People can’t stop talking about Ozempic, the buzziest diabetes and weight loss drug in memory. Ozempic is an injectable medication: users prick themselves with a pre-loaded syringe once per week. But while Ozempic is so popular that it’s led to shortages, there’s been hardly any hype for Rybelsus, an oral form of the exact same drug. Why aren’t people talking about Rybelsus? Is it just as good as Ozempic?
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.
Semaglutide is a GLP-1 receptor agonist, one of a family of drugs that mimic the effect of a hormone that stimulates insulin secretion and prompts feelings of hunger. Semaglutide was originally developed and approved to treat type 2 diabetes, but it turned out to be one of the greatest weight loss drugs ever invented. A high percentage of semaglutide users find themselves losing weight almost effortlessly — they simply eat less because they’re not as hungry anymore.
A third form of semaglutide, Wegovy, has been approved as a weight loss drug for people without diabetes.
Rybelsus is the only oral form of this powerful diabetes and weight loss medication. It has been shown to grant both weight loss and blood sugar improvements in many different populations, both alone and in combination with other diabetes drugs.
Is Rybelsus as Effective as Ozempic?
Rybelsus appears to be just as effective as Ozempic, but there’s a catch: Ozempic is available in more powerful doses.
To assess the potency of each drug, we can compare their results in studies that tested similar populations. According to the FDA (PDF), the maximum 14mg daily dose of Rybelsus is equivalent to the 0.5mg weekly dose of Ozempic — one can be switched for the other without the need for titration or adjustment.
(If you’re wondering why Rybelsus has so much more semaglutide in it than Ozempic, 14mg per day vs 0.5mg per week, it’s because only a tiny fraction of the semaglutide that enters the stomach is properly absorbed.)
The PIONEER 2 trial assessed Rybelsus’ efficacy for people with type 2 diabetes using metformin. After six months on the maximum dose, trial participants saw their average A1C drop 1.3 percentage points; after one year, they had lost about 10 pounds.
The SUSTAIN 2 trial assessed Ozempic in a similar population, people with type 2 diabetes using either metformin or a TZD. The 0.5mg dose of Ozempic conferred an A1C drop of 1.3 percentage points and a weight loss of 9.5 pounds. These extremely similar results suggest that the two drugs are equally effective.
But Ozempic is available in more powerful dosages. Ozempic’s maximum dose of 2.0mg, when tested in people with type 2 diabetes using metformin, led to a very impressive A1C drop of 2.2 percentage points, and weight loss of 15 pounds. Wegovy is available in an even higher dose, 2.4mg per week. Rybelsus can’t match these results — at least not at the approved doses — and it hasn’t yet been tested as a weight-loss medication for people without type 2 diabetes.
If there’s another reason that Rybelsus hasn’t caught on, it’s that taking the drug is kind of a hassle.
According to 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
By contrast, Ozempic is a single weekly injection and can be taken at any time of day, with or without meals.
Is a Higher Dose of Rybelsus on the Way?
Novo Nordisk is currently pushing for approval for a higher dose of Rybelsus.
How do we know that larger doses of Rybelsus will be more effective? Novo Nordisk recently announced the headline results of its PIONEER PLUS trial. This robust experiment tested larger doses of oral semaglutide, 25mg and 50mg per day. The trial ran for 68 weeks, with over 1,000 participants with type 2 diabetes. Here were the results:
|Dose||A1C Reduction||Weight Loss|
|14mg||1.5 percent||9.9 lbs|
|25mg||1.9 percent||15.4 lbs|
|50mg||2.2 percent||20.3 lbs|
The highest dose offered A1C and weight loss benefits on par with, or perhaps even better than, Ozempic’s current maximum dose of 2.0mg.
Novo Nordisk stated that it would apply for approval for these larger doses this year, although it’s difficult to guess when it may be available for patients.
Rybelsus and Side Effects
A substantial minority of Ozempic users experience gastrointestinal side effects. For some, the nausea, vomiting, or diarrhea subsides as their bodies acclimate to the powerful drug. But others are forced to quit the drug entirely.
Rybelsus has a pretty similar side effect profile. Here’s the number of people that experience belly troubles, according to the data that the FDA lists on its official labels for the two drugs at equivalent doses:
|Side Effect||Ozempic (%)||Rybelsus (%)|
As you can see, the numbers are very similar across the board.
The PIONEER PLUS trial did find that gastrointestinal side effects were more common with larger doses, though we don’t yet have the details on how much more common.
Rybelsus, like Ozempic, may carry a risk of other rare but serious side effects — please discuss this with your doctor.
Rybelsus, an oral form of semaglutide, appears to be just as powerful as Ozempic pound for pound, both for weight loss and diabetes management. However, it’s not quite as popular, likely for the following two reasons:
- Rybelsus is a hassle to take — it must be swallowed on an empty stomach, every morning, exactly 30 minutes before eating or drinking anything other than water, or using any other oral medications.
- Rybelsus is available in less powerful doses than Ozempic, which means less weight loss.
Despite these disadvantages, Rybelsus remains a very effective therapy for type 2 diabetes, granting both weight loss and glycemic improvement. It may be especially useful for people with needle phobia or those who cannot take Ozempic for any other reason.