When comparing the medications Rybelsus vs. Ozempic, they have a lot in common. They’re both prescription GLP-1 medications with semaglutide as their active ingredient. They’ve both been approved by the FDA to help treat type 2 diabetes. They both work in the body in much the same way: increasing how much insulin is released to regulate blood sugar levels and slowing down digestion to help you feel full for longer. But Rybelsus and Ozempic also have some important differences, especially in dosing and administration. If you’re considering taking semaglutide for your type 2 diabetes and aren’t sure which version is best for you, here’s what you should know.
What is Rybelsus?
Rybelsus is a prescription glucagon-like peptide-1 (GLP-1) receptor agonist with the active ingredient semaglutide. It’s manufactured by Novo Nordisk and was approved by the FDA in 2019 to treat type 2 diabetes in adults when paired with diet and exercise. Unlike other GLP-1s which are injectable medications, Rybelsus is an oral tablet you take once a day.
Semaglutide and other GLP-1 medications work by mimicking the action of the hormone GLP-1 to regulate insulin secretion and control blood sugar. Rybelsus increases the amount of insulin that’s released from the pancreas after you eat and prevents the liver from releasing stored sugar into the bloodstream. It also slows down gastric emptying and suppresses appetite.
What is Ozempic?
Like Rybelsus, Ozempic is a prescription semaglutide GLP-1 medication manufactured by Novo Nordisk. It’s also FDA approved to treat type 2 diabetes and should be paired with diet and exercise. It mimics that same GLP-1 hormone to stimulate insulin production, suppress appetite, and slow gastric emptying as a way to regulate blood sugar. Unlike Rybelsus, Ozempic is an injectable liquid that comes in a prefilled auto-injector pen. On an Ozempic prescription, you give yourself the injection subcutaneously (just under the skin) once a week.
While Ozempic was approved by the FDA in 2017 for type 2 diabetes, it was approved in 2020 to reduce the risk of major adverse cardiovascular events (like heart attacks and strokes) in adults with type 2 diabetes and known heart disease. And in 2025 it was approved to reduce the risk of kidney disease, kidney failure, and cardiovascular-related death in adults with type 2 diabetes and chronic kidney disease.
Key differences between Ozempic and Rybelsus
Here’s how the two medications stack up against each other.
- FDA approvals: Rybelsus and Ozempic are both approved to treat type 2 diabetes, but Ozempic is also approved to reduce the risk of cardiovascular events, kidney disease, and kidney failure in certain people.
- Format: Ozempic is an injectable liquid while Rybelsus is an oral tablet.
- Frequency You give yourself the Ozempic injection once a week, while Rybelsus is taken every day.
- How you take it: Ozempic can be injected with or without food. Rybelsus is taken in the morning on an empty stomach with less than four ounces of water.
Rybelsus vs. Ozempic uses
Both medications are used to treat type 2 diabetes alongside a healthy diet and regular exercise. Ozempic has two other approved uses: to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes and known heart disease and to reduce the risk of kidney disease, kidney failure, and cardiovascular-related death in adults with type 2 diabetes and chronic kidney disease.
Because semaglutide reduces your appetite, people taking Ozempic and Rybelsus often report weight loss. That said, these two drugs are not approved by the FDA for that purpose. Wegovy is the brand name of semaglutide that’s FDA approved for weight loss.
Rybelsus vs. Ozempic dosages and administration
These two medications have different dosage levels — Ozempic is available in 0.25 mg, 0.5 mg, 1 mg, or 2 mg doses and Rybelsus comes in 3 mg, 7 mg, or 14 mg doses.
Why are Ozempic doses smaller? Because it’s an injection while Rybelsus is a pill, so they’re absorbed by the body very differently, says Dr. Dyan Hes, M.D., an obesity-medicine specialist, diplomate of the American Board of Obesity Medicine, pediatrician and medical director at Highline Modern Medicine in New York City. “When you're getting Rybelsus, you have gastrointestinal absorption, and when you're getting Ozempic, it’s going directly into the bloodstream and is bypassing the gastrointestinal system,” Hes says. That trip the pill takes through the GI tract affects the absorption of the medication, since digestive enzymes degrade the drug before it can circulate through your body.
Whether you’re taking Ozempic or Rybelsus, you’ll likely start on the lowest dose and work your way up. So on Rybelsus, patients typically start with 3 mg and may increase to 7 mg or 14 mg, says Dr. Nicole Ehrhardt, M.D., a board-certified endocrinologist specializing in diabetes and assistant professor of medicine at University of Washington Medicine Diabetes Institute. On Ozempic, you’d start at 0.25 mg and then work up to 0.5 mg, 1 mg, or 2 mg, as needed.
Ozempic is injected into the upper arm, upper thigh, or stomach. It can be taken with or without food, any time of day. Rybelsus has stricter usage directions. To get the full effect of the medication, Rybelsus must be taken in the morning on an empty stomach. You take it with a sip of plain water — no more than 4 ounces — and wait 30 minutes before eating, drinking, or taking other oral medications, vitamins, or supplements, Ehrhardt says.
This might sound super specific, but it’s important to follow those directions. “Absorption can be greatly affected by variables such as food intake and timing,” says Dr. Christopher McGowan, M.D., a board-certified gastroenterologist and obesity medicine physician and CEO of True You Weight Loss in Cary, North Carolina. “Patients have to take it as directed.”
Effectiveness of Rybelsus vs. Ozempic
Clinical trials have found both medications are effective at treating type 2 diabetes and lowering A1c levels, which measures average blood sugar over a three-month period. Research suggests Ozempic may have a stronger impact on A1c than Rybelsus. With Ozempic, people’s A1c levels dropped an average of 1.9% with the 1 mg dose and 2.1% with the 2 mg dose. On Rybelsus, the average reduction in A1c is 1.3% on the maximum 14 mg dose.
Weight loss, which can happen with both medications, also will likely be greater with Ozempic than Rybelsus. “I tend to use Rybelsus when I do not want as much weight loss in patients but still want a good diabetes medication,” Ehrhardt says. “However, I use it less in my practice than Ozempic, given you get more weight loss and more glucose lowering with Ozempic. And once people see how easy the [Ozempic] injection is, they tend to lean toward using it.”
Rybelsus vs. Ozempic cost and insurance coverage
Novo Nordisk, which manufactures both medications, prices Rybelsus and Ozempic the same: $997.58 per month. That would be what you’d pay without any insurance coverage or savings plans. Whether they are covered by your insurance depends on your plan. “Coverage will vary greatly by insurance plan, and that's likely to dictate the choice of one over the other,” McGowan says. But he adds that Ozempic, Rybelsus, and other GLP-1 medications for type 2 diabetes tend to be covered more regularly than GLP-1s approved for weight loss, such as Wegovy. For example, both Medicare and Medicaid cover type 2 diabetes medications like Ozempic and Rybelsus.
There are other ways to bring the cost of Ozempic and Rybelsus down. Novo Nordisk offers a savings plan in which eligible patients can get Rybelsus for as little as $10 per month. Ozempic also has a savings plan for people with public or private insurance, in which they can pay as little as $25 for a one-, two-, or three-month supply for up to 48 months. And if you live in a low-income household with Medicare or no insurance, Novo Nordisk also has a Patient Assistance Program to lower costs as well.
Rybelsus vs. Ozempic side effects
As would be expected when comparing two medications with the same active ingredient, Rybelsus and Ozempic have very similar side effects, with gastrointestinal problems being the most common for both.
Clinical trials have found more Rybelsus users experienced the most common GI side effects, although nausea occurred more frequently in Ozempic users. “The digestive side effects may be more frequent with Rybelsus because it's delivered through the stomach,” McGowan says.
Serious side effects for Rybelsus and Ozempic are rare, but include pancreatitis (inflammation of the pancreas), vision changes, severe stomach problems, gallbladder problems, and severe allergic reactions. Let your provider know about any side effects so they can adjust your dosage or recommend treatment if necessary.
Rybelsus side effects
Common side effects of Rybelsus are:
- Nausea: 11% of people experienced this on the 7 mg dose and 20% on the 14 mg dose, compared to 6% with a placebo
- Diarrhea: 9% (7 mg) and 10% (14 mg), compared to 4% with a placebo
- Vomiting: 6% (7 mg) and 9% (14 mg), compared to 3% with a placebo
- Constipation: 6% (7 mg) and 5% (14 mg), compared to 2% on a placebo
- Decreased appetite: 6% (7 mg) and 9% (14 mg), compared to 1% on a placebo
- Abdominal pain: 10% (7 mg) and 11% (14 mg), compared to 4% on a placebo
Ozempic side effects
Ozempic side effects are generally similar to the common ones seen with Rybelsus:
- Nausea: 15.8% of people experienced this on the 0.5 mg dose and 20.3% on the 1 mg dose, compared to 6.1% on a placebo
- Diarrhea: 8.5% (0.5 mg) and 8.8% (1 mg), compared to 1.9% on a placebo
- Vomiting: 5.0% (0.5 mg) and 9.2% (1 mg), compared to 2.3% on a placebo
- Constipation: 5.0% (0.5 mg) and 3.1% (1 mg), compared to 1.5% on a placebo
- Abdominal pain: 7.3% (0.5 mg) and 3.1% (1 mg), compared to 4.6% on a placebo
Unlike Rybelsus, “Ozempic may also cause injection site reactions, which would be unique to that delivery mechanism,” McGowan says.
Rybelsus and Ozempic drug warnings
Both medications carry a “black box” warning, which is the most serious warning the FDA puts on medication packages, about an increased risk of developing possibly cancerous thyroid tumors. This warning is based on clinical trials on rats, but the same link has not been found in human trials. And recent research by the American Thyroid Association has found no association between the use of GLP-1 drugs and an increased risk of thyroid cancer in humans.
The bottom line
Rybelsus and Ozempic are two GLP-1 medications with semaglutide as the active ingredient. Both have been approved by the FDA to treat type 2 diabetes while Ozempic is also approved to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes and known heart disease and to reduce the risk of kidney disease, kidney failure, and cardiovascular-related death in adults with type 2 diabetes and chronic kidney disease. Rybelsus is a pill that’s taken orally once a day and it must be taken in the morning on an empty stomach and with just a sip of water. Ozempic is an injectable medication that’s administered once a week. Clinical trials have shown Ozempic to be slightly more effective in lowering A1c than Rybelsus. Both medications have similar side effects, carry the same drug warnings, and cost the same out of pocket.
FAQs
Both are clinically proven effective treatments for type 2 diabetes, but Ozempic has been shown to lower A1c levels more than Rybelsus. Which drug you take is largely a matter of personal preference, Hes says. If needles or self-injections make you uncomfortable, or if you travel a lot and find it hard to keep Ozempic refrigerated, Rybelsus might be a better fit. If you like the convenience of taking medication once a week instead of once a day, you might prefer Ozempic.
Rybelsus is indicated for use as a treatment for type 2 diabetes, along with diet and exercise. Prescribing it for any other reason is up to the discretion of your provider.
Availability can vary between different pharmacies and providers. While Ozempic and other forms of semaglutide have gone on and off the FDA drug shortage list, Rybelsus has remained available. If you find it hard to get, it could be that your provider is not as familiar with Rybelsus as they are with Ozempic, so doesn’t prescribe it as often, Hes says.
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This content is for informational purposes only and does not constitute medical advice, diagnosis or treatment. It should not be regarded as a substitute for guidance from your healthcare provider.