UK for treating type 2 diabetes in adults. Concerns about whether Rybelsus causes cancer have arisen primarily from animal studies showing thyroid C-cell tumours in rodents. However, current evidence does not establish a causal link between semaglutide and cancer in humans. UK regulatory bodies, including the MHRA, continue to monitor safety data closely. This article examines the evidence, regulatory guidance, and what patients should discuss with their GP before starting treatment.

What Is Rybelsus and How Does It Work?

Rybelsus (semaglutide) is an oral medication licensed in the UK for the treatment of type 2 diabetes mellitus in adults. It is used as an adjunct to diet and exercise, either as monotherapy when metformin is inappropriate, or as add-on therapy. It belongs to a class of drugs known as glucagon-like peptide-1 (GLP-1) receptor agonists. Rybelsus is the first GLP-1 receptor agonist available in tablet form, offering an alternative to injectable formulations such as Ozempic (also semaglutide) and other similar agents.

The mechanism of action centres on mimicking the naturally occurring hormone GLP-1, which is released by the intestine in response to food intake. Semaglutide works by:

• Stimulating insulin secretion from pancreatic beta cells in a glucose-dependent manner, which helps lower blood sugar levels when they are elevated

• Suppressing glucagon release, thereby reducing hepatic glucose production

• Slowing gastric emptying, which moderates the rate at which glucose enters the bloodstream after meals

• Reducing appetite through central nervous system effects, which may contribute to weight loss

Rybelsus is typically initiated at 3 mg once daily (an initiation dose only, not for long-term glycaemic control). After at least 30 days, the dose is increased to 7 mg once daily, and may be further increased to 14 mg once daily after at least another 30 days if needed for glycaemic control.

The medication must be taken in the morning on an empty stomach with up to 120 mL of water. The tablet should be swallowed whole (not split, crushed or chewed) and you must wait at least 30 minutes before consuming food, drink, or other oral medications to ensure adequate absorption.

Common adverse effects include gastrointestinal symptoms such as nausea, vomiting, diarrhoea, and abdominal discomfort, which often diminish over time. When used with insulin or sulfonylureas, there is an increased risk of hypoglycaemia, and dose reductions of these medications may be needed.

If you miss a dose, skip the missed dose and take your next dose the following day as usual. Do not take an extra dose to make up for the missed one.

Thyroid Cancer Warnings and Risk Factors

Concerns about a potential link between GLP-1 receptor agonists and thyroid cancer stem primarily from preclinical animal studies. In rodent models, semaglutide and other drugs in this class have been associated with an increased incidence of thyroid C-cell tumours (medullary thyroid carcinoma, or MTC). These findings led to the inclusion of prominent safety warnings in UK product literature.

It is important to understand that there is no established causal link between semaglutide and thyroid cancer in humans, though a risk cannot be completely excluded. The rodent studies involved doses and exposure durations far exceeding those used in clinical practice, and rodents have a much higher density of GLP-1 receptors in thyroid C-cells compared to humans. Current clinical trial data and post-marketing surveillance have not demonstrated an increased risk of medullary thyroid carcinoma in patients taking semaglutide.

Nevertheless, as a precautionary measure, UK prescribing information advises caution in patients with:

• A personal history of medullary thyroid carcinoma (MTC)

• Multiple endocrine neoplasia syndrome type 2 (MEN 2), a rare inherited condition associated with increased MTC risk

• A family history of MTC or MEN 2

Patients should be counselled to report symptoms that could suggest thyroid tumours, such as a persistent lump or swelling in the neck, difficulty swallowing, persistent hoarseness, or shortness of breath. If any of these symptoms develop, urgent assessment by a GP and potential referral to an endocrinologist or ear, nose, and throat (ENT) specialist is warranted. Routine thyroid monitoring (such as calcitonin testing) is not currently recommended for all patients on Rybelsus, but individual risk assessment should guide clinical decision-making.

MHRA and Regulatory Safety Information

The Medicines and Healthcare products Regulatory Agency (MHRA) in the UK, alongside the European Medicines Agency (EMA), continuously monitors the safety profile of semaglutide and other GLP-1 receptor agonists through pharmacovigilance programmes. Rybelsus received marketing authorisation in the UK following rigorous evaluation of clinical trial data demonstrating efficacy in glycaemic control and an acceptable safety profile.

Regulatory bodies have acknowledged the theoretical thyroid cancer risk based on animal data but emphasise that overall human data do not show an increased incidence of medullary thyroid carcinoma or other thyroid malignancies in patients treated with semaglutide, though a small risk cannot be excluded. The MHRA and EMA require that product information clearly states the warnings related to thyroid safety, ensuring prescribers and patients are appropriately informed.

In addition to thyroid safety, the MHRA has issued guidance on other important safety considerations for GLP-1 receptor agonists, including:

• Acute pancreatitis: Patients should be advised to seek immediate medical attention if they experience severe, persistent abdominal pain

• Diabetic retinopathy complications: Rapid improvement in glycaemic control has been associated with temporary worsening of diabetic retinopathy in some patients

• Renal impairment: Gastrointestinal adverse effects leading to dehydration may affect kidney function

• Gallbladder disease: There is a risk of cholelithiasis (gallstones) and cholecystitis; seek medical review if experiencing right upper quadrant pain, fever, or jaundice

• Hypoglycaemia: Risk increases when used with insulin or sulfonylureas; dose reductions of these medications may be needed

Healthcare professionals are encouraged to report any suspected adverse reactions via the Yellow Card Scheme (yellowcard.mhra.gov.uk or the Yellow Card app), which contributes to ongoing safety surveillance. Patients can also report side effects directly through this system. This post-marketing monitoring is essential for detecting rare or long-term adverse effects that may not have been apparent in clinical trials, thereby ensuring that the benefit-risk profile of Rybelsus remains favourable in real-world use.

What to Discuss With Your GP Before Starting Rybelsus

Before initiating treatment with Rybelsus, a thorough discussion with your GP or diabetes specialist is essential to ensure the medication is appropriate and safe for your individual circumstances. Key topics to address include:

Personal and family medical history: Inform your GP if you have a personal or family history of thyroid cancer (particularly medullary thyroid carcinoma), multiple endocrine neoplasia syndrome type 2, or any other thyroid disorders. While these are not formal contraindications in the UK, they warrant careful consideration and monitoring.

History of pancreatitis: If you have previously experienced pancreatitis (inflammation of the pancreas), discuss this with your doctor. GLP-1 receptor agonists have been associated with pancreatitis, and you should be advised to stop treatment and seek urgent medical attention if severe, persistent abdominal pain occurs.

Kidney function: Patients with moderate to severe renal impairment should be monitored carefully, as gastrointestinal side effects can lead to dehydration and potentially worsen kidney function.

Diabetic retinopathy: If you have pre-existing diabetic eye disease, your GP may recommend closer ophthalmological monitoring, particularly during the initial months of treatment when blood glucose levels are improving rapidly.

Current medications: Rybelsus can affect the absorption of other oral medications due to delayed gastric emptying. Discuss all current medications, including over-the-counter drugs and supplements, to identify potential interactions. Specific monitoring may be needed if you take levothyroxine (monitor thyroid function) or warfarin (monitor INR).

Pregnancy and breastfeeding: Semaglutide is not recommended during pregnancy or breastfeeding. If you are planning pregnancy, you should discontinue Rybelsus at least 2 months before planned conception. Effective contraception is advised during treatment. If you discover you are pregnant, contact your GP immediately to discuss alternative diabetes management strategies.

Risk of hypoglycaemia: If you are also taking insulin or sulfonylureas, there is an increased risk of low blood sugar. Your doctor may need to reduce the doses of these medications when starting Rybelsus.

Gallbladder disease: Be aware of symptoms such as right upper abdominal pain, fever, or yellowing of the skin/eyes, which require prompt medical assessment.

Your GP will also assess whether Rybelsus aligns with NICE guidance for type 2 diabetes management, considering factors such as your HbA1c level, body mass index (BMI), cardiovascular risk, and previous treatment responses. Open communication with your healthcare team ensures that Rybelsus is used safely and effectively as part of your overall diabetes care plan.

Frequently Asked Questions