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

Glucagon-like peptide-1 (GLP-1) 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?

While Rybelsus and Ozempic have several similarities, there are a few key differences to consider. We cover four of these differences below.

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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 three doses: 3 mg, 7 mg, and 14 mg. The tablet is sensitive to moisture, heat, and light, so it should be stored in its 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 it’s taken 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.

EXPERT PICKS: WHAT TO READ NEXT

• Ozempic alternatives: Due to its popularity, semaglutide injections (Ozempic, Wegovy) are currently in shortage. If you can’t fill your prescription, here is a list of potential Ozempic alternatives your prescriber may consider.

• 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 help people access certain medications that are in shortage. But before giving compounded semaglutide a try, it’s a good idea to understand the potential risks.

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

Rybelsus and Ozempic are both approved for Type 2 diabetes in adults. But Ozempic has additional proven benefits for people with both Type 2 diabetes and heart disease.

Ozempic is approved to lower the risk of major cardiovascular events (heart attack, stroke, or cardiovascular death) in this group. Rybelsus is currently being studied in a longer-term trial to confirm its potential cardiovascular benefits. But until this information is available, your prescriber may determine that Ozempic is a better fit if you also have heart disease.

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

A recent study has also shown that Ozempic lowers the risk of major kidney disease-related events in people with chronic kidney disease (CKD) and Type 2 diabetes. This type of study hasn’t been done with Rybelsus. But it’s possible that some people taking it may see kidney-related benefits while taking it.

Ozempic isn’t currently approved for CKD in people with Type 2 diabetes. But the FDA could approve it for this use sometime in January 2025.

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. And higher Rybelsus doses (25 mg and 50 mg) for diabetes and weight loss may be available in the near future. The 50 mg Rybelsus dose has shown weight loss that’s comparable to Wegovy.

Can you switch from Rybelsus to Ozempic (and vice versa)?

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

According to the manufacturer, people taking the highest Rybelsus dose (14 mg) can switch to the 0.5 mg Ozempic dose. After your last Rybelsus dose, you can start Ozempic the next day. And if you’re using the 0.5 mg Ozempic dose, you can switch to the 7 mg or 14 mg Rybelsus dose. After your last Ozempic dose, you’ll wait at least 7 days before starting Rybelsus.

The manufacturer doesn’t have specific instructions for switching from Rybelsus 7 mg to Ozempic. Your prescriber can determine which Ozempic dose may be right for you.

But if you’re using the 1 mg or 2 mg Ozempic doses, you can’t switch to Rybelsus. This is because there isn’t a comparable dose. And your prescriber may have you stick with Ozempic if you also have heart disease or CKD.

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.

If you’re eligible, you could pay as little as $25 for Ozempic or $10 for Rybelsus with a copay savings card. And 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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