Rybelsus vs. Ozempic: What's the Difference? (2024)

When comparing Rybelsus vs. Ozempic, you may be aware of their similarities. As two type 2 diabetes medications in the same prescription drug class (glucagon-like peptide-1 (GLP-1) agonists), both non-insulin options help to lower blood sugar and expedite weight loss.

However, when deciding which medication might be right for you, it's helpful to consider some distinct differences between the two, such as dosage form, route of administration, and dosing frequency.

A healthcare provider can help you determine whether Rybelsus (semaglutide) or Ozempic (semaglutide) is the right choice for you.

Rybelsus vs. Ozempic: What's the Difference? (1)

Rybelsus vs. Ozempic: What’s the Difference?

Rybelsus and Ozempic share many similarities but have a few important differences.

The main differences center around the dosage forms, frequency, strengths, and dosing schedules of the two medications.

Dosage Differences

Form and Administration:

  • Rybelsus is available as an oral tablet. Take Rybelsus with no more than 4 ounces (oz.) of water about 30 minutes before your first food, beverage, or other oral medication for best results. Don't crush, cut, or chew Rybelsus tablets.
  • Ozempic is available in a prefilled injection pen, administered subcutaneously (directly under the skin). You can inject Ozempic at any time of day, with or without food.

Frequency:

  • Rybelsus is taken orally once daily.
  • Ozempic is given as an injection once weekly.

Strengths and Dosing Schedules:

Rybelsus tablets are available in 3 milligrams (mg), 7 mg, and 14 mg strengths. The typical starting dosage is 3 mg once daily and increases slowly, over several months, until you reach the target dose of 7-14 mg once daily. This is the dosage shown to control blood glucose (sugar) levels.

Ozempic injection pens have several strengths: 2 mg per 3 milliliters (mL), 2 mg/1.5 mL, 4 mg/3 mL, and 8 mg/3 mL. Each pen contains 0.25 mg, 0.5 mg, 1 mg, or 2 mg. The typical starting dosage of Ozempic is 0.25 mg once weekly. Your dose increases slowly, over several months, until you reach the target dose of 0.5 mg, 1 mg, or 2 mg once weekly.

The table below summarizes some key differences between Rybelsus and Ozempic:

Rybelsus vs. Ozempic: Dosing Guidelines
RybelsusOzempic
Dosage FormOral tabletSubcutaneous injection
FrequencyOnce dailyOnce weekly
Typical Starting Dosage3 mg once daily for 30 days, then increase to 7 mg once daily. If your blood glucose levels are still too high after another 30 days, your provider may increase your dose to 14 mg once daily.0.25 mg once weekly for the first 4 weeks, then increase to 0.5 mg once weekly. If your blood glucose levels are still too high, your provider may continue to increase your dose every 4 weeks until you reach the amount that’s effective for you.
Typical Maintenance Dosage7 mg or 14 mg once daily0.5 mg, 1 mg, or 2 mg once weekly
Maximum Dose14 mg once daily2 mg once weekly

Uses and Ingredients

Rybelsus and Ozempic are brand-name medications with the same active ingredient: semaglutide. Semaglutide, a GLP-1 agonist, works by mimicking a natural protein to stimulate insulin secretion.

The Food and Drug Administration (FDA) has approved both Rybelsus and Ozempic for controlling blood sugar levels in adults with type 2 diabetes, along with diet and exercise.

Ozempic is also FDA-approved to lower the risk of serious cardiovascular problems—mainly heart attack or stroke—in adults with type 2 diabetes.

Healthcare providers also prescribe GLP-1 agonists for weight loss. During clinical trials, people with and without type 2 diabetes who took Rybelsus or Ozempic experienced significant weight loss.

Based on these results, providers sometimes prescribe Rybelsus or Ozempic off-label to assist in weight management for overweight or obese individuals.

However, this would be an off-label use since Rybelsus and Ozempic are not specifically FDA-approved for weight loss.

Which Is More Effective?

So far, no studies directly compare the effectiveness of Rybelsus and Ozempic. However, the results of two separate but similar clinical trials allow for a robust comparison of the effectiveness of each.

Overall, Rybelsus and Ozempic provide similar blood glucose levels and weight reduction. In clinical trials, Ozempic (1 mg weekly) and Rybelsus (14 mg daily) resulted in decreases in hemoglobin A1c (a measurement reflecting your average blood glucose levels over the past three months) of 1.6% and 1.4%, respectively.

In addition, Ozempic (1 mg weekly) and Rybelsus (14 mg daily) led to a weight loss of 9.9 pounds and 8.2 pounds over about 30 weeks, respectively. These results suggest that Rybelsus (14 mg daily) and Ozempic (1 mg weekly) are similarly effective.

Note that 14 mg daily is the maximum dose of Rybelsus, equivalent to 1 mg weekly of Ozempic.

However, a healthcare provider may prescribe up to 2 mg weekly for Ozempic.

In studies, people taking Ozempic (2 mg weekly) experienced even more weight loss and A1c reduction than those taking Ozempic (1 mg weekly).

Side Effects and Safety

Since Rybelsus and Ozempic contain the same active ingredient (semaglutide), they have similar side effects.

Most side effects for Rybelsus and Ozempic are mild and occur more frequently when you first start treatment or after the dose increases.

However, continuously monitor for emergency side effects if taking Rybelsus or Ozempic.

If any side effects begin to worsen or affect your ability to take either drug, contact your healthcare provider immediately.

Common Side Effects

Some of the more common side effects of Rybelsus and Ozempic include:

  • Nausea
  • Abdominal pain
  • Diarrhea
  • Vomiting
  • Constipation

Specific side effects of Rybelsus or Ozempic are unique to each drug. During separate clinical trials, Rybelsus caused decreased appetite in 6% to 9% of participants.

With Ozempic, fewer than 1% of participants experienced reduced appetite. In addition, Ozempic may cause injection site reactions or discomfort.

Severe Side Effects

Rarely, treatment with Rybelsus or Ozempic may result in more severe side effects. Certain medical conditions or other medications can increase the risk of severe side effects.

Some of the more severe side effects of Rybelsus and Ozempic may include:

  • Acute kidney injury: A short-term reduction in kidney function may occur, especially in people with preexisting kidney problems. Symptoms can include reduced urination, fatigue, or confusion.
  • Hypoglycemia: If you take Rybelsus or Ozempic with other diabetes medications, such as insulin, you may be at risk for hypoglycemia (low blood sugar). Symptoms of low blood sugar may include dizziness, sweating, headache, and blurred vision. Without prompt treatment, hypoglycemia can become severe or even life-threatening. Monitor your blood glucose levels according to your provider’s instructions.
  • Complications with diabetic retinopathy: Diabetic retinopathy is an eye condition resulting in damage to the blood vessels in the eye that can occur in people with diabetes. Over time, this may lead to vision loss or blindness. When blood glucose control improves with Rybelsus or Ozempic, a temporary worsening of diabetic retinopathy may occur.
  • Gallbladder disease: During clinical trials, inflammation of the gallbladder or gallstones was reported during Rybelsus and Ozempic therapy. These conditions may cause symptoms of abdominal pain, fever, or yellowing of the skin and eyes (also known as jaundice).
  • Pancreatitis: Inflammation of the pancreas may occur. Possible symptoms include severe abdominal pain and vomiting.
  • Allergic reaction: You should not take Rybelsus or Ozempic if you are allergic to either drug, its ingredients, or another GLP-1 agonist drug.
  • Ileus: Symptoms include abdominal pain, vomiting, nausea, constipation, bad breath, and abdominal fullness.

Boxed Warning

Rybelsus and Ozempic have a boxed warning for the risk of thyroid C-cell tumors. The FDA requires boxed warnings for drugs that may cause potentially severe or dangerous side effects.

Rybelsus and Ozempic caused thyroid tumors in mice and rats during animal studies. It isn’t known if the same effect could occur in humans.

As a precaution, however, Rybelsus and Ozempic are not recommended for people with a personal or family history of medullary thyroid carcinoma (MTC), a type of thyroid cancer, as well as those with multiple endocrine neoplasia syndrome type 2 (MEN 2).

Rybelsus vs. Ozempic: Which One Should I Take?

The choice between Rybelsus and Ozempic depends on the patient’s goals, preferences, and the professional opinion of their healthcare provider.

If you want to avoid needles, you might prefer Rybelsus tablets. Sometimes, insurance plans might cover one or the other, so cost is another consideration.

Switching between Rybelsus and Ozempic is possible. You might switch due to a change in your insurance coverage or personal preference, such as injection site irritation from Ozempic.

Talk to a healthcare provider before stopping or switching any medications.

Wegovy: Similar to Rybelsus and Ozempic

Wegovy is another brand-name prescription drug. It also contains semaglutide, the active ingredient in both Rybelsus and Ozempic.

Wegovy, however, is approved by the FDA specifically for weight management in adults and children ages 12 and older who have obesity or medical conditions related to being overweight.

Summary

Rybelsus and Ozempic have many similarities but also have significant differences. They both contain the same active ingredient, semaglutide.

Rybelsus is an oral tablet version of semaglutide taken once daily, while Ozempic is a subcutaneous injection administered once weekly.

Both medications lower blood glucose levels and aid in weight loss. Both drugs are used to treat type 2 diabetes, while Ozempic is also used to reduce the risk of heart attack and stroke in people with type 2 diabetes and heart disease.

A healthcare provider can help determine which option may be right for you.

10 Sources

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

  1. Han SH, Safeek R, Ockerman K, et al. Public interest in the off-label use of glucagon-like peptide 1 agonists (Ozempic) for cosmetic weight loss: a Google Trends analysis.Aesthet Surg J. 2023;sjad211. doi:10.1093/asj/sjad211

  2. MedlinePlus. Semaglutide.

  3. DailyMed. Label: Rybelsus- oral semaglutide tablet.

  4. DailyMed. Label: Ozempic- semaglutide injection, solution.

  5. MedlinePlus. Semaglutide injection.

  6. Ghusn W, De la Rosa A, Sacoto D, Cifuentes L, Campos A, Feris F, Hurtado MD, Acosta A. Weight loss outcomes associated with semaglutide treatment for patients with overweight or obesity. JAMA Netw Open. 2022;5(9):e2231982. doi:10.1001/jamanetworkopen.2022.31982

  7. Food and Drug Administration. Medications containing semaglutide marketed for type 2 diabetes or weight loss.

  8. Meier, JJ. Efficacy of semaglutide in a subcutaneous and an oral formulation. Front Endocrinol. 2021;12:645617. doi:10.3389/fendo.2021.645617

  9. Frias, JP, Auerbach, P, Bajaj, HS, et al. Efficacy and safety of once-weekly semaglutide 2.0mg versus 1.0mg in patients with type 2 diabetes: a double-blind, randomised, phase 3b trial. Lancet Diabetes Endocrinol. 2021;9(9):563-574. doi:10.1016/S2213-8587(21)00174-1

  10. DailyMed. Label: Wegovy- semaglutide injection, solution.

Rybelsus vs. Ozempic: What's the Difference? (2)

By Patricia Weiser, PharmD
Patricia Weiser, PharmD, is a licensed pharmacist and freelance medical writer. She has more than 14 years of professional experience.

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