This content originally appeared here. Republished with permission.
Medically Reviewed by Sean Hashmi, MD
People can’t stop talking about semaglutide (Ozempic, Wegovy), the buzzy diabetes and weight loss drug. Ozempic and Wegovy are injectable medications: Users prick themselves with a preloaded syringe once per week. But while the popularity of Ozempic has led to shortages, there’s been much less hype for Rybelsus, an oral form of semaglutide — the exact same drug.
What Is Rybelsus?
Rybelsus is essentially Ozempic in the form of a pill rather than an injection. Ozempic and Rybelsus are made by the same manufacturer, Novo Nordisk, and have the same active ingredient, semaglutide.[1] Semaglutide, when sold under the brand name Ozempic, is intended for people with type 2 diabetes. The same drug is also sold as Wegovy for the treatment of obesity.
Semaglutide is a GLP-1 receptor agonist, a type of drug that mimics the effect of a hormone that stimulates insulin secretion and prompts feelings of fullness. Semaglutide was originally developed and approved to treat type 2 diabetes, and it remains a powerful glucose-lowering therapy, it also has a profound effect on body weight. Many semaglutide users find themselves losing weight without having to consciously cut calories.[2]
Rybelsus is the only approved oral form of semaglutide. It’s a daily pill, and it has been shown to result in clinically significant weight loss and blood sugar improvements, both alone and in combination with other diabetes drugs.[3]
Is Rybelsus as Effective as Ozempic?
Rybelsus appears to be just as potent as Ozempic, but there’s a catch: It is only available in smaller doses.
According to the U.S. Food and Drug Administration (FDA), the maximum 14 milligram (mg) daily dose of Rybelsus is equivalent to the 0.5 mg weekly starter dose of Ozempic — one can be switched for the other without the need for a dose adjustment.[4] (Rybelsus uses higher amounts of semaglutide than Ozempic, because only a fraction of the semaglutide that enters the stomach is properly absorbed.)[5]
Clinical trials show that the two doses have a comparable metabolic effect: [6]
| Rybelsus 14 mg daily pill | Ozempic 0.5 mg weekly injection |
|---|---|
| 1.3 percentage point drop in A1C | 1.3 percentage point drop in A1C |
| 10 pounds weight loss | 9.5 pounds weight loss |
A study of real-world data found similar results: Oral semaglutide demonstrated “similar effectiveness” to injectable semaglutide.[7]
While these results suggest that Rybelsus and Ozempic could be similarly effective for people with type 2 diabetes, the two drugs are not equivalent, practically speaking, because Ozempic is available in more powerful dosages.
Ozempic is additionally available in 1 and 2 mg doses. The maximum dose, when tested in people with type 2 diabetes using metformin, led to an A1C drop of 2.2 percentage points, and weight loss of 15 pounds.[8] Rybelsus can’t match these results — at least not at the approved doses. Wegovy is available in an even higher dose, 2.4 mg per week.
Higher Doses of Rybelsus Are On The Way
In the coming years, higher doses of Rybelsus may become available. In 2023, Novo Nordisk announced that it would seek FDA approval for larger doses of oral semaglutide for the treatment of type 2 diabetes.[9]
The PIONEER PLUS trial, which tested two experimental larger doses of oral semaglutide in people with type 2 diabetes, demonstrated that at the highest dose of 50 mg, the drug’s glucose-lowering and weight loss results were at least as good as those found in Ozempic 2 mg. Study participants had an A1C reduction of 2 percentage points, and weight loss of about 20 pounds.[10][11]
Is Rybelsus Approved for Weight Loss?
Oral semaglutide is not yet approved as a weight loss therapy.
In the recent OASIS 1 trial, however, researchers tested the effect of a 50 mg dose of oral semaglutide for people who were overweight or had obesity.[12] After using the drug for over one year, study participants lost an average of 15.1 percent of their total body weight. That amount of weight loss was about equal to that achieved by people using the maximum dose of injectable semaglutide, suggesting that an oral semaglutide weight loss pill could be just as effective as the injectable.[13]
Novo Nordisk has already applied for regulatory approval for a semaglutide weight loss pill in both the United States and Europe.[14]
In the meantime, some doctors are prescribing Rybelsus off-label as a weight loss therapy for people without diabetes, especially those who cannot tolerate Wegovy or who are unable to use needles.
How to Take Rybelsus
If there’s another reason that Rybelsus hasn’t quite caught on, it’s that taking the drug is arguably something of a hassle.
According to the instructions on the FDA label, you need to take Rybelsus on an empty stomach, every morning, 30 minutes before eating, drinking, or using any other oral medications. You may have up to 4 ounces of plain water only during this time. If you have your breakfast too early, the pill will be less effective. But if you wait longer than 30 minutes to eat, the pill’s absorption may be enhanced (which could also lead to more significant side effects).
By contrast, Ozempic is a single weekly injection and can be taken at any time of day, with or without meals.
Rybelsus and Side Effects
A substantial minority of Ozempic users experience gastrointestinal side effects.[15] For some, the nausea, vomiting, or diarrhea subsides as the body gets acclimated to the drug. But others don’t feel better and end up quitting the drug entirely.
Clinical trials suggest that Rybelsus has similar side effects. A roughly similar proportion of Rybelsus study participants reported experiencing the most common side effects, including nausea, abdominal pain, diarrhea, and vomiting.
Rybelsus’ FDA label also warns of some of the same rare, serious side effects as Ozempic, including pancreatitis (inflammation of the pancreas) and acute kidney injury (a sudden decrease in kidney function).[4]
Compounded Oral Semaglutide
Some online compounding pharmacies are now advertising “oral semaglutide,” but some of these products are not, in fact, equivalent to Rybelsus. These semaglutide pills are taken sublingually (dissolved under the tongue) rather than swallowed, and therefore have an entirely different mechanism for absorption.
Buyers should be wary of such products, as there has never been any published study of sublingual semaglutide, and the safety and efficacy of such substances may be questionable.
The Takeaway
Rybelsus, an oral form of semaglutide, appears to be just as effective as Ozempic and Wegovy for diabetes management and weight loss, but it is only available in less powerful doses. In the coming years, larger doses for the treatment of both diabetes and obesity may become available. In the meantime, Rybelsus remains an effective therapy for type 2 diabetes, and may be especially useful for people with needle phobia or those who cannot take Ozempic for any other reason.
