Rybelsus vs. Ozempic: which semaglutide is right for you?

Rybelsus and Ozempic are two different forms of the same GLP-1 (glucagon-like-peptide-1) medication with the active ingredient, semaglutide. Both medications are approved for adults with type 2 type 2 diabetes.

Rybelsus is a daily oral tablet, and Ozempic is a weekly injection. Both work the same way in the body to manage blood sugar levels, but the choice between the two depends on personal preference and how your body reacts to the medication. Ozempic has shown better results with weight loss and blood sugar control in clinical trials. Rybelsus may be a preferred option if you don’t want to take injections.

Rybelsus vs Ozempic: Which is better for you? Learn how these semaglutide medications compare for type 2 diabetes, dosage, administration, and side effects, including their key similarities and differences.

What are Rybelsus and Ozempic?

Rybelsus and Ozempic are prescription drugs containing the same active ingredient, semaglutide, approved by the FDA (U.S. Food and Drug Administration) to help lower blood sugar levels in adults with type 2 diabetes. Both medications are manufactured by Novo Nordisk.

Semaglutide belongs to a class of drugs called glucagon-like peptide-1 (GLP-1) receptor agonists and is known for its dual benefits: it helps control blood glucose levels in adults with type 2 diabetes and supports weight loss in people with or without diabetes (off-label) when used in combination with diet and increased physical activity.

Semaglutide works for weight loss by mimicking the action of incretin, a natural gut hormone called GLP-1, and targeting GLP-1 receptors in the brain that control appetite and slow down how quickly the stomach empties, making you feel fuller for longer. By increasing GLP-1 activity, semaglutide helps to reduce hunger and suppress appetite.

Ozempic is an FDA-approved medication used to lower blood sugar in people with type 2 diabetes and also used off-label for weight loss in people with obesity and overweight.

Ozempic is also FDA-approved for reducing the risk of major cardiovascular events (heart attack, stroke) in adults with type 2 diabetes and known heart disease and for reducing the risk of worsening kidney disease and cardiovascular death in adults with chronic kidney disease and type 2 diabetes.

Rybelsus is an oral tablet that is FDA-approved for lowering blood sugar levels in adults with type 2 diabetes and may also help with weight loss. Although it’s not FDA-approved to reduce the risk of heart attack or stroke, studies suggest it’s safe for people with heart disease. It’s taken daily at least 30 minutes before eating or drinking. The tablets should be swallowed whole and cannot be crushed, split or chewed.

Ozempic is an injection that is administered under the skin of the stomach, upper thigh or arm. It’s injected once weekly with or without food. It’s commonly prescribed off-label for weight loss, and there’s another medication called Wegovy, which contains the same active ingredient, semaglutide, and is FDA-approved for chronic weight management.

Similarities between Rybelsus and Ozempic

Rybelsus and Ozempic are both GL-1 medications and have many similarities:

• Active ingredient: Both contain the active ingredient semaglutide, a GLP-1 receptor agonist.
• FDA approvals: Both are FDA-approved to control blood sugar in adults with type 2 diabetes.
• Mechanism of action: Both mimic a natural hormone in your body called GLP-1, increase insulin, decrease glucagon to prevent liver sugar production, slow gastric emptying, and target GLP-1 receptors in the brain to reduce appetite and increase feelings of fullness.
• Effectiveness: Both work to lower blood sugar when used with diet and exercise.
• Weight loss: Both can lead to weight loss as a secondary benefit.

Active ingredient

Both Rybelsus and Ozempic have the same active ingredient, semaglutide. Semaglutide works by increasing insulin and decreasing glucagon to control blood sugar in adults with type 2 diabetes. Despite being different forms, Rybelsus oral tablet and Ozempic injection, the active ingredient is the same and both medications are effective for diabetes.

Mechanism of action

Both Rybelsus and Ozempic lower blood sugar by mimicking a natural hormone called GLP-1 that your body makes after you eat. This helps your body release insulin and reduce sugar production, providing more effective blood sugar control.

At the same time, these medications reduce the amount of glucagon, a hormone that signals the liver to release sugar, preventing excessive sugar production. By enhancing insulin secretion and reducing sugar release from the liver, both medications help improve overall blood sugar control.

They help with weight loss by reducing appetite, slowing down digestion (gastroparesis), and targeting GLP-1 receptors in the brain to reduce appetite and make you feel fuller longer.

Benefits for type 2 diabetes

Rybelsus and Ozempic are both prescription medications containing the same active ingredient, semaglutide. Both medications can:

• Help improve blood sugar control and lower A1c levels, a key marker of blood sugar control
• Aid in weight loss, although Ozempic may be more effective for this benefit
• Reduce the risk of cardiovascular events, such as heart attacks and strokes, in people with type 2 diabetes

Common side effects

The common side effects of Rybelsus and Ozempic include:

• Nausea
• Vomiting
• Diarrhea
• Constipation
• Abdominal pain
• Decreased appetite

These side effects are generally mild and tend to lessen over time as your body adjusts to the medication. However, if they persist or become severe, it’s important to consult your healthcare provider.

Serious side effects

Although rare, some people taking Rybelsus or Ozempic may experience:

• Severe allergic reaction
• Kidney problems
• Gallbladder problems
• Low blood sugar (hypoglycemia)
• Pancreatitis (inflammation of the pancreas)
• Diabetic retinopathy in patients with Type 2 Diabetes
• Thyroid tumors, including medullary thyroid carcinoma, a rare but serious condition

Warnings

Both drugs have a black box warning from the FDA for the risk of thyroid tumors or thyroid cancer. They must not be given to people with a personal or family history of multiple endocrine neoplasia syndrome type 2 (MEN 2) or medullary thyroid carcinoma (MTC).

You should not use Rybelsus or Ozempic if you:

• Are allergic to semaglutide or any of the ingredients.
• Are pregnant or planning to become pregnant.
• Are breastfeeding.
• Have serious kidney or liver problems.
• Have a severe gastrointestinal disease, such as gastroparesis (delayed stomach emptying).

Key differences between Rybelsus and Ozempic

Rybelsus and Ozempic (semaglutide) are both popular medications for type 2 diabetes. They work in similar ways, but there are some key differences between them.

FDA-approved uses

Both Rybelsus and Ozempic are FDA-approved for managing type 2 diabetes. While both medications also help with weight loss, they are not FDA-approved for chronic weight management. Wegovy is a brand-name weight loss drug containing the same active ingredient as Rybelsus and Ozempic.

Rybelsus is FDA-approved for:

• Improving blood sugar control in adults with type 2 diabetes mellitus, alongside diet and exercise

Although not FDA-approved for weight management, Rybelsus also helps in weight loss (as an additional benefit) in people with type 2 diabetes, especially when diet and exercise alone do not provide sufficient control.

Rybelsus is currently being studied in a long-term trial to confirm its potential cardiovascular benefits.

Rybelsus is not approved for the treatment of type 1 diabetes or diabetic ketoacidosis.

Ozempic is FDA-approved for:

• Controlling blood sugar in adults with type 2 diabetes
• Reducing the risk of serious heart problems, like heart attack, stroke, and death, in adults with type 2 diabetes and heart disease
• Reducing the risk of worsening kidney disease and cardiovascular deaths in adults with type 2 diabetes and chronic kidney disease.

Although Ozempic isn’t FDA-approved for weight loss, a healthcare provider may prescribe it off-label to help with weight management. Alternatively, your healthcare provider may prescribe Wegovy, which is FDA-approved for chronic weight management and contains the same active ingredient as Ozempic.

Administration

Rybelsus is an oral tablet that you take once a day by mouth on an empty stomach at least 30 minutes before eating or drinking. This makes it convenient for those who prefer not to use injections. The tablet should be swallowed whole with water (about 4 ounces). After taking Rybelsus, it is important to wait at least 30 minutes before eating, drinking, or taking any other medications to ensure proper absorption of the medication for maximum effectiveness.

Ozempic is an injectable solution administered once weekly under the skin (subcutaneously) of your stomach, upper arm, or thigh. It can be taken with or without food. Ozempic injection pens have more than one dose, so you’ll need to put on a new needle each time you inject and set your dose. Unopened pens should be kept in the fridge until their expiration date, and opened pens can be stored at room temperature or in the fridge for up to 56 days.

While both medications contain the same active ingredient, semaglutide, their different forms of administration offer flexibility depending on a person’s preference for daily versus weekly dosing and tablet versus injection form.

Dosage strengths

Although Rybelsus and Ozempic have the same active ingredient, semaglutide, they come in different dosage forms. Rybelsus is taken as an oral tablet, while Ozempic is administered as an injection.

Rybelsus comes as an oral tablet in three doses: 3 mg, 7 mg, and 14 mg. The tablet should be stored in its original container because it’s sensitive to moisture, heat, and light. Your healthcare provider will determine the right dose based on your needs and how you respond to the medication. Typically, treatment starts with a lower dose and may be increased gradually.

Ozempic comes as a prefilled multi-dose pen in four doses: 0.25 mg (starting dose), 0.5 mg, 1 mg, and 2 mg (maximum dose). As the pens are multi-dose, you can reuse the pen for a month but use a new needle each time. Your pharmacy will give you one pen and the needles.

Onset of action

Rybelsus and Ozempic both start working quickly, but there are some differences in how fast they take effect and reach their full impact.

As Rybelsus is absorbed through the digestive tract, it takes 1 to 2 hours for maximum concentration after taking the medication, and could take at least 4 to 5 weeks or possibly months of continued daily use for Rybelsus to build up to its maximum effectiveness in the body.

As Ozempic is injected directly into the bloodstream, it takes 1 to 3 days for maximum concentration after taking the medication, and could take at least 4 to 5 weeks of weekly injections to reach steady-state levels in the body.

The pronounced effects of both medications are typically seen over the long term as the dosage is increased gradually.

Side effects

As Rybelsus and Ozempic both contain the same active ingredient, semaglutide, their side effects are very similar. Side effects are most common when you first start using the medication or increase the dose, and higher doses of both drugs can lead to a higher risk of side effects.

The most common side effects of Rybelsus include:

• Nausea
• Diarrhea
• Vomiting
• Constipation
• Abdominal pain
• Decreased appetite

The most common side effects of Ozempic include:

• Nausea
• Vomiting
• Diarrhea
• Loss of appetite
• Constipation
• Stomach pain

Effectiveness for blood sugar control and reducing hemoglobin a1c levels

Both Rybelsus and Ozempic are effective at reducing HbA1c levels, a key marker for blood sugar control in people with type 2 diabetes. However, Ozempic tends to be more effective in lowering HbA1c.

Ozempic can reduce HbA1c by about 1% to 1.5%, while Rybelsus typically reduces it by around 0.8% to 1%. The difference may be because Ozempic is injected weekly, providing more consistent control, while dose of Rybelsus is once daily.

Effectiveness for weight loss

Rybelsus and Ozempic aren’t approved for weight loss, but many people do lose weight while taking them.

A study showed that both medications led to similar weight loss, around 5 to 6 kg after 6 months. Ozempic also comes in a 2 mg dose, but the weight loss difference between the 1 mg and 2 mg doses is not significant.

In a clinical trial, people taking 14 mg of Rybelsus once a day lost an average of 3.6 kg after one year. In comparison, those who took a placebo (a non-active pill) gained 0.5 kg during the 52-week trial.

Both Rybelsus and Ozempic can work for weight loss and your healthcare provider can help you decide which one is best for you.

Cost and insurance coverage

Ozempic and Rybelsus are only available as brand-name medications. There are currently no generic alternatives available for either medication. The cost of Rybelsus and Ozempic varies based on your dose, insurance coverage, and whether you qualify for the manufacturer’s savings card program or patient assistance program.

Eligible patients can receive free Ozempic or Rybelsus through the Novo Nordisk Patient Assistance Program (PAP). This program helps uninsured or underinsured patients access the medication for free if they meet certain criteria. Patients generally need to meet income and insurance criteria to qualify. However, the program is only for people with type 2 diabetes and not for weight loss.

Most insurance plans cover Rybelsus and Ozempic for type 2 diabetes, but coverage for weight loss alone is unlikely, especially with Medicare and Medicaid plans. How much you pay with insurance depends on your specific insurance plan, drug tier, and deductible. Contact your insurance provider for coverage details to find out if they cover Rybelsus or Ozempic and find out the associated out-of-pocket costs.

The cost of Rybelsus and Ozempic can vary depending on your pharmacy and insurance coverage.

Without insurance, a 30-day supply of Rybelsus costs about $997.58. If you’re eligible, you could pay $10 for Rybelsus  (1-month supply) with a copay savings card from the manufacturer. The Rybelsus Savings Card program is limited to those with commercial insurance.

Ozempic costs around $997.58 for a 28-day supply without insurance. The Ozempic Savings Card program can reduce the cost of Ozempic to as low as $25 per month if you have commercial insurance.

Rybelsus vs. Ozempic: Key differences

Rybelsus vs. Ozempic: which is right for you?

Choosing between Rybelsus and Ozempic is a personal decision you should make with your doctor. Both medications are effective for blood sugar and weight loss. Here are some things to consider:

• Personal preference: Rybelsus vs. Ozempic depends on your personal preferences and lifestyle. Rybelsus is a once daily oral tablet so it may be better for you if you don’t want to take injections. It needs to be taken on an empty stomach, which can be inconvenient for some people. Ozempic is once a once-a-week injection so it may be better for you if you don’t mind injections and prefer weekly injections instead of daily tablets.
• Medical conditions: If you have gastroparesis, Rybelsus might not be the best option, as it could make it worse. Both should be avoided if you have thyroid cancer or multiple endocrine neoplasia type 2. If you have heart disease or chronic kidney disease, Ozempic may be a better option for you.
• Effectiveness: Both Rybelsus and Ozempic are effective for blood sugar control in type 2 diabetes. However, some studies show Ozempic might be better for weight loss and blood sugar control than Rybelsus. This could be because of Ozempic’s injectable administration.
• Side effects: Your tolerance for side effects is a factor. Both have similar gastrointestinal side effects, but Ozempic could also cause injection site reactions.
• Cost and insurance coverage: Insurance and savings programs will impact your decision. Both are expensive drugs, costing around $1,000 per month without insurance. Check with your insurance provider to see if they cover Rybelsus or Ozempic for your condition and find out the associated copays for both drugs to determine your out-of-pocket costs. You should also check your eligibility for the manufacturer’s savings card programs, which provide significant savings to eligible individuals with commercial insurance coverage.
• Individualized treatment: Choose between Rybelsus and Ozempic based on your individual needs, medical history, and treatment goals. Speak with your healthcare provider to find out which medication is right for you. They will consider blood sugar control, weight loss goals, and any health risks for your situation.

Frequently asked questions

Which medication is more effective for lowering A1c?

Ozempic is generally more effective than Rybelsus for lowering A1c levels. Ozempic typically reduces A1c by 1% to 1.5%, while Rybelsus reduces it by about 0.8% to 1%.

Which medication works better for weight loss?

Ozempic is generally more effective for weight loss compared to Rybelsus. Ozempic can help people lose around 5% to 15% of their body weight, while Rybelsus typically leads to less significant weight loss of about 5%.

Which medication has fewer side effects?

Rybelsus may have fewer side effects for some people because it’s taken as a pill rather than an injection, which can make it gentler on the stomach. However, both medications have similar side effects, like nausea and digestive issues.

Can I switch from Rybelsus to Ozempic (or vice versa)?

Yes, you can switch from Rybelsus to Ozempic (or vice versa), but it’s important to talk to your doctor first to ensure the switch is safe and appropriate for your condition. They can guide you on the best way to make the change.

What if I forget to take my Rybelsus dose?

If you forget to take your Rybelsus dose, take it as soon as you remember, but only if it’s within 12 hours of your usual time. If it’s been more than 12 hours, skip the missed dose and take your next dose at the usual scheduled time.

How do I store Rybelsus and Ozempic?

Store Rybelsus at room temperature (68°F to 77°F or 20°C to 25°C), away from moisture and light. Keep it in its original packaging to protect it from moisture and light. Store unused Ozempic pens in the refrigerator (36°F to 46°F or 2°C to 8°C). Once in use, you can keep Ozempic at room temperature for up to 56 days. Do not freeze Ozempic.

Can Rybelsus replace Ozempic?

Rybelsus and Ozempic work similarly, but they are not interchangeable. Rybelsus is an oral medication, while Ozempic is an injectable, so whether one can replace the other depends on your doctor’s recommendation based on your needs.

Bottom line

Rybelsus and Ozempic are both effective medications for weight loss (off-label) and managing type 2 diabetes, but they differ in how they are taken and their potential benefits.

Rybelsus is an oral semaglutide tablet taken daily, and Ozempic is a weekly injection. Both diabetes medications contain the same active ingredient, semaglutide, and work by improving blood sugar control and aiding in weight loss.

Ozempic may be more effective for weight loss and reducing A1c levels, while Rybelsus offers the convenience of being a pill.

Which medication is right for you depends on your personal preferences, treatment goals, and medical history.

If you’re unsure whether Rybelsus or Ozempic is right for you, talk to your healthcare provider. They can help you compare the benefits and risks of each medication to decide on the best option.