Rybelsus vs. Ozempic: differences and similarities

If you’re a person with Type 2 diabetes, you know how important it is to maintain healthy blood sugar levels. And you likely rely on some kind of diabetes medication to help you do so. Rybelsus and Ozempic are two brand-name Type 2 diabetes medications your healthcare provider may prescribe if your current drug regimen is not working effectively.

Here’s what you need to know about Rybelsus and Ozempic, including how they’re similar and how they’re different. 

What are Rybelsus and Ozempic?

Rybelsus and Ozempic are both brand names of the same drug, semaglutide. Semaglutide is a type of medication called a glucagon-like peptide-1 receptor agonist (GLP-1 RA) that healthcare providers sometimes prescribe to those with Type 2 diabetes if other medications, like metformin, aren’t effective enough (ADA, 2021).

A GLP-1 RA attaches to a protein called the GLP-1 receptor, which is found in your pancreas, brain, stomach, and intestines. When GLP-1 RA binds at those receptors attached, it makes the pancreas produce more of a hormone called insulin that lowers your blood sugar. It also decreases the amount of sugar (glucose) that your intestines absorb and sends signals to your brain to help you control your appetite. This might lead to weight loss (Shaefer, 2015).

What is Rybelsus?

Rybelsus is an oral form of semaglutide that comes in tablets of 3 mg, 7 mg, and 14 mg. You usually take Rybelsus once a day in the morning, at least 30 minutes before you eat or drink anything (FDA-a, 2019).

The typical starting dose of Rybelsus is 3 mg once a day for 30 days. After the first 30 days, your healthcare provider adjusts your Rybelsus dosage based on how you respond to the treatment and any symptoms or side effects you develop. 

What is Ozempic?

Ozempic (see Important Safety Information) is an injectable form of semaglutide. You usually take an Ozempic injection in your belly or thigh once a week. You can inject the Ozempic dose yourself or ask someone you know to inject it for you (FDA, 2017). 

The typical starting dose of Ozempic is 0.25 mg once a week for four weeks. It’s a good idea to inject it on the same day each week. Depending on side effects and how you respond to the medication, your healthcare provider may slowly increase your dose to a maximum of 1 mg weekly. 

Conditions treated with Rybelsus and Ozempic

Ozempic and Rybelsus are approved by the U.S. Food and Drug Administration (FDA) to treat Type 2 diabetes.  

Rybelsus uses

Rybelsus is FDA-approved for people who have Type 2 diabetes. It lowers blood sugar (glucose) along with a nutritious diet and exercise. During clinical trials, researchers found that people with Type 2 diabetes who took Rybelsus reduced their blood sugar test (Hemoglobin A1C level) significantly more than those who took a placebo (Anderson, 2020; Davies, 2017). 

Ozempic uses

Ozempic is also FDA-approved for people with Type 2 diabetes. Your healthcare provider may prescribe Ozempic for (FDA-b, 2019):

• Lowering your blood sugar: In clinical trials, people with Type 2 diabetes who used Ozempic alone or in combination with other diabetes treatments lowered their blood sugar significantly more than those who took a placebo (Ahrén, 2017; Sorli, 2017). 
• Protecting your heart: People with Type 2 diabetes have a higher risk of heart disease and strokes (cardiovascular diseases). Researchers found that people with Type 2 diabetes who use Ozempic had a 25% lower risk of cardiovascular disease than those who took a placebo (Marso, 2016). 

Some healthcare providers may prescribe Ozempic off-label, meaning that you’re not using it for something the FDA explicitly approved, but it’s the appropriate treatment in the provider’s judgment. For example, it’s sometimes used off-label to help with weight loss. Studies have demonstrated that Ozempic may help control appetite and reduce body fat (Blundell, 2017). Only one brand of semaglutide, an injectable drug called Wegovy (see Important Safety Information), is FDA-approved for weight loss.

Side effects of Rybelsus and Ozempic

Since Rybelsus and Ozempic affect your digestive tract, many of their side effects are related to your stomach and intestines and include nausea and upset stomach, vomiting, decreased appetite, and constipation or diarrhea (FDA, 2017; FDA, 2019-a; FDA, 2019-b).

Severe side effects of Rybelsus and Ozempic are rare but include (FDA, 2017; FDA-a, 2019; FDA-b, 2019):

• Allergic reactions: Rybelsus and Ozempic can cause an allergic reaction in some people. Signs of a medication allergy include chest tightness, difficulty breathing, rashes or hives, and flushing.
• Inflammation of your pancreas (pancreatitis): Pancreatitis is an uncommon but potentially severe side effect of GLP-1 RAs. Signs of pancreatitis include severe abdominal pain, uncontrollable vomiting, and pain in your back. 
• Thyroid cancer: People who take Rybelsus and Ozempic may have a higher risk of a thyroid tumor called medullary thyroid carcinoma. Currently, this side effect was only seen in animal studies, so it’s not clear if the same risk happens in people. 
• Low blood sugar (hypoglycemia): Your blood sugar may get too low when using diabetes medications. It’s not too common with GLP-1 RAs, but it may happen if you combine them with other medications. 
• Kidney problems: GLP-1 RAs may damage your kidneys, especially if you become dehydrated from vomiting. 
• Vision problems: Lowering your blood sugar too quickly may cause blurred vision or a condition called diabetic retinopathy. 

You may have a higher risk of serious side effects from Ozempic and Rybelsus if you have specific underlying medical conditions, so it’s a good idea to let your healthcare provider know if you have or have had any of the following before taking Rybelsus or Ozempic (FDA, 2017; FDA-a, 2019; FDA-b, 2019): 

• Allergic reactions to other medications
• Pancreatitis
• Thyroid cancer, especially medullary thyroid carcinoma (MTC)
• MEN-2 (multiple endocrine neoplasia syndrome type II) 
• A family history of MTC or MEN-2
• Type 1 diabetes
• Diabetic ketoacidosis (a complication of diabetes)
• A current pregnancy or if you’re breastfeeding

Potential drug interactions of Rybelsus and Ozempic

If you’re taking other medications along with Rybelsus or Ozempic, you may have a higher risk of adverse reactions. Medications that may interact with Rybelsus and Ozempic include (FDA, 2017; FDA-a, 2019; FDA-b, 2019): 

• Insulin: Insulin lowers your blood sugar, so your blood sugar may get dangerously low if you combine it with Rybelsus or Ozempic. 
• Metformin: Metformin is a type of drug called a sulfonylurea, which lowers your blood sugar. Your blood sugar level may get too low if you take sulfonylureas with Rybelsus or Ozempic. 

Rybelsus may also interact with a thyroid medication called levothyroxine. When they’re combined, the Rybelsus may become less effective. Rybelsus may also interfere with your body’s ability to get rid of levothyroxine, which increases your risk of side effects (FDA, 2017). 

Differences and similarities between Rybelsus vs. Ozempic

Key similarities and differences between Rybelsus and Ozempic include:

Rybelsus vs. Ozempic efficacy

In clinical trials, both Rybelsus and Ozempic were effective at treating Type 2 diabetes and lowering blood sugar levels (Anderson 2020; Ahrén 2017). There are currently no trials that compare them to each other to determine which one is more effective. 

Rybelsus vs. Ozempic cost

Rybelsus and Ozempic are both brand-name medications that are not available in a generic form. The cost of both medications is similar. According to GoodRx, the average monthly price of Rybelsus is $1,011.72, and the average monthly price of Ozempic is $1,011.54 (GoodRx-a, 2022; GoodRx-b, 2022). 

That said, many insurance companies cover part or all of the medication cost, so it’s a good idea to check with your insurance provider to see what your cost would be. Some pharmacies also offer coupons and discounts to help you pay for your prescription.  

If you have Type 2 diabetes and medications like metformin don’t help control your blood sugar enough, there are other options, including GLP-1 RAs like semaglutide. Your healthcare provider can help you decide whether the oral formulation Rybelsus or the weekly injection Ozempic is the right medicine for you.

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Disclaimer

If you have any medical questions or concerns, please talk to your healthcare provider. The articles on Health Guide are underpinned by peer-reviewed research and information drawn from medical societies and governmental agencies. However, they are not a substitute for professional medical advice, diagnosis, or treatment.

References

1. Ahrén, B., Masmiquel, L., Kumar, H., Sargin, M., Karsbøl, J. D., Jacobsen, S. H., et al. (2017). Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial. The Lancet. Diabetes & Endocrinology, 5(5), 341–354. doi:10.1016/S2213-8587(17)30092-X. Retrieved from https://pubmed.ncbi.nlm.nih.gov/28385659/ 
2. American Diabetes Association (ADA). (2021). 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2021. Diabetes Care, 44(Suppl 1), S111–S124. doi:10.2337/dc21-S009. Retrieved from https://diabetesjournals.org/care/article/44/Supplement_1/S111/31020/9-Pharmacologic-Approaches-to-Glycemic-Treatment 
3. Anderson, S. L., Beutel, T. R., & Trujillo, J. M. (2020). Oral semaglutide in type 2 diabetes. Journal of Diabetes and its Complications, 34(4), 107520. doi:10.1016/j.jdiacomp.2019.107520. Retrieved from https://pubmed.ncbi.nlm.nih.gov/31952996/ 
4. Blundell, J., Finlayson, G., Axelsen, M., Flint, A., Gibbons, C., Kvist, T., et al. (2017). Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity. Diabetes, Obesity & Metabolism, 19(9), 1242–1251. doi:10.1111/dom.12932. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5573908/ 
5. Davies, M., Pieber, T. R., Hartoft-Nielsen, M. L., Hansen, O., Jabbour, S., & Rosenstock, J. (2017). Effect of Oral Semaglutide Compared With Placebo and Subcutaneous Semaglutide on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Clinical Trial. JAMA Journal of the American Medical Association, 318(15), 1460–1470. doi:10.1001/jama.2017.14752. Retrieved from https://jamanetwork.com/journals/jama/fullarticle/2657376 
6. GoodRx-a. (2022). Rybelsus. Retrieved Feb. 10, 2022 from https://www.goodrx.com/rybelsus 
7. GoodRx-b. (2022). Ozempic. Retrieved Feb. 10, 2022 from https://www.goodrx.com/ozempic 
8. Marso, S. P., Bain, S. C., Consoli, A., Eliaschewitz, F. G., Jódar, E., Leiter, L. A., et al. (2016). Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. The New England Journal of Medicine, 375(19), 1834–1844. doi:10.1056/NEJMoa1607141. Retrieved from https://www.nejm.org/doi/10.1056/NEJMoa1607141?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200www.ncbi.nlm.nih.gov 
9. Shaefer, C. F., Jr, Kushner, P., & Aguilar, R. (2015). User’s guide to mechanism of action and clinical use of GLP-1 receptor agonists. Postgraduate Medicine, 127(8), 818–826. doi:10.1080/00325481.2015.1090295. Retrieved from https://pubmed.ncbi.nlm.nih.gov/26371721/#:~:text=The%20GLP%2D1RAs%20have%20been,consequent%20low%20risk%20for%20hypoglycemia
10. Sorli, C., Harashima, S. I., Tsoukas, G. M., Unger, J., Karsbøl, J. D., Hansen, T., et al. (2017). Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. The Lancet. Diabetes & Endocrinology, 5(4), 251–260. doi:10.1016/S2213-8587(17)30013-X. Retrieved from https://pubmed.ncbi.nlm.nih.gov/28110911/ 
11. United States Food and Drug Administration (FDA-a). (2019). Highlights of Prescribing Information: Rybelsus. Retrieved on Feb. 8, 2022 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/213051s000lbl.pdf 
12. United States Food and Drug Administration (FDA-b). (2019). Highlights of Prescribing Information: Ozempic. Retrieved on Feb. 8, 2022 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209637lbl.pdf

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