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Drug vs. Drug

Rybelsus vs. Ozempic: Differences, similarities & side effects

Both Rybelsus and Ozempic are FDA approved for managing blood sugar, but they’re sometimes prescribed off-label for weight loss
Gerardo Sison medical writer headshot
By | Feb. 19, 2024
An injectioon vs a pill: Rybelsus vs. Ozempic
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When it comes to treatments for managing blood sugar levels, there are now more options than ever. Rybelsus and Ozempic are brand-name medications used to improve blood sugar in people with Type 2 diabetes. Although they’re not approved by the U.S. Food & Drug Administration (FDA) for weight management, many people find they lose weight with these medications, especially with lifestyle changes like a healthy diet and regular exercise. 

Both Rybelsus and Ozempic contain the active ingredient semaglutide and work by mimicking a hormone called GLP-1, which increases insulin production and reduces appetite. Despite their similarities, Rybelsus and Ozempic differ in how they’re administered and dosed. Insurance and Medicare coverage of these medications can also vary. 

Read on to learn more about the similarities and differences between Rybelsus and Ozempic. 

Rybelsus vs. Ozempic: Key differences

Although Rybelsus and Ozempic contain semaglutide and help lower blood sugar levels, they come in different dosage forms. Rybelsus is an oral tablet, while Ozempic is a subcutaneous injection (under the skin). Rybelsus is the first oral form of semaglutide, approved in 2017. 

Some patients may prefer a tablet over an injection for comfort or other reasons. However, Rybelsus contains a higher dose of semaglutide than Ozempic. Oral drugs need a higher dose than injected ones because they’re partly broken down in the liver before reaching the bloodstream. Injections deliver the drug directly into the blood, so less is needed for the same effect.

The standard dosage of Rybelsus is 7 milligrams (mg) once daily, taken at least 30 minutes before the first meal, drink, or other medications. Ozempic, on the other hand, is administered as a once-weekly injectable medication. The standard dosage of Ozempic is 0.5 mg once weekly at any time of the day, with or without food.

Rybelsus vs. Ozempic comparison chart
Rybelsus Ozempic
Drug class GLP-1 receptor agonist GLP-1 receptor agonist
Generic name Semaglutide Semaglutide
Forms available Oral tablet Subcutaneous injection
Standard dosage 3 mg once daily for 30 days, followed by an increase to 7 mg once daily. If additional glycemic control is needed after taking 7 mg once daily for 30 days, the dosage may be increased to 14 mg once daily.  0.25 mg injected under the skin once weekly for 4 weeks. Then, the dosage is increased to 0.5 mg once weekly. 

The dosage may be increased to 1 mg once weekly after 4 weeks on the 0.5 mg dosage and then increased again to 2 mg once daily after 4 weeks on the 1 mg dosage, depending on the treatment response.
Typical treatment length Long-term Long-term
Typical users  Adults 18 years and older Adults 18 years and older

Conditions Rybelsus and Ozempic treat

Rybelsus and Ozempic are both FDA-approved to manage blood sugar levels in adults with Type 2 diabetes alongside an appropriate diet and exercise plan. These medications are not a cure for diabetes mellitus, but they may help manage the condition and reduce the risk of complications, such as heart disease, high blood pressure, and heart attacks. 

The drug label for Ozempic specifically states it can be used to help reduce the risk of cardiovascular events like heart attacks and stroke in people with Type 2 diabetes and heart disease. This indication is not found on the label for Rybelsus. 

Rybelsus and Ozempic may help promote weight loss as a secondary benefit. Although they’re not FDA-approved for weight management, healthcare providers may prescribe them off-label. In addition, Rybelsus and Ozempic are not approved to treat Type 1 diabetes. 

Rybelsus vs. Ozempic: Conditions treated
Condition Rybelsus Ozempic
Type 2 diabetes Yes Yes
Lower the risk of major cardiovascular events, such as heart attack, stroke, and death Off-label Yes
Weight loss Off-label Off-label

Is Ozempic better than Rybelsus?

Some studies suggest Ozempic tends to reduce blood sugar more than Rybelsus. Based on clinical trials, Ozempic can lower blood sugar levels by about 1.5% to 1.8%, while Rybelsus reduces them by roughly 1.0% to 1.4%. In addition, Ozempic may be more effective than Rybelsus in promoting weight loss. However, the dosage can also make a difference, as a 14 mg dose of Rybelsus is equivalent to a 0.5 mg weekly dose of Ozempic. 

Still, Rybelsus and Ozempic have both been shown to be effective for managing Type 2 diabetes. After all, they are different forms of the same diabetes medication. The best choice will depend on the patient’s lifestyle and preferences. For example, some patients may prefer taking a daily pill over an injectable medication. 

Consult a healthcare provider to determine the best treatment option. They can recommend the best choice based on your medical history and other medications you take. 

Rybelsus vs. Ozempic: Insurance coverage and cost comparison

Rybelsus and Ozempic are brand-name prescription medications manufactured by Novo Nordisk. They’re not currently available in lower-cost generic forms. In most cases, Rybelsus and Ozempic are covered by Medicare and private insurance plans when prescribed for Type 2 diabetes. They’re generally not covered for off-label purposes like weight management. 

The extent of insurance coverage for these medications can vary. Even with coverage, you may be responsible for out-of-pocket costs, such as copays or coinsurance. For those without insurance or adequate coverage, a SingleCare prescription discount card may help reduce the retail costs of the medications. 

Rybelsus vs. Ozempic cost and coverage chart
Rybelsus Ozempic
Typically covered by insurance? Yes Yes
Typically covered by Medicare Part D? Yes Yes
Quantity 30, 7 mg tablets 1 prefilled injection pen
Typical Medicare copay Varies Varies
SingleCare cost $810 $800

Rybelsus vs. Ozempic side effects

Rybelsus and Ozempic can cause similar side effects, though not everyone will experience them. Among the common side effects these drugs share are gastrointestinal ones, such as nausea, vomiting, constipation, diarrhea, and stomach or abdominal pain. These side effects are usually mild and go away over time as the body adjusts to the medication. In rare cases, people taking Ozempic may also experience swelling, redness, or itching around the area of injection. 

Although they share similar side effects, the severity and frequency of these side effects can vary. In some cases, these medications may cause serious side effects, such as inflammation of the pancreas (pancreatitis), vision problems linked to diabetes (diabetic retinopathy), low blood sugar (hypoglycemia), and acute kidney injury. 

Rybelsus vs. Ozempic side effects comparison
Rybelsus Ozempic
Side Effect Applicable? Frequency Applicable? Frequency
Nausea Yes 11% Yes 16%
Vomiting Yes 6% Yes 5%
Diarrhea Yes 10% Yes 9%
Constipation Yes 6% Yes 5%
Decreased appetite Yes 6% Yes N/A
Stomach pain Yes 10% Yes 7%
Injection site reactions No – Yes 0.2%

Frequency is not based on data from a head-to-head trial. This may not be a complete list of adverse effects that can occur. Please refer to your healthcare provider to learn more.

Source: DailyMed (Rybelsus), DailyMed (Ozempic)

Drugs that may interact with Rybelsus and Ozempic

Rybelsus and Ozempic can interact with similar medications. Some common drug interactions with Rybelsus and Ozempic include those with insulin and that increase the secretion of insulin, such as sulfonylureas and glinides. Taking Rybelsus or Ozempic with these medications may increase the risk of hypoglycemia.

Rybelsus and Ozempic can also slow the emptying of the stomach, which can affect the absorption of oral medications. As a result, Rybelsus and Ozempic may prolong the length of time it takes for other medications to work, potentially reducing their effectiveness.

Tell your healthcare provider about any medications you take, including prescription drugs, over-the-counter medicines, and herbal supplements, before starting Rybelsus or Ozempic. 

Rybelsus and Ozempic drug interactions
Drug Drug class Rybelsus Ozempic
NovoLog (insulin aspart)

Humalog (insulin lispro)

Lantus (insulin glargine)

 Insulin  Yes Yes
Glucotrol (glipizide)

Amaryl (glimepiride)

 Sulfonylureas Yes Yes
Januvia (sitagliptin)

Tradjenta (linagliptin)

Onglyza (saxagliptin)

 DPP-4 inhibitors Yes Yes
Prandin (repaglinide)

Starlix (nateglinide)

 Glinides Yes Yes

Consult a healthcare professional for other possible drug interactions.

Rybelsus and Ozempic drug warnings

Both Rybelsus and Ozempic carry a boxed warning due to an increased risk of thyroid C-cell tumors. These medications should be avoided in people with a personal or family history of medullary thyroid carcinoma (MTC) or those who have an endocrine system condition called multiple endocrine neoplasia syndrome type 2.

The use of Rybelsus or Ozempic may carry a risk of pancreatitis, diabetic retinopathy, and hypoglycemia. In some cases, dosages may need to be adjusted or treatments discontinued if serious problems arise. 

Another potentially serious side effect is acute kidney injury. The risk of kidney problems may be higher in people who are dehydrated or those taking other medications that affect kidney function.

Seek immediate medical attention if signs or symptoms of a serious allergic reaction develop, such as hives, itching, swelling of the face or throat, or trouble breathing. 

Rybelsus and Ozempic may cause harm to an unborn baby. Therefore, they should not be used during pregnancy. It’s unknown whether Rybelsus or Ozempic can cause harm to a breastfeeding child. The label for Rybelsus recommends avoiding it while breastfeeding, while the label for Ozempic recommends consulting a healthcare provider first. 

Frequently asked questions about Rybelsus vs. Ozempic

Which is better, Rybelsus or Ozempic?

The best medication depends on personal preferences and overall medical history. People who prefer an oral medication over an injectable one may prefer Rybelsus, while those who prefer less frequent dosing might prefer Ozempic. Rybelsus and Ozempic contain the active ingredient semaglutide and are approved for adults with Type 2 diabetes. 

Why is Rybelsus so hard to get?

The availability of Rybelsus may be limited due to high demand. Ozempic has gained widespread recognition after becoming viral on social media, with many people wanting to use the medication off-label for weight loss. As an oral version of Ozempic, Rybelsus may be in higher demand for those looking for a non-injection option for managing blood sugar levels.

RELATED: Rybelsus vs. Wegovy

Is Rybelsus more expensive than Ozempic?

Rybelsus and Ozempic cost around the same price. However, the actual costs can vary based on insurance coverage, dosage, and the pharmacy. Generally, injectable medications like Ozempic may be more expensive than oral medications, but this isn’t always the case. Consult the insurance provider or pharmacy to determine the potential cost of Rybelsus or Ozempic. 

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