Rybelsus vs. Ozempic: 4 Differences Between Oral and Injectable Semaglutide for Diabetes

Glucagon-like peptide-1 (GLP-1) receptor agonists are a large and growing class of medications. Of these, Ozempic (semaglutide) is a popular injectable option for Type 2 diabetes. But did you know that Ozempic’s active ingredient is also available as an oral pill?

Rybelsus is an oral version of semaglutide for Type 2 diabetes. It works the same way in the body as Ozempic to manage blood glucose (sugar) levels. So why give yourself an injection when you can just swallow a tablet?

Key differences between Rybelsus and Ozempic

While Rybelsus and Ozempic have several similarities, there are a few key differences to consider. Here’s a quick summary of the differences between these medications.

Below, we take a closer look at four key differences between Rybelsus and Ozempic.

1. Rybelsus and Ozempic come in different dosage forms

Even though Rybelsus and Ozempic contain the same active ingredient, they come in different dosage forms. Rybelsus is the oral form of semaglutide, while Ozempic is the injectable form.

Rybelsus comes as an oral tablet that’s available in two different formulations. The first (R1) comes in 3 mg, 7 mg, and 14 mg doses. The second (R2) formulation has improved absorption, allowing for lower semaglutide doses. It comes in 1.5 mg, 4 mg, and 9 mg doses. Rybelsus tablets are sensitive to moisture, heat, and light, so they should be stored in their original container.

Ozempic comes in a prefilled, multi-dose injection pen. It’s available in four doses: 0.25 mg and 0.5 mg (red pen), 1 mg (blue pen), and 2 mg (yellow pen). Unused Ozempic pens last longest in the refrigerator. After first use, an Ozempic pen can be stored in the refrigerator or at room temperature for up to 56 days.

2. Rybelsus is taken daily, while Ozempic is injected weekly

Another difference between Rybelsus and Ozempic is dose frequency. To achieve a consistent amount of medication in the body, Rybelsus needs to be taken daily. Ozempic, on the other hand, is injected once weekly.

Semaglutide lasts a long time in the body — whether you take it by mouth or inject it. But the amount you absorb with each route is different. When you take it orally, you only absorb a small amount of semaglutide (less than 1%). Taking Rybelsus daily allows these small amounts to build up in your body. A larger amount of semaglutide is absorbed with the injection (over 80%), which is why Ozempic is injected once a week.

To get the most from Rybelsus, take it first thing in the morning, on an empty stomach with up to 4 oz (120 mL) of water. Wait at least 30 minutes before eating or drinking, or taking other medications.

3. Both Ozempic and Rybelsus have proven cardiovascular benefits

Rybelsus and Ozempic are approved to treat Type 2 diabetes in adults. But they also provide cardiovascular benefits for this population.

Both medications are approved to lower the risk of major adverse cardiovascular events (MACE) — heart attack, stroke, or cardiovascular death — in certain people with Type 2 diabetes. Ozempic is approved to lower the risk of MACE in adults with established heart disease, while Rybelsus is approved for those at high risk for these events.

Depending on your medical history and risk factors, your healthcare team may recommend Rybelsus or Ozempic to manage your cardiovascular risk.

4. Ozempic may be a good option if you also have chronic kidney disease

In addition to its cardiovascular benefits, Ozempic is also approved for kidney protection in people with both Type 2 diabetes and CKD. If you have both health conditions, Ozempic may be a better fit.

During clinical trials, Ozempic was shown to lower the risk of major kidney disease-related events by 24% in this group. This type of clinical trial hasn’t been done with Rybelsus. But it’s possible that some people taking it may see kidney-related benefits while taking it.

How much weight can you lose with Rybelsus or Ozempic?

Neither Rybelsus nor Ozempic are approved for weight loss. But people taking them often report losing weight.

One real-world study looked at Rybelsus (7 mg or 14 mg) and Ozempic (0.5 mg or 1 mg) and found similar weight loss between the medications — about 13 lbs to 14 lbs at 6 months. Ozempic is also available in a 2 mg dose. But compared to the 1 mg Ozempic dose, the difference in weight loss may not be significant.

Good to know: Semaglutide is also available in a higher-dose injection and an oral pill for weight loss called Wegovy. The pill contains 25 mg of oral semaglutide, which has shown weight loss comparable to the highest Wegovy dose (2.4 mg).

Does Rybelsus have fewer side effects than Ozempic?

Not really. Rybelsus and Ozempic can cause similar side effects, which are mostly gastrointestinal. But Ozempic can also cause injection site reactions, such as redness and swelling where you inject your dose.

Other common Rybelsus and Ozempic side effects include:

• Nausea

• Vomiting

• Stomach pain

• Diarrhea

• Constipation

• Decreased appetite

Less common, but potentially serious side effects and risks include:

• Severe allergic reactions, including anaphylaxis

• Pancreatitis (inflammation of the pancreas)

• Gallbladder problems, including gallstones

• Acute kidney damage

Both Rybelsus and Ozempic have a boxed warning (the FDA’s strongest medication warning) about an increased risk of thyroid C-cell tumors. For this reason, you shouldn't use either medication if you have a personal or family history of medullary thyroid cancer, or if you have multiple endocrine neoplasia type 2.

Can you switch from Ozempic to Rybelsus?

Yes, it’s possible to switch from Ozempic to Rybelsus. But this can depend on your treatment goals, health history, and dose.

According to the manufacturer, people using the 0.5 mg Ozempic dose can switch to the 7 mg or 14 mg (or 4 mg or 9 mg) Rybelsus dose. After your last Ozempic dose, you’ll wait 7 days before starting Rybelsus.

The manufacturer doesn’t have specific instructions for switching from the 0.25 mg, 1 mg, or 2 mg Ozempic doses to Rybelsus.

How can you decide if Rybelsus or Ozempic will be right for you?

Choosing between Rybelsus and Ozempic can depend on factors such as your treatment goals and preferences:

• Formulation: Rybelsus is a daily pill, while Ozempic is a weekly injection. If you want a needle-free option, Rybelsus can be a good choice. But it also has specific instructions to follow when taking it to ensure you absorb your dose.

• Additional benefits: Both medications offer cardiovascular benefits for certain people. But Ozempic is also approved for its kidney benefits. If you have Type 2 diabetes and CKD, Ozempic may be a better choice.

• Treatment goals: Ozempic offers higher doses (up to 2 mg weekly), which may be more effective than the maximum Rybelsus dose (14 mg or 9 mg).

Your healthcare team can work with you to determine which medication fits your treatment plan, lifestyle, and preferences.

How to save on Ozempic and Rybelsus

Ozempic and Rybelsus are only available as brand-name medications. But GoodRx can help you navigate ways to save on your prescription.

• GoodRx coupon: If you’re new to using GoodRx for Ozempic savings, pay an introductory price of $199 per month for the first two fills (only available for certain doses). After that, most ongoing fills are priced at $349 per month, depending on the dose. You can also save 14% off the average retail price of Rybelsus.

• Manufacturer copay card: If you’re eligible, you could pay as little as $25 per month for Ozempic or $25 per prescription for Rybelsus with a copay savings card.

• Patient assistance program: If you’re uninsured or underinsured, you may be eligible for Ozempic or Rybelsus patient assistance programs, which offer the medication at no charge.

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Written by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

Reviewed by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

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