Rybelsus vs Ozempic for weight loss: Which to choose?
Key Points
- Rybelsus and Ozempic both contain the active ingredient semaglutide.
- Rybelsus comes as an oral tablet, while Ozempic is available as an injection.
- Both Rybelsus and Ozempic are FDA approved to treat adults with Type 2 diabetes.
- In separate clinical trials, patients lost up to 3.7 kg (8 lbs) over 26 weeks of taking Rybelsus, and up to 4.7 kg (10 lbs) over 30 weeks with Ozempic.
What are Rybelsus and Ozempic?
Rybelsus and Ozempic are two FDA-approved medications that may be used to treat Type 2 diabetes (T2D) in adults. Ozempic may also be used to lower the risk of major heart events in people with Type 2 diabetes and heart disease, and reduce the risk of worsening kidney disease in adults with T2D and chronic kidney disease. Both medications contain semaglutide as the active ingredient, and belong to the drug class called glucagon-like peptide 1 (GLP-1) receptor agonists.
Rybelsus is available as an oral tablet that is taken at least 30 minutes before the first food or drink of the day. It is taken by mouth once a day. The tablets must be swallowed whole, and cannot be split, crushed, or chewed.
Ozempic comes as an injection that is administered under the skin once a week. It can be given with or without food. It’s occasionally prescribed off-label for weight loss, but there is another version called Wegovy that is FDA approved for managing weight in certain people.
Is Ozempic or Rybelsus Better For Weight Loss?
There are not any head-to-head clinical trials comparing weight loss from Rybelsus and Ozempic. An observational study of patients taking Rybelsus or Ozempic found that both groups experienced similar weight loss (around 6 kg, or 13 lbs) 6 months after starting treatment. Both medications led to some weight loss during separate clinical trials: Patients taking Rybelsus lost up to 3.7 kg (8 lbs) over 26 weeks, while patients taking Ozempic lost up to 4.7 kg (10 lbs) over 30 weeks.
Why the Difference?
The absorption rate may explain this effectiveness gap. Oral semaglutide has approximately 0.4% to 1% bioavailability compared to 89% for the injectable forms, meaning significantly less medication reaches your bloodstream despite taking the same active ingredient.
More recent studies have examined the effects of a higher dose of oral semaglutide on weight loss (not FDA-approved):
- In one study, adults with type 2 diabetes who were identified as overweight or obese took 50 mg of semaglutide once a day. Researchers found that after 68 weeks more patients taking semaglutide lost at least 5%of their body weight compared to those taking a placebo (no active medication). On average, patients taking semaglutide lost around 15% of their body weight compared to only around 2% in patients taking a placebo.
How Do Rybelsus and Ozempic Work for Weight Loss?
While neither medication is FDA-approved for weight loss, some people lose weight while taking them. They may help by:
- Slowing stomach emptying, leading to prolonged feelings of fullness
- Reducing appetite and calorie intake
How Do You Take Rybelsus and Ozempic?
Rybelsus and Ozempic are available in different dosage forms and are taken differently.
Rybelsus (oral tablet)
- Strengths: R1 formulation 3 mg, 7 mg, and 14 mg, and R2 formulation 1.5 mg, 4 mg, and 9 mg
- Usual dosing: Starting dose is 3 mg by mouth once a day (1.5 mg if taking R2 formulation) for 30 days. Then, the dose is increased to 7 mg (4 mg for R2 formulation) once a day. After 30 days, the dose may be increased to 14 mg (9 mg for R2 formulation) once a day if your blood sugar is not well controlled.
Ozempic (injection)
- Strengths: 0.25 mg, 0.5 mg, 1 mg, or 2 mg.
- Usual dosing: Starting dose is 0.25 mg injected under the skin once a week for 4 weeks. Then, the dose is increased to 0.5 mg once a week. After 4 weeks, the dose may be increased to 1 mg once a week if you need more blood sugar control. It may be raised again after 4 weeks to 2 mg once a week, which is the maximum recommended dose per week.
How Do the Side effects of Rybelsus and Ozempic Compare?
Both medications have similar side effects, but Ozempic may cause more injection site reactions.
Related questions
- Mounjaro vs Ozempic: Which is right for you?
- Ozempic Side Effects to Watch For
- What are the long-term side effects of Ozempic?
Rybelsus common side effects:
- Nausea (11-20%)
- Stomach pain (10-11%)
- Diarrhea (9-10%)
- Poor appetite (6-9%)
- Vomiting (6-8%)
- Constipation (5-6%)
Ozempic common side effects:
- Nausea (16-20%)
- Vomiting (5-9%)
- Diarrhea (9%)
- Stomach pain (6-7%)
- Constipation (3-5%)
More rare but serious side effects can happen with these medications, including:
- Pancreatitis
- Vision problems
- Low blood sugar
- Kidney damage
- Serious allergic reaction
- Gallbladder problems
- Bowel obstruction
The active ingredient in Rybelsus and Ozempic, semaglutide, has caused thyroid tumors in animals. It is not known if they have the same effect in humans, but there have not been reports of cancer due to taking either medication.
Neither medication is recommended during pregnancy or breastfeeding because of potential risks of harm to babies.
Storage and Handling of Rybelsus and Ozempic
Rybelsus tablets should be stored at room temperature in a dry place away from moisture until the expiration date on the bottle. Ozempic, on the other hand, should be stored in the refrigerator until used. Once an Ozempic pen has been opened, it can be kept at room temperature or in the refrigerator for up to 56 days.
Cost and Insurance Considerations
When choosing between Rybelsus and Ozempic for weight loss, the financial impact often plays a decisive role in treatment decisions. Both medications carry substantial monthly costs that can create barriers to long-term adherence, making it essential to understand your insurance coverage options and available cost-saving strategies before starting treatment. Because neither Rybelsus nor Ozempic are FDA approved for weight loss, it can be difficult to obtain insurance coverage for these medications when they are prescribed off-label for weight loss.
Average Monthly Costs (Without Insurance):
- Rybelsus: $982 per month
- Ozempic: $997 per month
Prices are based on the free Drugs.com discount card for cash-paying patients, and may vary depending on pharmacy location and other factors. Most people do not pay the manufacturer listing price, since patient assistance programs and coupons are available.
Can You Switch From Ozempic to Rybelsus?
Yes, it is possible to switch from Ozempic to Rybelsus and the other way around. The maker of Rybelsus recommends starting Rybelsus one week after stopping 0.5 mg of Ozempic. Your healthcare provider will give you specific instructions for how to switch between these two medications.
Decision-Making Framework: Which Is Right for You?
Choosing between Rybelsus and Ozempic for weight loss ultimately comes down to balancing your weight loss goals, lifestyle preferences, medical history, and practical considerations like cost and convenience. While both medications contain the same active ingredient (semaglutide), the differences in delivery method, effectiveness, and lifestyle requirements can make one clearly better suited to your specific situation.
Rybelsus may be a better choice if:
- You have needle phobia or injection anxiety
- Taking a once-daily tablet is most convenient
- You are looking to achieve modest weight loss
- Cost is a primary concern (often lower copays)
- You travel frequently and prefer no refrigeration requirements
Ozempic may be a better choice if:
- More weight loss is your goal (10-15% range)
- You are comfortable with weekly injections
- You have cardiovascular risk factors (proven CV benefits) or chronic kidney disease
- Previous oral medications haven't been effective
- You can manage refrigerated storage
This is not all the information you need to know about Rybelsus and Ozempic for safe and effective use and does not take the place of your doctor’s directions. Review the full product information and discuss this information and any questions you have with your doctor or other health care provider.
References
- Klobucar, S., et. al. 2024. Effectiveness of Oral versus Injectable Semaglutide in Adults with Type 2 Diabetes: Results from a Retrospective Observational Study in Croatia. In: Diabetology. DOI: https://doi.org/10.3390/diabetology5010005
- Knop, F. K., et. al. 2023. Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. In: The Lancet. DOI: https://doi.org/10.1016/s0140-6736(23)01185-6
- Kommu S, Whitfield P. Semaglutide. [Updated 2024 Feb 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Accessed on July 21, 2025 at https://www.ncbi.nlm.nih.gov/books/NBK603723/
- Ozempic (semaglutide). Updated September 2023. Novo Nordisk. Accessed September 19, 2024 at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=adec4fd2-6858-4c99-91d4-531f5f2a2d79
- Rybelsus (semaglutide). Updated January 2024. Novo Nordisk. Accessed September 19, 2024 at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=27f15fac-7d98-4114-a2ec-92494a91da98
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