Rybelsus for weight loss: does it work?

It seems like every day, there’s a new weight loss drug on the market or in the works. And some of these drugs—like Wegovy and Mounjaro—work so well that they’ve completely changed the game for millions of people (and will change the game for millions more) who’ve struggled for years to lose weight with diet and exercise alone.

However, there’s no such thing as a miracle drug that has no potential downsides and these medications are no exception. One complaint some people have is these medications require a weekly injection. The needle is very small, in some cases invisible, and relatively painless, but if you’re needle-squeamish, you may wonder: is there an oral alternative, a pill you can swallow instead of injecting yourself?

Yes, there is! Rybelsus is an oral medication with the same active ingredient as Wegovy (semaglutide). While research is limited on Rybelsus’s weight loss effects, it shows promise and may receive FDA-approval for this purpose in short order. Keep reading to learn what we know so far. 

Rybelsus is an oral form of semaglutide, a type of prescription medication called a GLP-1 agonist (glucagon-like peptide-1 receptor agonist). It’s approved by the US Food and Drug Administration (FDA) to be used alongside diet and exercise to help control blood sugar in people with type 2 diabetes mellitus. 

This diabetes medication can significantly lower hemoglobin A1C, a test that measures how much glucose is in the blood. People with type 2 diabetes develop insulin resistance, meaning ​​their body does not respond as it should to insulin, which regulates blood glucose. As the cells become more resistant to the hormone, the pancreas produces more insulin to overcome this resistance, but is often unable to keep up with the increased demand.

Rybelsus sends signals to the pancreas to produce more insulin, lowering blood sugar levels.

There are several other GLP-1s on the market—some, like Ozempic and Trulicity, are only approved for diabetes, while others, like Wegovy and Saxenda, are only approved for weight loss. Rybelsus is the only oral GLP-1 (all the others are injectable drugs), and as of now, it’s only being used for diabetes. 

Novo Nordisk, the manufacturer of Rybelsus, recently announced they’ve completed a 68-week clinical trial that shows oral semaglutide does indeed cause significant weight loss in those with obesity—at least when taken at high doses. 

We’ll talk about dosing in more detail further down in this article, but as a point of reference, typical dosing of Rybelsus ranges from 3 mg to 14 mg daily; the Novo Nordisk trial had participants on 50 mg of the drug. At that dose, participants lost over 17% of their initial body weight, on average.

What about the typical Rybelsus dosing for diabetes treatment?

One study showed that participants on the highest standard dose (14 mg) of oral semaglutide lost an average of 4.4 kg (less than 5% of their body weight) after 52 weeks. People who took a placebo only lost an average of 0.5 kg (0.5% of their body weight).

In other words, Rybelsus does result in weight loss, but the dose makes all the difference. 

Like other GLP-1 medications, Rybelsus delays gastric emptying, meaning it causes food to move more slowly through the digestive tract. This keeps you fuller for longer, decreasing appetite and resulting in weight loss.  

Another way it affects weight loss is by doing exactly what its drug class says it does: activating the GLP-1 receptor in the brain. GLP-1 is a natural hormone that does many things in the body, one of which is sending fullness signals to the brain after eating. The natural mechanism kicks into gear for only a few minutes, but taking a GLP-1 receptor agonist drug keeps that signal activated for much longer. 

Many people begin seeing modest weight loss within a week or so of starting Rybelsus. In the study we referenced above that showed an average weight loss of 4.4 kg, study participants saw modest, but steady weight loss until about week 26, after which their weight leveled off. 

The recent trial from Novo Nordisk that shows more significant weight loss on a higher dose of Rybelsus hasn’t yet been published as of June 2023, so the detailed data is not yet available.

It’s possible that results would be similar to those seen in injectable semaglutide. One trial on the highest dose approved for weight loss showed participants already saw an average of 2% weight loss by week 4 of the trial. They continued losing steadily until week 44, at which point their weight loss leveled off. 

Rybelsus has a list of possible side effects similar to other GLP-1s, including Ozempic. Since semaglutide affects digestion, the most common side effects are related to gastrointestinal issues. Common side effects of Rybelsus include: 

• Nausea

• Vomiting

• Abdominal pain

• Diarrhea

• Constipation

• Decreased appetite

Nausea is the most common of these, impacting up to 20% of people taking 14 mg daily. Still, most are able to tolerate the medication well; according to the medication label, about 8% of people taking the higher dose of Rybelsus stopped the medication because of the side effects. That may sound like a lot, but 92% of people tolerate the side effects enough to stay on it.

It’s important to note that with most medications, including Rybelsus, side effects tend to be the worst when you first start taking it and usually get better with time.

It’s safe to use Rybelsus with most medications, but since it slows down digestion, it can affect how the body absorbs other oral medications. In particular, this effect has been noted in people taking Synthroid (levothyroxine), a drug used to treat an underactive thyroid. 

This doesn’t mean you can’t take Rybelsus and Synthroid together, but you may need additional monitoring to ensure you’re getting the full effects of all your medications. 

Because Rybelsus is so effective at lowering blood glucose levels in people with type 2 diabetes, it may cause hypoglycemia if you combine it with other medications that lower blood sugar. For instance, if you’re taking insulin, you and your healthcare provider need to watch out for low blood sugar and maybe adjust the insulin dose.

Like other GLP-1s, Rybelsus comes with a black box warning (the FDA’s strongest warning) that it should not be taken if you have a personal or family history of MTC (medullary thyroid carcinoma, a specific type of thyroid cancer) or MEN2 (multiple endocrine neoplasia syndrome type 2, a rare, hereditary cancer condition). Studies on mice have shown an increased risk of MTC with Rybelsus, though these effects have not been seen in humans.

Other rare, serious side effects to be aware of include an increased risk of:

• Diabetic retinopathy

• Pancreatitis

• Acute kidney injury

• Allergic reaction

Rybelsus can be pretty pricey without insurance coverage. Semaglutide, the active ingredient in Rybelsus, Ozempic, and Wegovy, is not currently available as a generic medication, and these brand-name versions are all costly.

The average retail (out-of-pocket) cost for Rybelsus is around $1,000 per month, with some differences between pharmacies (so it’s worth shopping around a bit).

Websites like GoodRx offer coupons that can help you save money. Novo Nordisk also offers a savings program if you’re eligible. 

Your insurance may cover Rybelsus. You can call your insurance provider to find out if Rybelsus or oral semaglutide are covered under your prescription drug plan. Your healthcare provider’s office may be able to help with insurance verification, too.

Rybelsus is available in three doses: 3 mg, 7 mg, and 14 mg. 

As mentioned, the weight loss effects of Rybelsus, even at the highest approved dose, are quite modest. At higher doses, though, it shows promise as a potential weight loss drug. Novo Nordisk is currently studying it at 25 mg and 50 mg doses, and the evidence we have so far paints a pretty clear picture: higher doses lead to more weight loss. 

Novo Nordisk announced that they plan to submit Rybelsus for approval as a weight loss drug, but it will still be some time before that comes to pass. In the meantime, most providers are prescribing other medications for weight loss, including injectable GLP-1 drugs, both on-label and off-label for weight management. 

For people who hate needles, the idea of an oral medication that does the same thing as injectable GLP-1s probably sounds like a dream come true. Unfortunately, Rybelsus isn’t yet approved for weight loss, and most providers won’t be willing to prescribe it at the doses necessary to see significant weight loss. 

The good news is plenty of options on the market that can help you lose weight, alongside your efforts at diet and exercise.

While some of these alternatives require a needle, the needle is tiny, hidden inside a plastic pen, and gets injected subcutaneously (meaning, just below the skin), so most people barely feel it.

There are two GLP-1 medications currently approved for weight loss: Wegovy (semaglutide) and Saxenda (liraglutide).

Other GLP-1 drugs are, like Rybelsus, only approved for treating type 2 diabetes, but many providers will prescribe them off-label for weight loss. These include Ozempic (semaglutide), Trulicity (dulaglutide), and Victoza (liraglutide), among others.

Mounjaro (tirzepatide) is another drug that’s often prescribed off-label for weight loss, but is in the process of getting approval for that purpose. It’s a dual drug that acts on GLP-1 and another hormone called GIP. 

Other oral weight loss medications

While Rybelsus is the only oral GLP-1 available, other oral medications are FDA-approved for weight loss. These include:

• Qsymia (phentermine/topiramate) 

• Contrave (naltrexone/bupropion)

• Xenical, Alli (orlistat)

Rybelsus and Ozempic share the same active ingredient and are both highly effective diabetes drugs. When it comes to controlling blood sugar, oral Rybelsus seems to perform better than its injectable counterpart, Ozempic, but the results are dose-dependent.  

When it comes to weight loss, at their approved doses, Ozempic leads to more weight loss. At higher doses currently being studied, though, Rybelsus may outperform Ozempic. 

Time will tell if Rybelsus gets approval at higher doses for weight loss, but for now, many options are available. Losing weight is complicated, and lifestyle interventions alone are not enough for many people. Thankfully, many medications are available now to bolster those efforts and help you reach your goals. Speak with your healthcare provider to find out which option is best for you.

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Current version

June 08, 2023

Written by

Rachel Honeyman

Fact checked by

Felix Gussone, MD

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About the medical reviewer

Felix Gussone, MD, Ro

Felix Gussone is a physician, health journalist and a Manager, Medical Content & Education at Ro.