Rybelsus vs. Ozempic: differences and similarities

You may have heard of Ozempic (semaglutide), a weekly injectable medication for type 2 diabetes that is often prescribed off-label for weight loss. But did you know there’s an oral version of semaglutide, too? Rybelsus and Ozempic are both brand-name type 2 diabetes medications your healthcare provider may prescribe if your current drug regimen isn’t working effectively.

Continue reading to learn more about Rybelsus vs. Ozempic, including similarities, differences, cost, side effects, and more. 

Rybelsus is an oral form of the drug, 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.

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. Usually, you take 7 mg daily for another 30 days. ​​After this, your provider will decide if this dose benefits you or if it needs to be increased to 14 mg for better blood sugar management.

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. 

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 2 mg weekly. 

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.

GLP-1 attaches to a protein called the GLP-1 receptor, which is found in your pancreas, brain, stomach, and intestines. When GLP-1 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, which leads to weight loss.

Clinical trials show that both medications are effective at treating type 2 diabetes and lowering blood sugar levels.

Novo Nordisk, the manufacturer of Rybelsus and Ozempic, says that patients treated with once-weekly Ozempic 0.5 mg subcutaneous injection can be switched over to Rybelsus 7 mg or 14 mg without any other changes to their dosing regimen. In other words: for blood sugar control, a daily dose of 7 mg or 14 mg of Rybelsus is equivalent to the 0.5 mg weekly dose of Ozempic. Ozempic may also provide additional benefits not yet proven to be associated with Rybelsus, including a lower risk of heart attack, stroke, or death due to heart problems in certain people.

Ozempic and Rybelsus are both approved by the U.S. Food and Drug Administration (FDA) to treat type 2 diabetes. They can also be prescribed off-label to help treat obesity and overweight when combined with diet and exercise. 

Rybelsus uses

Rybelsus is FDA-approved for people who have type 2 diabetes. Along with a healthy diet and exercise, it lowers blood sugar. 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. 

Ozempic uses

Ozempic is also FDA-approved for people with type 2 diabetes. Your healthcare provider may prescribe Ozempic for:

• 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. 

• 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 lower risk of cardiovascular disease than those who took a placebo. 

So far, only one brand of semaglutide, an injectable drug called Wegovy (see Important Safety Information), is FDA-approved for weight loss.

However, some healthcare providers may prescribe Ozempic off-label for weight loss, meaning for a use that isn’t explicitly FDA-approved but is an appropriate treatment in the healthcare provider's judgment. Studies have demonstrated that Ozempic may help control appetite and reduce body fat. In one trial, people with diabetes taking 1.0 mg of semaglutide (a common Ozempic dosage), along with diet and exercise, saw an average weight loss of 7% of their body weight over 68 weeks. 

Rybelsus and Ozempic are both effective to lower blood sugar. However, the medications differ in available dosage. 

Ozempic dosage

Your healthcare provider will typically prescribe 0.25 mg once weekly to start. This dose isn’t high enough to lower your blood sugar–the low dose is intended to help your body adjust to the medication and reduce the risk of side effects.

After at least one month, the dose is usually raised to 0.5 mg once weekly. Your healthcare provider may further adjust the dose if needed. The highest dose is 2 mg once weekly. Healthcare providers typically recommend this dose if you need additional blood sugar control after the 1 mg weekly injection.

Rybelsus dosage

Rybelsus is usually prescribed at a starting dose of 3 mg by mouth once daily. Like Ozempic, this dose is intended to help your body adjust to the medication and reduce the risk of side effects. After one month, the dose is typically raised to 7 mg. If this dose is not effective, your provider may raise your dose again to a maximum dose of 14 mg once daily.

Will Rybelsus be available in a higher dose?

A study of larger doses of oral semaglutide (like Rybelsus) found promising results. The trial of 10,000 participants with type 2 diabetes found the following:

• 14 mg daily reduced blood sugar by 1.5% and weight by 9.9 lbs.

• 25 mg daily reduced blood sugar by 1.9% and weight by 15.4 lbs.

• 50 mg daily reduced blood sugar by 2.2% and weight by 20.3 lbs.

And, new data released by Novo Nordisk in June 2023 found that obese or overweight people without type 2 diabetes who took 50 mg of oral semaglutide lost 15% of their body weight, on average, after 68 weeks. 

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.

Severe side effects of Rybelsus and Ozempic are rare but include:

• 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-1s. 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-1s alone, 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: 

• 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)

• Currently pregnant or breastfeeding

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: 

• 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.

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 30 7 mg Rybelsus tablets can range from $905 to $997. The list price of a 1 mg Ozempic pen is $935.7, according to Novo Nordisk. 

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.

If you have type 2 diabetes and your current treatment plan is not effectively lowering your blood pressure and helping you achieve your weight loss goals, talk to your provider about Rybelsus and Ozempic. They will help you determine which medication, if either, is right for you. For a condensed list of similarities and differences between Rybelsus vs. Ozempic, see the table below.

Key similarities and differences between Rybelsus and Ozempic include:

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Every article on Health Guide goes through rigorous fact-checking by our team of medical reviewers. Our reviewers are trained medical professionals who ensure each article contains the most up-to-date information, and that medical details have been correctly interpreted by the writer.

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Current version

June 28, 2023

Written by

Gina Allegretti, MD

Fact checked by

Felix Gussone, MD

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About the medical reviewer

Felix Gussone, MD, Ro

Felix Gussone is a physician, health journalist and a Manager, Medical Content & Education at Ro.