Rybelsus side effects – what is common and what should you look out for?

What is Rybelsus and how does it work?

Rybelsus is a prescription medication containing the active substance semaglutid. It belongs to the drug class of GLP-1 receptor agonists, which mimic the effect of the body's own hormone, glucagon-like peptide-1 (GLP-1). This hormone is involved in the regulation of blood sugar, appetite, and satiety. Unlike other semaglutide preparations, such as Wegovy and Ozempic which are administered as subcutaneous injections, Rybelsus is taken as a daily tablet.

Rybelsus is available in strengths of 3 mg, 7 mg, and 14 mg. The medication is approved for the treatment of individuals with type 2 diabetes as an adjunct to diet and physical activity.

Semaglutide also has an appetite-regulating effect that can contribute to weight loss. However, Rybelsus is not approved for the treatment of obesity. In certain cases, a doctor may, after an individual medical assessment, choose to prescribe the medication outside of its approved indication (so-called off-label use).

Rybelsus is a medication developed by Novo Nordisk indicated for the treatment of insufficiently controlled type 2 diabetes as a supplement to diet and physical activity.

Common side effects of Rybelsus

Because Rybelsus affects the digestive system, the vast majority of side effects are gastrointestinal – meaning they are linked to the stomach and intestinal tract.

These are the most common side effects:

• Nausea: Nausea is the most common side effect but usually passes over time. It most often occurs because food remains in the stomach longer than the body is used to.

• Diarrhea: Can occur as bowel movements change during the first few weeks.

• Constipation: When eating smaller amounts of food and bowel movements become slower, more fluid has time to be absorbed by the body, which can make the stool hard.

• Heartburn and gastritis: Usually occurs because the stomach empties more slowly, increasing the risk of stomach contents being pushed up into the esophagus.

• Gas and bloating: Often occurs as a result of delayed digestion.

These issues are generally mild to moderate. They most often appear right when you start using the tablet or during periods when the dose is being titrated up to the next level.

Read more about the most common side effects during treatment with GLP-1 medications.

How long do the side effects last?

It is important to know that for the vast majority, the side effects are temporary. They are most prominent during the first weeks of treatment. As your body adapts to the slower gastric emptying and the new hormone levels, the issues will usually decrease significantly and, for many, disappear completely.

Working with a gradual dose titration of the medication – starting at a low dose and then increasing it step-by-step – is the most important tool in healthcare to give the body time to adjust and thereby keep side effects to a minimum.

Less common but more serious side effects

Rybelsus is a well-studied medication and is generally considered safe when used according to the approved indication and under medical supervision. As with all drug treatments, however, there are rarer but potentially serious side effects that require medical assessment:

• Hypoglycemia (low blood sugar): During treatment with Rybelsus as monotherapy, the risk of clinically significant hypoglycemia is low. The risk increases with concurrent treatment with insulin or sulfonylureas, and doses may need to be adjusted by a doctor.

• Pancreatitis (inflammation of the pancreas): A very rare risk. Severe and persistent abdominal pain may indicate acute pancreatitis and requires immediate medical assessment. Rybelsus should be used with caution in patients who have previously had pancreatitis.

• Gallstone issues: During rapid and significant weight loss – regardless of method – the risk of developing gallstones increases.

• Increased heart rate: A certain increase in pulse may occur during treatment with semaglutide.

• Serious allergic reactions: Symptoms such as difficulty breathing, swelling of the face or throat, or generalized rash require immediate medical assessment. The medication should not be used in cases of known hypersensitivity to semaglutide or any excipient.

Other things to consider:

• Combination with other medications: Always inform your doctor or pharmacist if you are taking other medications along with Rybelsus, as this can affect the safety and effectiveness of the treatment.

• Surgery: Inform your doctor if you are going to undergo surgery with general anesthesia.

• Pregnancy or breastfeeding: Rybelsus is not recommended during pregnancy or breastfeeding. Women of childbearing age should use effective contraception during treatment. Treatment should be discontinued at least two months before a planned pregnancy.

For questions about side effects or if you need more advice, always contact your healthcare provider.

Can you reduce the risk of potential side effects?

Yes, there are several measures that can help reduce and prevent stomach issues during treatment with Rybelsus.

Gradual dose titration is a central strategy to improve tolerance. By using the lowest effective dose and only increasing the dose when necessary, the body gets time to adapt, which can reduce the risk of side effects.

Adjustments to eating habits can also help:

• Eat smaller portions: Since gastric emptying is delayed, large meals can increase the risk of nausea and discomfort. Smaller portions and avoiding eating until overfull can improve tolerance.

• Eat slowly: It takes up to 20 minutes for the brain to register satiety. Chew well and put down your cutlery between bites.

• Avoid fatty and fried food: Fatty food, strong spices, and heavy sauces stay in the stomach even longer and often worsen bloating and heartburn.

• Drink plenty of water: A regular fluid intake reduces the risk of constipation.

When should you contact a doctor?

Although most side effects can be managed with diet, adjustments, and patience, there are situations where medical assessment is necessary. You should always contact your healthcare team or seek medical care if you experience:

• Severe, persistent abdominal pain (especially if the pain radiates toward the back), which can be a sign of pancreatitis or gallstones – contact a doctor immediately.

• Vomiting or diarrhea that is so severe that you cannot keep fluids down and risk dehydration – seek care immediately.

• Signs of a serious allergic reaction, such as difficulty breathing, swelling of the face, lips, tongue, or throat, or a severe skin rash. Seek emergency care for such symptoms.

• If side effects do not subside and affect your everyday life to a large extent.

Remember that Rybelsus should be taken once daily as a tablet for the best effect. It is important to follow the doctor's instructions for the best absorption of the medication. If you miss a dose, you should skip it and take the next dose as usual the following day. You should not take a double dose to compensate.

Frequently asked questions about Rybelsus side effects

Is Rybelsus safe to use?

When Rybelsus is prescribed and monitored by a doctor, it is generally considered safe for the correct patient group. Before treatment begins, an individual medical assessment is performed to ensure that the medication is suitable based on your health profile and any risk factors.

Are the side effects permanent?

No, most side effects are temporary. Common gastrointestinal issues like nausea, diarrhea, or constipation appear primarily at the start of treatment or during dose increases and often decrease as the body adapts.

Is Rybelsus the same thing as Ozempic?

Rybelsus and Ozempic contain the same active substance, semaglutide, and have the same mechanism of action as GLP-1 receptor agonists. The difference is that Rybelsus is taken as a daily tablet, while Ozempic is given as an injection once per week. The form of administration, dosage, and absorption in the body differ, but the biological effect is essentially the same.

Sources

EMA: Rybelsus – EPAR Product Information.
https://www.ema.europa.eu/en/medicines/human/EPAR/rybelsus

The Lancet. Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS-1): a randomised, double-blind, placebo-controlled, phase 3 trial. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01185-6/fulltext

Journal of Clinical Medicine. Clinical Recommendations to Manage Gastrointestinal Adverse Events in Patients Treated with Glp-1 Receptor Agonists: A Multidisciplinary Expert Consensus.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9821052/

The New England Journal of Medicine. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1).
https://www.nejm.org/doi/full/10.1056/NEJMoa2032183