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Wegovy and Rybelsus are two commonly prescribed medications for weight loss. Both medications belong to the same class of drugs called glucagon-like peptide-1 (GLP-1) receptor agonists.
While Wegovy and Rybelsus contain the same active ingredient, semaglutide, Wegovy is a once-weekly injection while Rybelsus is a once-daily tablet. Learn more about the key differences and whether one of these medications can help you achieve your health goals.
Rybelsus vs. Wegovy in Weight Loss Treatment
Wegovy is a medication first approved by the FDA in 2017 to treat type 2 diabetes. In 2021, the FDA approved Wegovy for weight loss in adults living with obesity or adults who are overweight along with a weight related-condition.
Patients who meet either of the following criteria fall under the FDA-approval to take Wegovy for weight management:
- BMI of 30 kg/m2 or greater (obesity)
- 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia)
Rybelsus is a medication approved by the FDA in 2019 for the treatment of type 2 diabetes. While not formally FDA-approved for weight loss, it is often used “off-label” to help patients lose weight.
Rybelsus vs. Wegovy: How They Work
The primary active ingredient in both Wegovy and Rybelsus is semaglutide, a GLP-1 agonist. Think of an “agonist” as a mimicker—it acts like the body’s natural GLP-1 hormone, activating receptors that regulate blood sugar and slow digestion. This allows the person taking the medication to feel fuller for longer, so they experience fewer cravings and achieve their desired weight loss goals.
When taken, semaglutide activates GLP-1 receptors in various organs, including the pancreas, stomach, and brain to promote several chain reactions that can help with weight loss and managing type 2 diabetes.
After a meal, food is broken down into glucose, our body’s main energy source. Glucose enters the bloodstream and signals the pancreas to release insulin, which then helps move glucose from the bloodstream into the body’s cells for energy. If blood sugar and insulin are constantly high, for instance, in the case of constant overeating, the body can get overwhelmed. It may not be able to make enough insulin or it may start becoming resistant to insulin. Instead of traveling to the cells to be used for energy, blood sugars begin to rise which can lead to diabetes and weight gain.
One of semaglutide’s main functions is stimulating insulin release from the pancreas. This is particularly beneficial for people with diabetes or prediabetes who have insufficient insulin production or insulin resistance.
Additionally, semaglutide slows down the rate at which food is digested and absorbed in the stomach, which can help to reduce feelings of hunger and increase feelings of fullness. This can lead to a decrease in calorie intake and subsequent weight loss.
Effectiveness of Wegovy vs. Rybelsus
Wegovy has a more robust body of evidence supporting its effectiveness in obesity treatment. However, clinical studies have found both Wegovy and Rybelsus effective for weight loss in diabetic and nondiabetic patients.
STEP 1 Trial: Wegovy was given as a once-weekly pen injection over a period of 68 weeks in addition to lifestyle modifications. Lifestyle modifications included adhering to a reduced-calorie diet (about a 500-calorie deficit) and 150 minutes of moderate physical activity per week (think: walking for 20 minutes daily). This trial found that participants taking Wegovy experienced a significant reduction in body weight compared to the placebo group. On average, patients on Wegovy who adhered to a healthy diet and exercise regimen noticed approximately a 15% reduction in body weight from their baseline compared to the placebo group (1).
PIONEER-1 trial: Though there are no current trials examining Rybelsus in managing obesity, there are studies such as the PIONEER-1 trial that show weight loss to be an added benefit of Rybelsus in adults taking the medication for type 2 diabetes. Over a period of 26 weeks, patients on average had a roughly 5 lb decrease in body weight compared to their baseline. This was seen without the participants undergoing a specific diet and exercise plan. This may mean that Rybelsus combined with diet and exercise modification may work better for weight loss than is currently known (2).
Finally, a review published in 2022 compared semaglutide in pill for, as in Rybelsus, with injectable forms and other GLP-1 agonists in diabetic patients. Overall, Rybelsus was similar to the injectable form for its weight loss effects (3).
Wegovy vs. Rybelsus Dosage and Administration
The most significant difference between Wegovy and Rybelsus is the route of administration.
Wegovy is a once-weekly injection given subcutaneously, meaning under the skin. Rybelsus is a once-daily tablet that is taken orally. They are administered in different doses since oral forms of medication need a larger dose to be properly absorbed.
For patients who are uncomfortable with needles or have difficulty administering injections themselves, Rybelsus may be a more attractive option. However, some patients may prefer the convenience of a weekly injection like Wegovy over daily pills.
Refer to the table below on the typical dosing regimen for Rybelsus vs. Wegovy. Consult your provider to determine the appropriate dosing schedule, which can depend on other medications you are taking, tolerance to the medication, starting BMI, and rate of weight loss. In both Rybelsus and Wegovy, it is typically recommended to start at a lower dose and gradually increase over time to allow your body to adjust.
Side Effects of Wygovy vs. Rybelsus
Wegovy and Rybelsus share many of the same common side effects. These side effects are usually temporary and may subside as the body adjusts to the medication. Studies show that those on Rybelsus report fewer side effects than injectable forms of semaglutide (3).
Known side effects of Wygovy and Rybelsus:
- Nausea
- Vomiting
- Diarrhea
- Constipation
- Upset stomach
- Heartburn
- Burping
- Gas and bloating
- Loss of appetite
- Fatigue
- Dizziness
Wegovy has also been linked to some serious, but rare side effects, such as pancreatitis and thyroid cancer. The risk of these side effects is low and should be weighed against the potential benefits of the medication.
Both Wegovy and Rybelsus should be avoided in patients with a history of medullary thyroid cancer or a family history of multiple endocrine neoplasia cancer syndrome type 2 (MEN-2). You should also avoid these medications if you have a history of diabetic retinopathy or if you are taking insulin, as it can increase the risk of hypoglycemia.
Wegovy vs Rybelsus: Cost and Coverage
The cost of Wegovy and Rybelsus can vary depending on factors such as insurance coverage and location. Based on the manufacturer Novo Nordisk, Wegovy has a list price of $1,349.02 per one-month supply, while Rybelsus is $935.77 per one month supply (4, 5).
It is important to check with your insurance provider to see if either medication is covered and any potential out-of-pocket costs. Novo Nordisk offers savings card options, allowing those who already have insurance coverage to pay as little as $10 a month for Rybelsus or $0 for 13 refills of Wegovy.
For those whose insurance plan will not offer coverage for weight loss medications or are not sure, there are affordable options. The team at Mochi Health can help you find out if you qualify for savings on brand-name medications or provide safe and effective alternatives such as compounded semaglutide at just $175 per month.
Key Takeaways
Rybelsus and Wegovy are effective weight-loss medications that work similarly but have some key differences. Both medications have been shown to reduce body weight in multiple studies effectively. Only Wegovy is FDA-approved for weight loss and seems more effective in achieving significant weight loss than Rybelsus. However, more side effects were reported for people taking Wegovy than those taking Rybelsus.
These medications should be taken along with diet and exercise to achieve a maximal effect. Ultimately, the best approach is to discuss with your provider to determine what medication best fits your needs.
If you want to learn more about medication-assisted weight loss, Mochi Health has board-certified obesity medicine physicians who can offer expert guidance. Find out if you’re eligible for the program today and get access to 1-on-1 provider visits, nutrition consultations, 24/7 customer support, and medications delivered to your door.
Sources:
- Wilding, J. P. H., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., McGowan, B. M., Rosenstock, J., Tran, M. T. D., Wadden, T. A., Wharton, S., Yokote, K., Zeuthen, N., & Kushner, R. F. (2021b). Once-weekly semaglutide in adults with overweight or obesity. New England Journal of Medicine, 384(11), 989–1002. https://doi.org/10.1056/nejmoa2032183
- Aroda, V. R., Rosenstock, J., Terauchi, Y., Altuntas, Y., Lalic, N. M., Morales Villegas, E. C., Jeppesen, O. K., Christiansen, E., Hertz, C. L., Haluzík, M., Belkacem, K., Chiali, N., Bourezane, S., Guermaz, R., Popivanov, P., Lefterov, I., Tankova, T., Penchev, I., Koskova, M., … Fitzgibbons, W. (2019). Pioneer 1: Randomized clinical trial of the efficacy and safety of oral semaglutide monotherapy in comparison with placebo in patients with type 2 diabetes. Diabetes Care, 42(9), 1724–1732. https://doi.org/10.2337/dc19-0749
- Alhindi, Y., & Avery, A. (2022). The efficacy and safety of oral semaglutide for glycaemic management in adults with type 2 diabetes compared to subcutaneous semaglutide, placebo, and other GLP-1 RA Comparators: A systematic review and network meta-analysis. Retrieved from https://www.sciencedirect.com/science/article/pii/S2451865422000618
- Wegovy® (semaglutide) injection 2.4 mg list price & Insurance Coverage explained: NovoCare®. NovoCare® Savings | Coverage | Support. (n.d.). https://www.novocare.com/obesity/products/wegovy/let-us-help/explaining-list-price.html
- Find out the cost for RYBELSUS®. NovoCare® Savings | Coverage | Support. (n.d.-a). https://www.novocare.com/diabetes/products/rybelsus/explaining-list-price.html
