Rybelsus (semaglutide): Overview, how it works, and more

If you have type 2 diabetes, you have a range of medication options for helping manage your blood sugar, and one of those choices is Rybelsus. Like Ozempic and Mounjaro, it’s a glucagon-like peptide-1 receptor agonist (aka GLP-1), but it differs in a big way. Rybelsus is a daily pill as opposed to a weekly injection. That may sound more appealing — especially if you’re nervous about shots — but there are some key things to know when considering if aRybelsus prescriptionis right for your health needs.

Rybelsus is a brand name for the medication semaglutide that was approved by the Food and Drug Administration (FDA) for type 2 diabetes management in September 2019. Taken as a daily pill, it’s in the class of medications known as GLP-1s (also in that category: Ozempic, Wegovy, Mounjaro, andZepbound). These medications mimic the GLP-1 hormone to improve insulin response, control appetite, and help you feel full longer — all things that can lead to better blood sugar control.

Currently, there is no generic version of oral semaglutide (the active ingredient in Rybelsus) because the brand is still protected under its patent. It isn’t expected to expire until 2033, which is when you might find generic versions available.

Similar to other GLP-1s like Ozempic, Rybelsus is approved to help those with type 2 diabetes manage their blood sugar.

When combined with regular physical activity and healthy eating, Rybelsus can help lower A1C levels in people with type 2 diabetes. Research shows that Rybelsus lowers A1C levels by an average of 1% to 1.3%, depending on the dose. And although it’s not approved specifically for weight loss, you may lose some. In one study, for example, participants lost around 8.4 pounds after taking 14mg of Rybelsus for six months.

"Although this has the same active ingredient, semaglutide, as Ozempic, it wouldn't [typically] be used off-label for weight loss," says Dr. Sue Decotiis, M.D., a triple board-certified physician in internal medicine, antiaging medicine, and obesity medicine, who leads a weight-loss practice in Scarsdale, NY. "There are otherweight-loss medicationsthat work better." For example, the injectable version of semaglutide approved for weight loss,Wegovy, leads to an average weight loss of 15% in 68 weeks.

Taken as an oral medication, Rybelsus mimics a natural hormone in the body, glucagon-like peptide 1, that keeps blood sugar levels controlled. Your body produces GLP-1 whenever you eat, signaling to the pancreas to release insulin as a way to control blood sugar. Rybelsus has the same impact as the naturally occurring hormone, but for an extended period of time.

GLP-1 medications like Rybelsus also slow the rate of stomach emptying, which not only helps you feel full for longer — contributing to modest weight loss — but is another factor for improving insulin response, according to Dr. Paunel Vukasinov, M.D., a double board-certified physician in internal medicine and obesity medicine, who practices at Medical Offices of Manhattan in New York.

Most GLP-1s are delivered through an injection pen, but because Rybelsus is a tablet, it may be appealing to those who'd rather not go the injection route, Vukasinov says. "There are several type 2 diabetes medications that involve injecting yourself, such as Ozempic, but some people have difficulty doing that at home, or they have a fear of needles,” says Vukasinov. “In those cases, Rybelsus would be a good choice."

Rybelsus comes in three dosages: 3 mg, 7 mg, and 14 mg. No matter which dose you’re taking, you should have the pill in the morning with a small bit of water 30 minutes before your first meal or beverage. It’s important to follow these directions. If you take the medicine with food in your stomach, it may lessen the effect of Rybelsus. And if you wait more than 30 minutes to eat something, it might speed up the absorption rate and lead to more side effects.

Most people start taking Rybelsus with the 3 mg dose once daily for 30 days. After that, the dosage may be increased to 7 mg daily if your blood sugar is not being adequately controlled. After 30 days at that dosage, your doctor will check your blood sugar levels and decide if you should stay there or move up to 14 mg daily.

"Rybelsus can have side effects similar to other medications that have semaglutide as an active ingredient," Vukasinov says, adding that the intensity, duration, and frequency of side effects can range from person to person. Here’s what to look out for.

The most common side effects for Rybelsus are:

• Nausea

• Constipation

• Decreased appetite

• Diarrhea

• Stomach pain

• Vomiting

These don’t happen to everyone, with about 20% of people having nausea and 11% having abdominal pain, for example. Similar to other GLP-1 medications, you’re most likely to experience side effects when first starting the drug or when you’re increasing the dosage. For the full list of side effects, visitthe Rybelsus site.

The most serious side effect mentioned for Rybelsus is the risk of thyroid tumors. However, this warning is based on animal studies. Researchers haven’t found a connection to people taking Rybelsus and these tumors. That said, the manufacturer of Rybelsus urges anyone to let their healthcare provider know if they get a lump or swelling in your neck, or have hoarseness, trouble swallowing, or shortness of breath while taking Rybelsus.

If you are comfortable giving yourself an injection, you can talk with your provider about other GLP-1s like Ozempic (the injectable form of semaglutide),Mounjaro (tirzepatide), Victoza (liraglutide), andTrulicity (dulaglutide). In addition to GLP-1s, other medications that can lower blood sugar include:

• Metformin

• DPP-4 inhibitors like linagliptin (Tradjenta) and sitagliptin (Januvia)

• SGLT2 inhibitors like empagliflozin (Jardiance) and dapagliflozin (Farxiga)

• Sulfonylureas like glimepiride (Amaryl) and glyburide (Diabeta)

• TZDs like rosiglitazone (Avandia) and pioglitazone (Actos)

According to the FDA, you should be aware that some people in Rybelsus trials developed the following health issues:

• Pancreatitis

• Diabetic retinopathy complications

• Hypoglycemia

• Hypersensitivity reactions

• Acute kidney injury

• Acute gallbladder disease

These outcomes were rare and didn’t occur in significant enough numbers for the FDA to issue a caution about the medication.

There is also insufficient data about use of semaglutide in pregnant women and there is some evidence in animal studies that a fetus could be affected by the drug during pregnancy. Because of that, both Rybelsus and other GLP-1 medications like Ozempic are not recommended for use during pregnancy.

Before starting any medication, it’s important to discuss what you’re already taking with your provider — some over-the-counter or prescription drugs may interact with Rybelsus. These include:

• Blood sugar-lowering medications

• Diuretics

• Thyroid medications

• Blood pressure medications

Also, be cautious when drinking alcohol when taking Rybelsus, since that may affect blood glucose levels in the form of either hypoglycemia (low blood sugar) and hyperglycemia (high blood sugar), depending on how much and how often you drink. Particularly avoid drinking alcohol on an empty stomach or following exercise when taking Rybelsus, which can increase risk of hypoglycemia.

Rybelsus retails for $1,029 for a 30-day supply of 30 tablets, and how much of that is covered by insurance will depend on your plan. However, many companies cover medications like Rybelsus for type 2 diabetes management. If you have to pay for some or all of the cost, you may be able to use asavings card from the manufacturer. Those who are eligible might pay as little as $210 for a one-, two- or three-month prescription.

To be eligible, you must have a prescription for Rybelsus fortype 2 diabetesmanagement and be enrolled in a commercial drug insurance plan. You also cannot be part of any state, federal, or government-funded healthcare program such as Medicare or Medicaid.

Rybelsus is a type 2 diabetes medication taken as a daily pill. This is different from other GLP-1s, which are given via a weekly injection. Because of this, it does not result in the same weight loss as injectable GLP-1s. People who take Rybelsus start out on the lowest dose and gradually work their way up to one that controls their blood sugar adequately. Side effects tend to be mild, like nausea. As with any medication, it's essential to talk with your health provider about your goals for diabetes control to see if Rybelsus might be a fit for your needs.