Who should not take Rybelsus: warnings, interactions and pregnancy

In the US, Rybelsus must not be used by people with a personal or family history of medullary thyroid carcinoma (MTC), people with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), or anyone who has had a serious allergic reaction to semaglutide or any of the tablet's ingredients¹. In the EU and UK, the only formal contraindication is allergy to the medicine²³. Several other situations need caution or a conversation with your prescriber first: a history of pancreatitis, diabetic eye disease, use with insulin or a sulfonylurea, pregnancy or plans for one (the labels say to stop at least 2 months before a planned pregnancy), breastfeeding, planned surgery, and taking levothyroxine or other daily tablets¹²⁴.

This guide summarises the official prescribing information. It does not replace advice from your doctor or pharmacist, who know your full medical history. In the US, the newer 1.5, 4 and 9 mg tablets are sold as Ozempic tablets and carry the same warnings¹.

The US boxed warning and who must not take Rybelsus

The US label opens with a boxed warning, printed in a box at the top of the prescribing information. It concerns thyroid C-cell tumours: semaglutide caused these tumours in mice and rats, and it is not known whether it causes them in humans, including MTC, a type of thyroid cancer¹. The US label says Rybelsus must not be used if you have:

• a personal or family history of MTC;
• MEN 2, an inherited condition that causes tumours in hormone-producing glands;
• had a serious allergic reaction to semaglutide or any other ingredient¹.

It also asks people taking it to report a lump or swelling in the neck, hoarseness, trouble swallowing or shortness of breath¹.

The EU and UK labels have no boxed warning. Their only contraindication is hypersensitivity (allergy) to semaglutide or an ingredient, and the rodent thyroid finding is described in the section on animal studies²³. Rybelsus is licensed for adults only¹², and the UK label says it should not be used in type 1 diabetes or to treat diabetic ketoacidosis, a dangerous build-up of acids in the blood².

Conditions that need extra care

A history of pancreatitis

Semaglutide has not been studied in people who have had pancreatitis (inflammation of the pancreas), so it should be used with caution. If pancreatitis is suspected the medicine should be stopped, and the UK label says it should not be restarted if pancreatitis is confirmed¹². In the SOUL trial, confirmed acute pancreatitis occurred in 0.4% of people on oral semaglutide and 0.4% on placebo³.

Diabetic retinopathy

Diabetic retinopathy is damage to the blood vessels at the back of the eye. A rapid improvement in blood sugar can temporarily make it worse, so people with a history of it should be monitored¹². In the SUSTAIN-6 trial of injected semaglutide, the increase in eye complications was larger in people who already had retinopathy (8.2% vs 5.2%) than in those who did not (0.7% vs 0.4%)¹.

Kidney and liver problems

No dose change is needed for kidney or liver impairment, although experience in end-stage kidney disease and severe liver impairment is limited¹². The main kidney risk is dehydration: acute kidney injury, sometimes needing dialysis, has been reported mostly in people who lost fluids through nausea, vomiting or diarrhoea, and kidney function should be monitored in people with these symptoms¹.

Gallbladder disease

Gallstones and gallbladder inflammation (cholecystitis) have been reported, and gallbladder tests are indicated if they are suspected¹.

Stomach, heart and other conditions

Rybelsus is not recommended in severe gastroparesis, a condition in which the stomach empties very slowly¹². The UK label also says it is not recommended in the most severe heart failure (NYHA class IV), where there is no experience, and that there is no experience in people who have had bariatric (weight-loss) surgery².

Low blood sugar with insulin or sulfonylureas

Semaglutide boosts insulin release only when blood sugar is raised, so used without other medicines that cause hypoglycaemia (low blood sugar), the risk is low¹. The risk rises, including the risk of severe hypoglycaemia, when it is combined with insulin or an insulin secretagogue such as a sulfonylurea. When Rybelsus is started alongside these medicines, the prescriber may reduce their dose¹².

Dizziness can happen, mainly while the dose is being increased, and hypoglycaemia can affect your ability to drive. The NHS advises not driving if you feel dizzy or have problems with your vision²⁴.

Pregnancy, contraception and breastfeeding

The labels say semaglutide should be stopped at least 2 months before a planned pregnancy, because it takes a long time to leave the body¹²⁴. Its half-life is about one week, and it stays in the blood for about five weeks after the last dose¹. If you are planning a pregnancy, talk to your prescriber about your diabetes treatment well in advance.

• Pregnancy: the UK label says semaglutide should not be used during pregnancy². The US label says it should be used in pregnancy only if the potential benefit justifies the potential risk to the baby, because animal studies showed harm, and the tablet's absorption enhancer, SNAC, crosses the placenta in rats¹.
• Contraception: the UK label says women who could become pregnant must use effective contraception², and the MHRA repeated this in its June 2025 advice on GLP-1 medicines⁵⁶. Semaglutide tablets did not change blood levels of the oral contraceptive hormones ethinylestradiol and levonorgestrel. That differs from tirzepatide (Mounjaro), for which the MHRA advises adding a barrier method for 4 weeks after starting and after each dose increase¹²⁶.
• Breastfeeding: not recommended in the US, and should not be used in the UK and EU. In a lactation study, semaglutide was below measurable levels in breast milk, but SNAC and its breakdown products were present, and babies may clear SNAC more slowly¹².

Surgery, anaesthesia and sedation

Semaglutide slows how fast your stomach empties. There have been rare reports of pulmonary aspiration, when stomach contents get into the lungs, in people taking GLP-1 medicines who had a general anaesthetic or deep sedation, even though they had followed fasting instructions¹⁷.

The US label says there is not enough data to recommend changes to fasting or stopping the medicine beforehand, and asks patients to tell their healthcare providers before any planned surgery or procedure¹. The UK label asks clinicians to consider the increased risk of food remaining in the stomach before procedures under general anaesthesia or deep sedation². In practice, tell the team doing your procedure that you take Rybelsus, and follow their instructions.

Rybelsus interactions with other medicines

Most interactions come from two things: the 30-minute rule, and the fact that semaglutide slows stomach emptying, which can change how other tablets are absorbed¹.

The 30-minute rule

Rybelsus is taken on an empty stomach, and other oral medicines must wait until at least 30 minutes after the dose¹². Taking it together with other tablets reduces how much semaglutide is absorbed: in an EU study, taking it with five other tablets reduced semaglutide exposure by 34%³. For medicines where small changes in blood levels matter (a narrow therapeutic index) or that need clinical monitoring, the US label advises extra monitoring¹. See how to take Rybelsus for the full routine.

Rybelsus and levothyroxine

Levothyroxine (thyroid hormone replacement) needs particular care, because both medicines are usually taken on waking. When levothyroxine was taken together with semaglutide tablets, total exposure to thyroxine rose by 33%, and the labels advise considering thyroid monitoring¹². If you take both, ask your prescriber or pharmacist how to time them and whether your thyroid levels should be checked.

Other medicines

The NHS also advises avoiding alcohol, because it can make nausea and vomiting worse⁴.

What to tell your prescriber before you start

• Any personal or family history of thyroid cancer (MTC) or MEN 2.
• Past pancreatitis, gallbladder problems or severe gastroparesis.
• Diabetic eye disease, and any recent change in your vision.
• Kidney problems, or a tendency to become dehydrated.
• Every medicine you take, especially insulin, sulfonylureas, levothyroxine, warfarin or acenocoumarol, and any other GLP-1 medicine.
• Whether you are pregnant, planning a pregnancy or breastfeeding, and what contraception you use.
• Any planned surgery or procedure under general anaesthesia or deep sedation.

For day-to-day effects such as nausea, see Rybelsus side effects.