Rybelsus side effects: what the Canadian product monograph says

Most common side effects

The most frequently reported adverse reactions in clinical trials were gastrointestinal disorders, including nausea, diarrhea and vomiting. In general, these reactions were mild or moderate in severity and of short duration.

The majority of the reports of nausea, vomiting and/or diarrhea occurred during dose escalation.

In placebo-controlled trials, gastrointestinal adverse reactions occurred in 31.8% of patients on 7 mg, 41.0% on 14 mg and 21.3% on placebo.

The product monograph gives these frequencies from two placebo-controlled trials. The three numbers are for Rybelsus 7 mg, Rybelsus 14 mg and placebo.

• Nausea: 11.0%, 19.7% and 6.4%.
• Abdominal pain: 10.1%, 10.7% and 4.1%.
• Diarrhea: 8.7%, 10.1% and 4.1%.
• Vomiting: 6.2%, 8.4% and 3.0%.
• Decreased appetite: 5.9%, 9.0% and 0.8%.
• Constipation: 5.9%, 5.3% and 2.5%.

Frequency words in the patient information

The patient information of the product monograph groups the side effects by frequency. It says that nausea and diarrhea usually go away over time.

• Very common (may affect more than 1 in 10 people): nausea, diarrhea, and low blood sugar when this medicine is used with insulin or sulfonylureas.
• Common (may affect up to 1 in 10 people): vomiting, upset stomach or indigestion, gastritis, reflux or heartburn, stomach pain, bloating of the stomach, constipation.
• Also common: a change in the way food or drink tastes, tiredness, less appetite, gas, increase of pancreatic enzymes, feeling dizzy, headache, changed skin sensation.
• Uncommon (may affect up to 1 in 100 people): weight loss, gallstones, burping, fast pulse.
• Also uncommon: allergic reactions like rash, itching or hives, a delay in the emptying of the stomach.
• Rare (may affect up to 1 in 1,000 people): serious allergic reactions (anaphylactic reactions).
• Unknown: intestinal obstruction, including ileus.

Serious warnings and precautions box

The product monograph has a serious warnings and precautions box. Its title is: Risk of Thyroid C-cell Tumours.

Semaglutide causes thyroid C-cell tumours in rats and mice at clinically relevant exposures. It is unknown whether semaglutide causes thyroid C-cell tumours, including medullary thyroid carcinoma (MTC), in humans. The box says that patients should be counseled regarding the risk and symptoms of thyroid tumours.

The product monograph also lists these serious adverse reactions:

• Pancreatitis.
• Diabetic retinopathy.
• Hypoglycemia with concomitant use of insulin or sulfonylureas.
• Renal insufficiency.
• Hypersensitivity.
• Ileus.

Who must not use Rybelsus

Rybelsus is contraindicated in patients who are hypersensitive to Rybelsus, to any ingredient in the formulation or to a component of the container.

Rybelsus is contraindicated in patients who have a personal or family history of medullary thyroid carcinoma (MTC). It is also contraindicated in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

Rybelsus should not be used during pregnancy or breastfeeding. The product monograph says that Rybelsus should be discontinued at least 2 months before a planned pregnancy.

The product monograph also says:

• Rybelsus should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
• Semaglutide is not recommended in patients with severe gastroparesis.
• Semaglutide is not recommended in patients with congestive heart failure New York Heart Association (NYHA) class IV.
• Rybelsus is not indicated for use in pediatric patients (under 18 years of age).

When to stop and get medical help

The patient information has a table of serious side effects.

For three side effects, the table says to talk to your healthcare professional in all cases. These are diabetic retinopathy complications, gallbladder disease symptoms and severe hypoglycemia (low blood sugar).

If you have severe and on-going pain in the stomach area or jaundice, see a doctor straight away. The patient information says that this could be a sign of acute pancreatitis or gallbladder disease.

If you notice a sudden loss of vision or rapidly worsening eyesight, urgently contact your doctor. If a hypersensitivity reaction occurs, the patient should discontinue Rybelsus and promptly seek medical advice.

For these side effects, the table says to stop taking the drug and get immediate medical help:

• Pancreatitis (uncommon): severe and ongoing pain in the stomach area.
• Severe allergic reaction (rare): breathing problems, swelling of face and throat and a fast heartbeat.
• Non-arteritic anterior ischemic optic neuropathy, NAION (very rare): a sudden loss of vision or rapidly worsening eyesight.

Ask a health professional

This page repeats what the Canadian product monograph says. It is not medical advice. Ask your pharmacist or your prescriber what applies to you.