Rybelsus vs Ozempic: GLP-1 pill or injection -- which is best?

Rybelsus® and Ozempic® are brand-name diabetes medications with the same active ingredient—semaglutide. They’re also manufactured by the same company—Novo Nordisk. Both meds are intended to treat type 2 diabetes but are used off-label for weight loss for those with obesity. 

From the outside, both medications seem similar, so what’s the big difference between the them? A few things differentiate these medications, and we’re here to cover them all.

Here’s what we know about Rybelsus vs Ozempic. Let’s get started.

What is Ozempic?

Ozempic (semaglutide) is a once-weekly injectable medication the U.S. Food and Drug Administration (FDA) approved in 2017 to treat type 2 diabetes in adults. Ozempic is part of the drug class called glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and it works three different ways in your body. 

First, it mimics the naturally occurring GLP-1 incretin hormone in your body to communicate with your pancreas about how much insulin to produce, effectively helping to lower blood sugar levels. 

Second, Ozempic helps to control how much sugar your liver makes and releases. And finally, it delays gastric emptying (slows digestion), helping satiety and your feeling of fullness. All of these important steps help support weight loss as well. 

What is Rybelsus?

Unlike the injectable Ozempic, one of the main differences is that Rybelsus is a once-daily oral tablet version of semaglutide. It was FDA-approved two years after Ozempic in 2019 for the treatment of type 2 diabetes, and works in almost the same way. 

It’s also a GLP-1 receptor agonist and controls the sugar your liver produces, slows stomach emptying, and lowers blood glucose levels.

What are the dosages for Rybelsus vs Ozempic?

When comparing Rybelsus vs Ozempic, you'll may be curious how their dosages differ. Here's what you can expect.

Rybelsus dosages

Rybelsus is initially prescribed in a 3-mg dose. You’ll stay on that dose for 30 days while your body adjusts to the new med. Typically, your health care provider will then up your dose of Rybelsus to 7 mg for at least 30 days. Then, if you need additional glycemic control, your health care provider will increase to yourdose to 14 mg and maintain it at that level. 

You must take Rybelsus on an empty stomach first thing in the morning then wait at least 30 minutes before eating or drinking anything. And you can take Rybelsus with only four ounces of water. If you eat or drink before the 30-minute mark, you could cause the med to not be as effective in your body.

Ozempic doseages

Ozempic (semaglutide) is typically given in once-weekly injectable doses of 0.25 mg, 0.5 mg, 1 mg, or 2 mg. The starting dose is 0.25 mg weekly for the first four weeks, which helps your body get used to the medicine. At week five,  if you tolerate the medication well, your health care provider will increase the dose to 0.5 mg once weekly. Then your health care provider may increase your weekly dosage to 1 mg once weekly as long if everything goes smoothly. If you need additional blood-sugar control, your health care provider may increase the weekly dosage to 2 mg, the maximum dose of Ozempic.

Unlike Rybelsus, you can inject Ozempic on the same day during the week, once a week, at any time. So, if you choose to do it Sunday at 9:00 a.m., continue that Sunday routine each week while taking Ozempic. You can also take Ozempic with or without food.

It’s important to keep in mind and follow all recommended prescribing guidelines your doctor gives you when taking either Rybelsus or Ozempic. This ensures the drug will work properly.

Rybelsus vs Ozempic: side effects

Because Rybelsus and Ozempic are both semaglutide, the side effects—both common and rare but serious— are very similar. Here’s the breakdown of the side effects for Rybelsus vs Ozempic:

Rybelsus

Common side effects of Rybelsus:

• nausea

• diarrhea

• vomiting

• constipation

• decreased appetite

• stomach (abdominal) pain

If any of these side effects become worse or unbearable, contact your health care professional as soon as possible.

Although extremely rare, we want to make you aware of more serious side effects you could potentially have while taking Rybelsus. Here are other possible side effects.

• ​​inflammation of your pancreas (pancreatitis)

• changes in vision

• low blood sugar (hypoglycemia) 

• kidney problems (kidney failure)

• serious allergic reactions

• gallbladder problems

• possible thyroid tumors, including thyroid cancer

Ozempic

The most commonly reported side effects while taking Ozempic for weight loss are gastrointestinal issues, such as nausea, vomiting, diarrhea, constipation, and abdominal pain. 

Serious side effects:

• possible thyroid tumors, including thyroid cancer

• low blood sugar

• gallbladder problems

• inflammation of your pancreas (pancreatitis)

• kidney problems (kidney failure)

• changes in vision

• serious allergic reactions

As an important note, you shouldn’t take Ozempic or Rybelsus if you’re pregnant or planning on becoming pregnant in the next two months or if you’re currently breastfeeding. 

Both Rybelsus and Ozempic come with the warning that if you or you have a family history of medullary thyroid carcinoma (MTC) or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), you shouldn’t take either medication.

Is Rybelsus or Ozempic better for weight loss?

Most studies point toward Rybelsus being just as effective as Ozempic. Still, there are some variables involved that need to be examined before coming to that conclusion.

In a systematic review and meta-analysis of multiple studies  published in 2021 in Diabetes Therapy, they found that those given the 14 mg dose of oral semaglutide reported a body weight loss statistically equal to the loss of those on the once-weekly 1 mg dose of injectable semaglutide. Now, because 14 mg is the highest dose currently prescribed for oral Rybelsus and 1 mg is the middle dose for Ozempic, this is where results could vary. 

The meta-analysis doesn’t dive deep into any studies that have measured the results of the 2 mg of Ozempic vs the 14 mg dose of oral Rybelsus, so it would truly be an equivalent comparison. And it would be helpful to get further information and clinical trials performed concurrently on the highest doses of both Rybelsus and Ozempic over a long period of time to see if the amount of weight loss stays comparable between the two.

What’s more, hemoglobin A1C (HbA1c) levels, which means the average blood sugar levels across the past two to three months, were similarly reduced when measuring the results of 14 mg of oral Rybelsus vs 1 mg of injectable Ozempic. So, with what we know, they seem to have meaningful results regardless of which form of med you take.

Ozempic vs Rybelsus: can you switch from one to the other?

You should be able to switch taking Rybelsus to Ozempic or vice versa, but please get medical advice and confirmation from your doctor. They must get your dosing schedule correct and help you seamlessly transfer from one to the other.

Some people decide that an oral pill may be easier than an injectable, so they switch. But again, ask your doctor or health care provider what’s best for you before moving forward with any med.

Rybelsus vs Ozempic: cost

Novo Nordisk is transparent about drug costs and lists prices for Rybelsus and Ozempic. 

As of May 2023, the Ozempic list price without insurance for all doses is $892.06 per 28-day supply. Similarly, the list price, without insurance, for Rybelsus is $851.60 per package for a 30-day supply. So, one of the differences between Rybelsus vs Ozempic is about $40. 

Novo Nordisk has a Savings Offer that includes Ozempic and Rybelsus. Some terms and conditions apply–you can read the full details here. A few to be aware of are that you need to be commercially insured, and a doctor must prescribe you Rybelsus or Ozempic for diabetes care. With the savings card, your co-pay could be as little as $10 monthly for Rybelsus and $25 per month for Ozempic.

What’s the verdict: Rybelsus or Ozempic?

In the Rebelsus vs Ozempic head-to-head comparison, the two meds are pretty similar. The big difference is that Rybelsus is an oral medication, while Ozempic is a subcutaneous (under-the-skin) injection. 

So if you think a GLP-1 receptor agonist is the right fit for you but want to start with a pill form, Rybelsus may be your way to go. On the other hand, if a weekly injection sounds like it would be perfect for you, then Ozempic could be for you.

Neither Rybelsus nor Ozempic is meant to treat those with type 1 diabetes. And let your doctor know about your full medical history, including any supplements or prescription drugs you’re taking and any medical conditions.

Also, other GLP-1 agonists like Victoza® (liraglutide), Wegovy® (semaglutide), and Trulicity® (dulaglutide) may be something to consider as you decide what med may be right for you.

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GLP-1*

GLP-1 prescriptions, filled through your local pharmacy, are now available as part of Found's weight-loss toolkit. While GLP-1s are effective for weight loss, they are not clinically appropriate for everyone. Eligibility for a GLP-1 is based on a thorough evaluation of your medical history, eating behavior, lab work, and insurance coverage. If a GLP-1 is not appropriate for you, our providers will work with you to determine an effective medication for your health profile.

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SOURCES

Chubb, B., Gupta, P., Gupta, J. et al. Once-Daily Oral Semaglutide Versus Injectable GLP-1 RAs in People with Type 2 Diabetes Inadequately Controlled on Basal Insulin: Systematic Review and Network Meta-analysis. Diabetes Ther 12, 1325–1339 (2021). https://link.springer.com/article/10.1007/s13300-021-01034-w#citeas

NovoMedLink. April 2023. Rybelsus Dosing and Prescribing. https://www.novomedlink.com/diabetes/products/treatments/rybelsus/dosing-administration/dosing-and-prescribing.html

NovoCare. Feb 2023. Find out the cost for Ozempic. https://www.novocare.com/diabetes/products/ozempic/explaining-list-price.html

NovoCare. Feb 2023. Find out the cost for Rybelsus. https://www.novocare.com/diabetes/products/rybelsus/explaining-list-price.html

Ozempic semaglutide injection. Oct. 2022. OZEMPIC® (semaglutide) injection, for subcutaneous use Initial U.S. Approval: 2017. Highlights of Prescribing information. https://www.novo-pi.com/ozempic.pdf

Ozempic. June 2022. How Ozempic works. https://www.ozempic.com/why-ozempic/how-ozempic-works.html

Rybelsus. April 2023. How Rybelsus works. https://www.rybelsus.com/why-rybelsus/how-rybelsus-works.html

Rybelsus. April 2023. What to expect with Rybelsus. https://www.rybelsus.com/taking-rybelsus/what-to-expect-with-rybelsus.html