Rybelsus vs. Ozempic: 4+ differences & which to choose

Rybelsus and Ozempic are brand-name medications that contain the active ingredient semaglutide. Both are approved by the US Food and Drug Administration (FDA) to help manage type 2 diabetes. But they can also be prescribed off-label for weight loss. 

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

When it comes down to it, you might:  

• Choose Rybelsus if you prefer to take an oral pill daily. 

• Choose Ozempic if you want stronger results and you’re able to take a weekly injection.

However, everyone is different. So, there’s no one-size-fits-all answer to whether you should take Ozempic or Rybelsus. Plus, your healthcare provider is the best person to help you determine which medication makes the most sense for you. 

Still, a well-rounded understanding of Rybelsus vs. Ozempic can help you have a more informed conversation with your provider. After all, knowledge is power. 

So, let’s get started, beginning with some top-line comparisons:

• Form: Ozempic is a once-weekly injection, while Rybelsus is a once-daily oral pill.

• Active ingredient: Both contain semaglutide, a GLP-1 receptor agonist that mimics a natural hormone to help control blood sugar, slow digestion, and curb appetite.

• Effectiveness: Ozempic generally leads to greater average weight loss and blood sugar (A1C) reduction than Rybelsus.

• Dosing: Rybelsus must be taken on an empty stomach with strict timing, while Ozempic has fewer day-to-day rules.

• FDA indications: Both are approved to manage blood sugar levels in adults with type 2 diabetes, alongside lifestyle changes, and to lower cardiovascular risk in adults with type 2 diabetes. Ozempic is also approved to reduce the risk of kidney failure in adults with type 2 diabetes and chronic kidney disease. 

• Side effects: The two share similar gastrointestinal side effects (e.g. nausea, vomiting, diarrhea), which are often more pronounced during dose increases.

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Ozempic is generally more effective than Rybelsus at lowering blood sugar and reducing weight. 

The highest daily Rybelsus dose of 14 mg delivers about the same effect as a lower weekly dose of  0.5 mg of Ozempic. This means Rybelsus is roughly equal to taking one of the lower-doses of Ozempic, which is why Ozempic can lead to better blood sugar control and weight loss. 

Blood sugar control

• While it didn’t directly compare Rybelsus and Ozempic, a 2017 clinical trial found that Ozempic (1 mg weekly) lowered A1C levels by 1.9%, On the other hand, Rybelsus lowered A1C levels by 0.7%–1.9%, depending on the dose. 

• In a 2021 study, Ozempic lowered A1C by 1.6% by 30 weeks and Rybelsus by 1.4% over 26 weeks. 

Weight management

• The 2017 clinical trial found Ozempic reduced weight by about 14 pounds at 26 weeks on the 1 mg dose. Rybelsus reduced weight by about 4.5–15 pounds, depending on the dose.

• The 2021 study showed a body weight decrease of 9.9 pounds with Ozempic and 8.2 pounds with Rybelsus.

• A 2025 study of 82 people taking a 14 mg dose of Rybelsus had an average weight loss of 5.7%, or about 13 pounds, after one year. 

Cardiovascular health

• One 2025 study found Rybelsus reduced the risk of cardiovascular events by 14% in people with type 2 diabetes. But there was no improvement in kidney disease or heart failure.

• 2025 research found Ozempic reduced the risk of a major cardiovascular event (such as heart attack or stroke) by 23% in people with type 2 diabetes.

Rybelsus is taken as an oral pill once daily in the morning, at least 30 minutes before eating or drinking.  It should be swallowed whole with a small sip of water (no more than 4 ounces). 

Ozempic is given as a subcutaneous (under-the-skin) injection once weekly in the stomach, thigh, or upper arm. While you can inject Ozempic yourself, you might want to ask a friend or family member for help when using the upper arm injection site. 

Rybelsus and Ozempic are dosed differently.

The initial doses of both medications aren’t high enough to effectively control blood sugar levels. After a certain number of days, the medication dosages are increased as needed until your blood sugar is where it should be, according to your healthcare provider.

Rybelsus comes in two formulations, each with its own dosing schedule. This table shows the different doses of both Rybelsus and Ozempic.

*Some people may stay on this Rybelsus dose long-term if it works well to control blood sugar levels.

Rybelsus and Ozempic have the same list price: $997.58. They both come as brand-name medications; generic forms are not yet available. 

The costs of both Ozempic and Rybelsus can vary depending on insurance coverage, your pharmacy, and whether or not you’re eligible for savings programs. 

Insurance coverage

Insurance plans may cover Rybelsus or Ozempic as long as they’re prescribed for FDA-approved uses, such as type 2 diabetes or cardiovascular risk reduction. Contact your insurance carrier directly or refer to your plan’s drug formulary to find out if treatment is covered. 

If you’re interested in Ozempic (vs. Rybelsus), you can also use Ro’s (free!) GLP-1 Insurance Coverage Checker.  

Medicare Part D coverage

Ozempic and Rybelsus may be covered under Part D of Medicare as long as it’s been prescribed for an approved indication

How to save

You can pay as little as $25 for a one-, two-, or three-month prescription with an Ozempic savings card as long as you meet eligibility requirements. 

Rybelsus has a savings card as well, where you can pay as little as $25 for a one-, two-, or three-month prescription. You must meet eligibility requirements. 

Get Ozempic or Rybelsus at a highly reduced rate, or no cost with the Novo Nordisk’s Patient Assistance Program (PAP).

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Both Ozempic and Rybelsus can be used to help treat diabetes and diabetes-related  health conditions. 

Ozempic and Rybelsus are both FDA-approved to control blood sugar in adults with type 2 diabetes, along with diet and exercise. 

In clinical trials: 

• People with type 2 diabetes who took Rybelsus reduced their A1C significantly more than those who took a placebo. 

• 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. 

Both medications are also approved to help lower the risk of major cardiovascular events like heart attack and stroke in people with type 2 diabetes. More specifically:

• Ozempic’s cardiovascular approval includes people with type 2 diabetes and established cardiovascular disease.

• Rybelsus’ cardiovascular approval includes people who have type 2 diabetes and are at high risk for cardiovascular events.  

But if you have type 2 diabetes and chronic kidney disease (CKD), Ozempic may be a better choice than Rybelsus. 

• Ozempic is  approved to lower the risk of kidney decline, kidney failure,and death in people who are diagnosed with type 2 diabetes and CKD. 

• Rybelsus, on the other hand, doesn’t have this approval. 

Rybelsus and Ozempic can also be prescribed off-label to help treat obesity and overweight when combined with diet and exercise. Off-label means it’s for a use that isn’t explicitly FDA-approved but is an appropriate treatment in the healthcare provider's judgment. 

• In one trial, people with diabetes taking 1 mg of once-weekly semaglutide, along with diet and exercise, saw an average weight loss of 7% of their body weight over 68 weeks.

Rybelsus and Ozempic share similar side effects. 

Common digestive side effects can include: 

• Nausea

• Upset stomach

• Vomiting

• Decreased appetite

• Constipation

• Diarrhea

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

• Allergic reactions (signs like chest tightness, difficulty breathing, rashes or hives, and flushing)

• Pancreatitis (inflammation of the pancreas)

• Hypoglycemia (low blood sugar)

• Severe digestive side effects that lead to dehydration and related kidney problems

• Vision problems (e.g. blurred vision or diabetic retinopathy) 

You shouldn’t take Rybelsus or Ozempic if you have certain health conditions, such as:

• Pancreatitis

• A personal or family history of thyroid cancer, especially medullary thyroid carcinoma

• A personal or family history of multiple endocrine neoplasia syndrome type 2 (MEN-2)

• Type 1 diabetes

• Currently pregnant or breastfeeding

According to the prescribing information for both Rybelsus and Ozempic, these medications 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. 

• Some oral medications: Certain medications, including the thyroid medication levothyroxine, may require closer monitoring by your healthcare provider while taking Rybelsus or Ozempic. Also, Rybelsus may not work effectively if taken at the same time as any other oral medication — be sure to wait 30 minutes after taking it before taking other pills.

Point being: Some medications may interact with Rybelsus and Ozempic. Talk with your healthcare provider about all the other medications you take prior to starting either medication.

Rybelsus and Ozempic are both brand names of the same drug, semaglutide. They’re part of a class of medications called glucagon-like peptide 1 (GLP-1) receptor agonists.

Healthcare providers sometimes prescribe GLP-1 medications to manage type 2 diabetes, especially if other medications, like metformin, aren’t effective enough. 

GLP-1s like Rybelsus and Ozempic work to:

• Make your pancreas produce insulin to lower blood sugar

• Lower the amount of sugar that your intestines absorb

• Send signals to the brain to control appetite, causing you to eat less (which can lead to weight loss)

When choosing between Rybelsus and Ozempic, there are a few factors to consider.

Choose Rybelsus if: 

• You would rather take a daily pill over a shot.

• You don’t mind having to time the medication 30 minutes before eating or drinking every day.

• You could benefit from lowering your risk of heart attack and stroke.

Choose Ozempic if: 

• You prefer the convenience of a once-weekly shot over remembering to take a pill every morning.

• You want stronger results than you can get on Rybelsus.

• You have chronic kidney disease and want to lower your risk of kidney failure.

• You already have a cardiovascular condition like high blood pressure or heart disease and want to lower your risk of a heart attack or stroke.

Talk with your healthcare provider about your medication options. While both medications have the same active ingredient, semaglutide, there are some things you’ll have to weigh when making a decision. 

Rybelsus and Ozempic are both GLP-1 medications with the same active ingredient, semaglutide. Both are FDA-approved for blood sugar control and cardiovascular risk reduction in certain adults with type 2 diabetes. And both can be prescribed off-label for weight loss. But here are some differences to keep in mind when choosing between the two:

• Ozempic is approved to help lower the risk of worsening kidney complications in people who have both type 2 diabetes and chronic kidney disease. Rybelsus doesn’t have this approval. 

• Rybelsus is a daily pill, but it needs to be carefully timed before eating or drinking in order to get the full effects. 

• Ozempic is a weekly injection that you don’t have to take at a certain time. 

• Ozempic typically leads to stronger results for blood sugar and weight loss than Rybelsus, but both options can be effective.