Wegovy vs Rybelsus For Weight Loss

Wegovy (semaglutide) and Rybelsus (oral semaglutide) are two medications that have been approved by the FDA for weight loss. Both medications belong to the same class of drugs called glucagon-like peptide-1 (GLP-1) receptor agonists, and they work by mimicking the action of the hormone GLP-1, which regulates glucose metabolism and delays gastric emptying. This then allows for better appetite control, changes in food cravings, and weight loss. Despite their similarities, there are some key differences between Wegovy and Rybelsus that patients and healthcare providers should be aware of. In this blog post, we will compare and contrast the two medications to help you make an informed decision about which one may be right for you.

April 21, 2023

Mechanism of Action

As mentioned above, both of these medications are the same type of GLP-1 agonist called semaglutide. It works by mimicking the action of the hormone GLP-1, which is naturally produced in the body and regulates glucose metabolism and appetite. When semaglutide is administered, it binds to and activates GLP-1 receptors in various organs, including the pancreas, stomach, and brain. This leads to several physiological effects that can help with weight loss and the management of type 2 diabetes.

Firstly, semaglutide stimulates the release of insulin from the pancreas, which helps to lower blood glucose levels. This is particularly beneficial for people with type 2 diabetes who have insufficient insulin production or insulin resistance. In addition, 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.

Administration and Dosage

The most significant difference between Wegovy and Rybelsus is the route of administration. Wegovy is a once-weekly injection that is given subcutaneously (under the skin), while Rybelsus is a once-daily tablet that is taken orally. They are given in different doses (0.25mg for Wegovy and 3-7 mg for Rybelsus) since oral forms of medication need a larger dose in order to get past absorption in the gut and metabolism in the liver. Since Weogy is an injection, it requires a lower dose to have the same effect as Rybelsus. 

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 over daily pills.


Both medications have been shown to be effective for weight loss in both diabetic and nondiabetic patients. In the STEP 1 Trial, when Wegovy was given as a once-weekly pen injection over a period of 68 weeks, the researchers found that participants taking Wegovy experienced a significant reduction in body weight compared to the placebo group. Participants noticed a 15% reduction in body weight from their baseline when compared to the placebo group.

Though there are no current trials examining Rybelsus in managing obesity, there are studies in diabetic patients that show there appears to be an effect on weight loss. The PIONEER-1 trial was a phase 3 randomized control trial published in 2019 that participants taking Rybelsus for a period of 26 weeks showed a 2.6 kg (~5 lbs) decrease in body weight when compared to baseline. This was seen without the participants undergoing a specific diet and exercise plan. This may tell us that there may be an even more significant effect of Rybelsus in combination with diet and exercise if given for a time period similar to the STEP 1 Trial. 

A systemic review and meta-analysis published in 2022 reviewed 12 different randomized control trials to compare the weight loss effects of Rybelsus (oral semaglutide) to subcutaneous semaglutide and other GLP-1 agonists in diabetic patients. Overall, they found that Rybelsus was similar to subcutaneous semaglutide for its weight loss effects. 

Side Effects

Both Wegovy and Rybelsus can cause similar side effects, such as nausea, diarrhea, and constipation. However, because Rybelsus is taken orally, it can also cause problems with absorption and digestion. In the systemic review mentioned above, they also found that side effects were not as frequently reported as subcutaneous semaglutide. 

Some patients may experience mild-to-moderate gastrointestinal side effects when taking Rybelsus, including stomach pain, bloating, and gas. These side effects are usually temporary and may subside as the body adjusts to the medication.

Wegovy may also cause more serious side effects, such as pancreatitis and thyroid cancer. However, 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. 

Cost and Coverage

The cost of Wegovy and Rybelsus can vary depending on factors such as insurance coverage and location. As of March 2023, the average retail price of Wegovy is approximately $1,200 per month, while the average retail price of Rybelsus is approximately $950 per month. Since Wegovy has been FDA-approved for weight loss, it may be easier to find coverage. 

It is important to check with your insurance provider to see if either medication is covered, as well as any potential out-of-pocket costs. There may be discounted options for Wegovy or Rybelsus available online. 


Both Rybelsus and Wegovy are effective weight-loss medications that work in a similar way but still have some differences. Rybelsus is a once-daily tablet, while Wegovy is a once-weekly injection. Both medications have been shown to effectively reduce body weight in multiple studies, but Wegovy seems to be currently more effective in weight loss. However, more side effects were reported for people taking Wegovy when compared to Rybelsus. You should reach out to your provider to see which medications can be covered, as they both can be expensive. 

It should also be noted that these medications should be taken along with diet and exercise in order to achieve a maximal effect. Ultimately, you should have a discussion with your provider to determine what medication best fits your lifestyle. 

If you would like to learn more about GLP-1 medications or want to see if you might be eligible for medication-assisted weight loss, check out Mochi Health, where board-certified obesity medicine physicians can offer expertise in this realm!

Dr. Constantine Joseph Pella, MD

Boston University Medical Center

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