Rybelsus vs. Ozempic: What’s the Difference Between Oral and Injectable Semaglutide?

Key takeaways:

Rybelsus and Ozempic are two medications used to treat Type 2 diabetes in adults. They both contain semaglutide, but Rybelsus is a pill and Ozempic is an injection.
Rybelsus needs to be taken every day to achieve consistent levels in the body. Ozempic only needs to be injected once a week. This is due to absorption differences between oral and injectable semaglutide.
Ozempic is also approved to lower the risk of serious cardiovascular and kidney disease-related problems in certain people. Rybelsus isn’t approved for these uses yet.
Rybelsus and Ozempic aren’t approved for weight loss. But some people lose weight while taking them. Real-world studies have found comparable weight loss between the two medications.

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.

	Rybelsus	Ozempic
Approved uses	Type 2 diabetes in adults	Type 2 diabetes in adults Lower the risk of major adverse cardiovascular events for people with heart disease and Type 2 diabetes Lower the risk of major kidney disease-related events in people with Type 2 diabetes and chronic kidney disease (CKD)
Form	Oral tablet	Injection
Frequency	Daily: In the morning, at least 30 minutes before food, drink, and other medications	Weekly, at any time of day
Typical dosage	Starting dosage: 3 mg daily (1.5 mg daily for R2 formulation) Maximum dosage: 14 mg daily (9 mg daily for R2 formulation)	Starting dosage: 0.25 mg weekly Maximum dosage: 2 mg weekly
Storage	Must be stored in original container at room temperature	Unused: Store in the refrigerator After first use: Store in refrigerator or at room temperature for up to 56 days

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.

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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. Ozempic may be a good option if you also have heart disease

Rybelsus and Ozempic are both approved to treat Type 2 diabetes in adults. But Ozempic is also approved for heart-related benefits for people with both Type 2 diabetes and heart disease.

EXPERT PICKS: WHAT TO READ NEXT

How to save: Glucagon-like peptide-1 (GLP-1) medications like Ozempic don’t need to break the bank. Explore ways to save on your prescription with this GLP-1 savings guide.
Rybelsus for weight loss: Learn more about Rybelsus for weight loss, from potential benefits to when it might be available.
Knowing the risks: Compounded products can offer options when medications are in shortage or there’s a specific medical need. But before giving compounded semaglutide a try, it’s a good idea to understand the potential risks.

Ozempic is approved to lower the risk of major cardiovascular events (heart attack, stroke, or cardiovascular death), or MACE, in this group. During clinical trials, it lowered the risk of MACE by 26%. Rybelsus has been shown to lower the risk of MACE by 14%. It’s not currently approved for this use, but that could change in 2025.

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 for weight loss called Wegovy. Wegovy is approved for certain adults and adolescents ages 12 and older. The FDA is also reviewing a pill version of Wegovy that could be approved by the end of 2025. The pill contains 25 mg of oral semaglutide, which has shown weight loss comparable to the highest Wegovy dose (2.4 mg).

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: Ozempic is approved for uses beyond diabetes alone. If you have Type 2 diabetes and heart disease or 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.

Manufacturer copay card: If you’re eligible, you could pay as little as $25 for Ozempic or $10 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.
GoodRx coupon: With a free GoodRx discount, you could pay as little as $499 per month for Ozempic. You can also save 14% off the average retail price of Rybelsus.

Frequently asked questions

Not directly. Some people taking medications like Rybelsus have reported worsening kidney function. But this is typically linked to dehydration from severe side effects, such as vomiting or diarrhea. If you’re taking Rybelsus, be sure to drink enough fluids to avoid dehydration. Report any severe or persistent side effects to your healthcare team.

Hair loss isn’t listed as a common side effect of Rybelsus or Ozempic. But both medications can cause weight loss, which can result in hair thinning or loss in some people. The good news is that this type of hair loss usually isn’t permanent. And it’ll stop on its own after your hair follicles go back to their normal growth cycles.

Even so, it’s best to talk to your prescriber if you notice any unusual hair thinning so they can identify the cause.

The bottom line

Semaglutide is available as a weekly injection (Ozempic) and a daily tablet (Rybelsus) for Type 2 diabetes. Ozempic is also FDA approved to lower the risk of major cardiovascular and kidney disease-related events in certain people.

If you don’t want to give yourself a weekly injection, Rybelsus offers an oral alternative. But it may not be an option if you’re using higher Ozempic doses (1 mg, 2 mg). You’ll also need to follow specific instructions when taking it to help you absorb as much of your dose as possible.

Talk to your healthcare team if you have questions about which option is best for you.

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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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