Healthcare provider discussing Rybelsus® vs. Ozempic® with a patient in office

Rybelsus® vs. Ozempic®: What's the Difference?

Written on June 25, 2023 by Amy Harris, MS, RN, CNM. To give you technically accurate, evidence-based information, content published on the Everlywell blog is reviewed by credentialed professionals with expertise in medical and bioscience fields.

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If you live in a larger-sized body, have type 2 diabetes, or are worried about your risk for chronic conditions such as heart or kidney disease, you may wonder whether some of the newer weight loss drugs could work for you. With so many on the market, knowing which is right for you can take a lot of work. With hefty price tags and possible side effects, it can feel like a high-stakes decision. Here, we break down the difference between two commonly-prescribed medications used to treat type 2 diabetes and obesity — Rybelsus® and Ozempic®.

What is Rybelsus®?

Rybelsus® is the medicine semaglutide in a pill form. Rybelsus® is prescribed to control blood glucose (sugar) levels in adults with type 2 diabetes. It can be used on its own when metformin (another diabetes medicine) cannot be used or in combination with other diabetes medicines.[1] It is taken once a day in tablets containing either 3, 7, or 14 milligrams of semaglutide.[2]

The U.S. Food and Drug Administration (FDA) has not yet approved Rybelsus® for treating obesity. Nevertheless, many health providers prescribe Rybelsus® “off-label” to people living with obesity. Off-label means that your provider is prescribing a medication for a use (weight loss and obesity treatment) other than its stated purpose (treatment of type 2 diabetes).[3]

What is Ozempic®?

Ozempic® is an injectable form of the same medicine (semaglutide). It is also FDA-approved to treat type 2 diabetes. It is used with diet and exercise to help control your blood sugar.[4] This medicine may also lower the risk of heart attack, stroke, or death in people with type 2 diabetes and heart or blood vessel disease.[5]

The FDA approved Ozempic® on June 4, 2021, for the treatment of “chronic weight management in adults with obesity or overweight with at least one weight-related condition (such as high blood pressure, type 2 diabetes, or high cholesterol), for use in addition to a reduced calorie diet and increased physical activity."[6]

Do Rybelsus® and Ozempic® Both Work the Same Way?

Yes. They are both GLP-1 agonists. These medications lower blood sugar levels by mimicking a hormone called glucagon-like peptide 1, which helps the pancreas produce insulin.[7] These two medications cause your pancreas to produce more insulin after meals. GLP-1 agonists also make it harder for your liver to make glucose, keeping post-meal spikes in blood sugar low and lowering hemoglobin A1C.

But how do the GLP-1 agonists work for weight loss? Both medications also keep food in the stomach longer so that you feel full sooner and eat less.[8] Semaglutide has also been shown to decrease your appetite.[9]

In these ways, Rybelsus® and Ozempic® help keep your blood sugar levels healthy and can lead to weight loss.[2,4-5]

What are the Biggest Differences Between Rybelsus® and Ozempic®?

Because they are just different dosage forms of the same medication, Rybelsus® and Ozempic® really aren’t that different. The major differences are:

  • Rybelsus® is taken in pill form once a day.
  • Rybelsus® must be taken in the morning at least 30 minutes before you eat, drink, or take other medications.[2]
  • Ozempic® comes in a once-weekly, self-injectable, pre-filled syringe.
  • Ozempic® can be prescribed for weight loss and risk reduction for cardiovascular disease, whereas Rybelsus can only treat obesity off-label.[5]

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How are Rybelsus® and Ozempic® Similar?

Rybelsus® and Ozempic® are made from the same medication, just in different forms. Therefore, their side effects, the way they work, and treatment effects are very similar. Both medications[2,4,7,8,10]:

  • Are used to treat type 2 diabetes
  • Cause weight loss as a side effect
  • Do not yet have generic versions
  • Are made from semaglutide and are GLP-1 agonists
  • Can result in improvement in blood pressure and cholesterol levels to healthier levels
  • Can cause similar side effects: nausea, diarrhea, and abdominal cramps
  • Are not approved for use in pregnant people, people planning a pregnancy in the next two months, breastfeeding people, or people planning to breastfeed
  • Can cause problems for people with pancreatitis, kidney disease, gallbladder disease, diabetic retinopathy, or depression
  • Do increase your chances of thyroid cancer

Which Medication Works Better for Weight Loss — Rybelsus® or Ozempic®?

How much weight you lose while taking semaglutide can depend on which GLP-1 drug you use and your dose.[8] Studies have found that all GLP-1 medicines can lead to a weight loss of about 10 to 15 pounds.[11] Studies found people using semaglutide and making lifestyle changes lost about 34 pounds versus 6 pounds in those who didn’t use the drug.[11] It is important to note that the duration of this study was one year — researchers are still studying how effective both of these medicines are for long-term weight maintenance.

Ultimately, the medication that will work best for weight loss is the one that you can access and afford, causes the fewest side effects, and is easiest for you to take. Insurance coverage for weight loss medications can vary depending on your particular plan, other pre-existing conditions you might have, and what other treatments you might have already tried.

Clinically significant, successful, and sustainable weight loss takes time and effort. Neither Rybelsus® nor Ozempic® is meant to be taken for a few months to drop some pounds quickly. Instead, think of them as more like a medicine taken for a chronic condition, such as high blood pressure, for the rest of your life. Finding your healthiest, most sustainable weight may take a combination of diet and activity changes, medications, and other healthy habits you adopts as your permanent healthy lifestyle.

Help with Weight Management via Everlywell

Now that you know more about the differences between Rybelsus® and Ozempic®, you may want to learn how to get a prescription. Or you may have questions about side effects. Ozempic® and Rybelsus® may not be safe for you to take, depending on your medical history (if you have a history of pancreatitis, for example) or other medical conditions (like diabetic retinopathy or planning a pregnancy in the next two months). That is why it is best to discuss whether or not a prescription for Rybelsus® or Ozempic® is suitable for you with a healthcare provider experienced in the treatment of obesity.[9]

It can sometimes be difficult to find the right healthcare provider who understands you and your weight management journey. That is why Everlywell offers convenient, affordable, expert telehealth care from the privacy and comfort of your home. The licensed healthcare providers (nurse practitioners) via Everlywell's comprehensive Weight Care+ Program can offer GLP-1 agonist prescriptions, regular telehealth visits, and support for related conditions to those 18 years and older who meet safety guidelines. All prescriptions are subject to the clinician’s judgment.

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  1. Rybelsus (Semaglutide). European Medicine Agency. Published May 27, 2020. Accessed June 7, 2023.
  2. Rybelsus® Prescribing Information. Accessed June 2023.
  3. Understanding unapproved use of approved drugs off-label. FDA. Published February 5, 2018. Accessed June 7, 2023.
  4. Ozempic® Prescribing Information. Accessed June 2023.
  5. Sally Hughes, Joshua J. Neumiller; Oral Semaglutide. Clin Diabetes 1 January 2020; 38 (1): 109–111.
  6. FDA approves new drug treatment for chronic weight management, first since 2014. FDA. Published June 4, 2021. Accessed June 7, 2023.
  7. GLP-1 agonists. Johns Hopkins Patient Guide to Diabetes. Johns Hopkins. Accessed June 2023.
  8. Semaglutide (subcutaneous route). Drugs and supplements. Mayo Clinic. Published March 1, 2023. Accessed June 2023.
  9. Should you take Ozempic for weight loss? Cleveland Clinic. Published March 30, 2023. Accessed June 2023.
  10. Semaglutide Injection. MedlinePlus. NIH. Published February 15, 2023. Accessed June 7, 2023.
  11. O’Neil PM, Birkenfeld AL, McGowan B, et al. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet. 2018;392(10148):637-649.
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