Rybelsus: 7 things you should know

Medically reviewed by Carmen Fookes, BPharm. Last updated on March 1, 2023.

1. How it works

• Rybelsus is a brand (trade) name for semaglutide which may be used to treat type 2 diabetes in adults.
• Rybelsus works by mimicking the functions of natural incretin hormones in the body that help keep blood sugar levels under control, especially immediately following a meal. Incretin hormones are gut peptides that are secreted from the stomach when food is eaten. They also stimulate the secretion of insulin in response to high blood glucose levels. Two incretin hormones are known as GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1).
• In people with type 2 diabetes, natural incretin release is diminished or no longer present. However, it can be stimulated with pharmacological agents, such as Rybelsus. Rybelsus (semaglutide) shares 94% of the same structure as human GLP-1 but is man-made. It binds to and activates the GLP-1 receptor, stimulating insulin secretion and lowering glucagon secretion when blood glucose levels are high. It also causes a slowing down in how fast the stomach empties, making a person feel full.
• Rybelsus belongs to the class of medicines called GLP-1 receptor agonists. It may also be called an incretin mimetic.

2. Upsides

• Rybelsus may be used for the treatment of type 2 diabetes in adults over the age of 18 alongside diet modification and increased exercise. It can be prescribed as initial therapy for those who have not previously taken diabetes medication.
• Rybelsus is an oral tablet which is taken once a day. The usual starting dose is 3mg once daily that is given for 30 days. This is then increased to 7mg once a day for 30 days, then further increased to 14mg once a day if needed.
• Rybelsus tablets are formulated with salcaprozoate, which is an absorption promoter. Semaglutide is a large molecule and it is not absorbed through the intestine. The addition of salcaprozoate allows semaglutide to be absorbed which means Rybelsus tablets can be taken orally.
• People treated with Rybelsus 14mg once a day can be transferred to Ozempic subcutaneous injection 0.5 mg once weekly. Those transitioning can start Ozempic the day after their last dose of Rybelsus.
• Weight losses of 2kg to 4kg may occur in people taking Rybelsus for type 2 diabetes. Research has shown that after 26 weeks people lost an average of 5 pounds (2.3kg) while taking Rybelsus 7mg, and 8.1 pounds (3.7kg) while taking Rybelsus 14mg. People with higher initial body weight and those experiencing more digestive symptoms may be more likely to lose weight once treatment with Rybelsus has started. One of the ways Rybelsus works is by helping to make you feel full after a meal.
• No dosage adjustment of Rybelsus is needed in people with kidney or liver disease.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Common side effects of Rybelsus include hypoglycemia (low blood sugar levels), nausea, abdominal pain, diarrhea, decreased appetite, vomiting, and constipation. The risk of hypoglycemia is increased when Rybelsus is used in combination with insulin or sulfonylureas. Small changes in the heartbeat of 2 to 3 beats per minute have also been reported.
• Rybelsus needs to be taken on an empty stomach, otherwise, its absorption is significantly affected.
• Rybelsus is not indicated for use in patients with type 1 diabetes mellitus or the treatment of patients with diabetic ketoacidosis, as it would not be effective in these settings.
• Animal studies have reported thyroid C-cell tumors in rats given semaglutide. It is not known if Rybelsus increases the risk in humans of these tumors.
• Rybelsus has not been studied in people with a history of pancreatitis. Other medications should be tried instead. Rybelsus may increase the risk of pancreatitis. If this occurs, Rybelsus should be discontinued and not restarted. There have also been reports of kidney damage, which may require hemodialysis, in people treated with GLP-1 receptor agonists (RA), such as Rybelsus. Anaphylaxis and angioedema have also been reported with GLP-1 RAs such as Rybelsus.
• Rybelsus should not be used in people with a history of thyroid cancer or those with Multiple Endocrine Neoplasia syndrome type 2.
• Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy and research has shown 4.2% of people reported diabetic retinopathy-related adverse reactions during clinical trials. The risk was greatest for those with previous diabetic retinopathy.
• Rybelsus may increase levels of amylase by 10% to 13% and lipase by 30% to 34% depending on the dosage.
• A small percentage of people receiving Rybelsus may develop antibodies to it. The neutralizing effect of these antibodies is not known.
• Rybelsus has not been adequately studied in pregnant women and should not be used unless the perceived benefits outweigh the risks of uncontrolled diabetes, which include preeclampsia, spontaneous abortions, and preterm delivery.
• There is no generic version of Rybelsus available.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

• Rybelsus (semaglutide) is an oral medicine that can be used as a first-line medication to improve blood sugar control in adults over the age of 18 with type 2 diabetes. It works by mimicking the effects of GLP-1, a naturally occurring hormone that stimulates insulin secretion and lowers glucagon secretion from the liver. People stabilized on Rybelsus tablets can be transferred to Ozempic subcutaneous injection.

5. Tips

• Rybelsus is best taken on an empty stomach when you first wake up, at least 30 minutes before food, and with a small amount of water (no more than 4 oz). This ensures Rybelsus is absorbed properly. After 30 minutes of taking the Rybelsus tablet, you may eat, drink or take other oral medicines.
• Rybelsus tablets need to be swallowed whole. Do not split, crush, or chew tablets.
• Rybelsus needs to be started slowly at 3mg once a day. Starting at a lower dosage helps your body get used to taking the medicine and reduces the risk of digestive side effects, such as nausea, belly pain, diarrhea, decreased appetite, vomiting, and constipation.
• Be careful not to allow yourself to become dehydrated while taking Rybelsus, particularly if you are experiencing gastrointestinal side effects such as diarrhea or vomiting. Drink plenty of fluids throughout the day.
• This low dose is taken for 30 days and it is not effective at lowering blood sugar. After 30 days of taking Rybelsus 3mg a day, your doctor will increase the dose to 7mg once a day. This dose is usually effective at lowering blood sugar levels and may be increased to 14mg a day after 30 days if well tolerated and further blood sugar lowering is desired. Taking two 7mg tablets to achieve a 14mg dose is not recommended.
• If you miss a dose of Rybelsus, administer it as soon as possible, but do not double up the dose. If it is the next day, skip the missed dose and just go back to your normal dosing schedule.
• Report any symptoms of a possible thyroid tumor (such as a lump in the neck, shortness of breath, difficulty swallowing, or persistent hoarseness) to your doctor immediately. Do not take Rybelsus if you or someone in your family has thyroid cancer.
• If you develop persistent, severe, abdominal pain, which may radiate to the back or be accompanied by vomiting, ring your doctor immediately as Rybelsus can increase your risk of developing pancreatitis.
• Rybelsus may temporarily worsen diabetic retinopathy, an eye condition. Tell your doctor if you notice any change in your vision. If you are a woman, use adequate contraception to ensure you do not become pregnant while taking Rybelsus. For a planned pregnancy, it is recommended Rybelsus be discontinued at least two months before conception. Tell your doctor if you inadvertently become pregnant while taking Rybelsus. Do not breastfeed while taking Rybelsus.

6. Response and effectiveness

• Rybelsus is started at a lower than effective dose to reduce the risk of side effects which means benefits will not be seen until the dose is increased to 7mg. The dose is increased from 3mg to 7mg after 30 days so you can expect Rybelsus to start showing an effect from day 31 onward.
• Every time the dosage of Rybelsus is increased it takes 4 to 5 weeks for steady levels to be reached so it may take two to three months before the full effects of Rybelsus are seen. Some people may require 14mg of Rybelsus for it to be effective.
• Rybelsus tablets are formulated with salcaprozoate, which is an absorption promoter. Salcaprozoate helps poorly soluble large molecules, such as semaglutide (but also others such as insulin or heparin), to be absorbed, offering a more convenient way for medications to be taken that are typically given by injection.
• The absorption of Rybelsus primarily occurs in the stomach, but only up to 1% of a dose is absorbed, which is why it is important to take it on an empty stomach. After one dose of Rybelsus, maximum concentrations of semaglutide are reached one hour after administration. After 4 to 5 weeks of regular dosing, blood levels of semaglutide have reached a steady state (this means they remain constant in the blood and don’t fluctuate up and down). Rybelsus lasts a long time in the body – about 4 to 5 weeks after the last dose.
• Clinical studies have shown after 26 weeks, 69% of people taking Rybelsus 7mg achieved an HbA1c of < 7% compared to 77% of patients taking Rybelsus 14mg and only 31% of patients taking a placebo (a pretend pill). Fasting plasma glucose levels also decreased by 28mg/dL in people taking Rybelsus 7mg, by 33mg/dL in people taking Rybelsus 14mg, and only 3mg/dL in people taking placebo.

7. Interactions

Medicines that interact with Rybelsus may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Rybelsus. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with Rybelsus include:

• acetazolamide
• anticonvulsants such as phenytoin
• antipsychotics, such as aripiprazole
• bexarotene
• ciprofloxacin or gatifloxacin
• corticosteroids, such as prednisone or cortisone
• diuretics, such as bumetanide, HCTZ, and bendroflumethiazide
• HIV medications, such as amprenavir, atazanavir, and fosamprenavir
• hormones, such as ethinylestradiol and hydroxyprogesterone
• insulin (may increase the risk of hypoglycemia)
• isoniazid
• other medications that affect blood sugar levels or are used for diabetes, such as glimepiride or metformin (may increase the risk of hypoglycemia).

Alcohol may affect blood glucose levels in people with diabetes, increasing the risk of hypoglycemia. This effect may be compounded by Rybelsus.

Note that this list is not all-inclusive and includes only common medications that may interact with Rybelsus. You should refer to the prescribing information for Rybelsus for a complete list of interactions.

Also, because Rybelsus causes a delay in gastric emptying, it may impact the absorption of any medication taken orally. However, in clinical trials, this did not appear to change the effects of other medications.

References

• Rybelsus (semaglutide) [Package insert]. Updated 12/2022. Novo Nordisk. https://www.drugs.com/pro/rybelsus.html
• Novo Nordisk Announces FDA Approval of Label Update for Rybelsus (semaglutide) Allowing Use as a First-Line Option for Adults with Type 2 Diabetes Updated Jan 12, 2023. https://www.drugs.com/newdrugs/novo-nordisk-announces-fda-approval-label-update-rybelsus-semaglutide-allowing-first-line-option-5957.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Rybelsus only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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