Among the many GLP-1 agonist medications on the market, Rybelsus is notable for being the only oral option, making it attractive for people who want to steer clear of injections. But while the way you take the medication is different from other GLP-1s, the potential side effects are very similar — not surprising since the active ingredients are doing the same thing in your body. If you’re considering starting this medication, here’s what you should know about Rybelsus’s side effects.
What is Rybelsus?
Rybelsus is a prescription glucagon-like peptide-1 (GLP-1) receptor agonist medication, approved in 2019 by the Food & Drug Administration to treat type 2 diabetes in adults when combined with diet and exercise. It mimics the action of GLP-1, a hormone that’s produced naturally in the body. As a result, it suppresses appetite, slows down gastric emptying, and increases insulin secretion to help control blood sugar.
Like the injectable GLP-1s Ozempic and Wegovy, its active ingredient is semaglutide. But while Ozempic and Wegovy are administered with a weekly injection, Rybelsus is an oral tablet you take once per day — in the morning on an empty stomach with no more than four ounces of water. Typically, people will start on the lowest dose (3 mg) and stay on that for about a month to give the body time to adjust. Then, their dosage is increased to 7 mg, explains Dr. Rachel Pessah-Pollack, M.D., an endocrinologist and clinical professor of endocrinology, diabetes and metabolism at NYU Langone Health Department of Medicine. If they’re tolerating that, they may be bumped up to the highest dosage (14 mg) after another month.
Common side effects of Rybelsus
Not everyone will have side effects while on a Rybelsus prescription, but if you do, they will likely be gastrointestinal. The drug causes food to stay in the stomach longer and prolongs digestion, which may cause nausea or other GI upset, says Dr. Christopher McGowan, M.D., a board-certified gastroenterologist and obesity medicine physician in Cary, North Carolina.
Here are the most common side effects you may experience when taking Rybelsus:
- Nausea: Occurs in about 11% (7 mg dose) to 20% (14 mg dose) of patients, compared to 6% on a placebo.
- Diarrhea: Occurs in about 9% (7 mg) to 10% (14 mg) of patients, compared to 4% on a placebo.
- Vomiting: Occurs in about 6% (7 mg) to 8% (14 mg) of patients, compared to 3% on a placebo.
- Stomach (abdominal) pain: Occurs in about 10% (7 mg) to 11% (14 mg) of patients, compared to 4% on a placebo.
- Decreased appetite: Occurs in about 6% (7 mg) to 9% (14 mg) of patients, compared to 1% on a placebo.
- Constipation: Occurs in about 6% (7 mg) to 5% (14 mg) of patients, compared to 2% on a placebo.
For a full list of Rybelsus side effects, review the medication guide.
Mild side effects of Rybelsus
The majority of Rybelsus’s side effects are mild and are most prevalent at the highest (14 mg) dosage of Rybelsus and when people first start on the medication. “They should improve over time,” says McGowan.
Here are the mild side effects of Rybelsus:
- Abdominal pain
- Bloating and gas
- Constipation
- Diarrhea
- Gastroesophageal reflux disease (GERD)
- Heartburn
- Indigestion
- Mild allergic reaction
- Nausea and vomiting
Serious and long-term side effects of Rybelsus
Although they’re rare — occurring in 1% of people or less — some possible side effects of Rybelsus are more severe. These include:
- Gallbladder problems: ”GLP-1 medications do have an increased risk for gallstones and gallbladder disease, especially when weight loss is rapid,” McGowan says. Keep an eye out for signs a gallstone is blocking bile ducts in the gallbladder, which includes pain in the upper right abdomen, often in the evening following a heavy meal. If the pain lasts for several hours, is very intense, or is accompanied by vomiting or a fever, you should seek medical care.
- Hypoglycemia (low blood sugar levels): It’s rare for blood sugar levels to drop too low while on Rybelsus, McGowan says, but it can happen. This is especially true if you are taking Rybelsus alongside other diabetes medications like insulin. Signs of hypoglycemia include sweating, shakiness, and dizziness. Eat something with carbs right away, like fruit juice or candy, to get your blood sugar back up.
- Kidney problems: GLP-1 medications don’t affect the kidneys directly, McGowan says, but dehydration from vomiting, diarrhea, or simply not drinking enough water can cause kidney problems. This is of particular concern in the beginning of treatment, as side effects like nausea (which can cause vomiting) tend to be most pronounced then. To minimize this risk, people with existing renal conditions or people who have more severe GI problems on Rybelsus should be carefully monitored.
- Pancreatitis: Pancreatitis, or inflammation of the pancreas, is uncommon while taking Rybelsus, but it can happen. Research suggests pancreatitis occurs because of the medication’s action on the pancreas and insulin production. It’s characterized by sharp abdominal pain that can radiate to the back, along with vomiting in some cases. Pancreatitis needs immediate medical attention, so reach out to your doctor right away.
- Risk of thyroid cancer: Rybelsus comes with an FDA warning that taking the medication can increase the risk of one type of thyroid tumor: C-cell tumors. But these tumors have been observed only in rodents and are typically not the same type of tumors humans get when they develop thyroid cancer. Research has found there is no link between GLP-1 use and the development of new thyroid (or pancreatic) cancers in people. That said, it’s still included as a risk, and people with a history of certain thyroid cancers are advised not to use Rybelsus or other GLP-1s.
Explanation of Rybelsus side effects
Nausea gets the most attention when it comes to the side effects for Rybelsus and other GLP-1 medications, but here’s a deeper dive into some of the others.
Thyroid cancer risk
While this is included as a possible side effect, it’s not confirmed to happen in people. “The data has shown there’s a potential risk of medullary thyroid cancer in animal models, and as a result, we use caution if there's a personal or family history of those specific types of issues,” Pessah-Pollock says. In fact, Rybelsus and other GLP-1s are not recommended for people who have a personal or family history of medullary thyroid cancer, which is a rare form of thyroid cancer.
Tips for managing or identifying thyroid cancer
If you have the following symptoms, it does not necessarily mean you have cancer, but you should let your provider know.
- A lump in the front or side of the neck, sometimes growing quickly
- Swelling or pain in the neck
- Hoarseness or other voice changes that do not go away
- Trouble swallowing or breathing
- A persistent cough that’s not due to a cold
Weight loss
Rybelsus is not FDA-approved for weight loss, but it reduces your appetite, so people prescribed the medication often lose some weight. Usually, though, people don’t lose as much weight while taking Rybelsus as they do on one of the injectable GLP-1 medications that’s been FDA-approved for weight loss, like Wegovy or Zepbound, says Pessah-Pollock. For instance, one study found that people lost an average of 8.4 pounds after taking 14 mg of Rybelsus for six months. In comparison, Wegovy — the injectable semaglutide GLP-1 approved for weight loss — resulted in an average weight loss of 15% in 68 weeks, which came to about 35 pounds.
Tips for managing weight loss
A decreased appetite is a common side effect of Rybelsus and other GLP-1 medications, so it’s important to make sure you’re getting all the important nutrients you need from the foods you do eat. Shedding too many pounds too quickly can lead to nutrient deficiencies, muscle loss, and fatigue. Prioritize lean protein and foods with plenty of fiber, such as vegetables, whole grains, and fruit.
Constipation
Slowed-down digestion can lead to constipation in people taking GLP-1 medications, including Rybelsus. Constipation is defined as having fewer than three bowel movements in a week or having stools that are hard, dry, and painful or difficult to pass.
Tips for managing constipation
Drinking lots of water and eating small, nutrient-dense meals can keep things moving. Eating plenty of lean proteins, fiber-rich vegetables, and whole grains can also help prevent and ease constipation, McGowan says.
Warnings for Rybelsus
There are a few things everyone should be aware of before taking Rybelsus.
Boxed warning: Risk of thyroid cancer
Rybelsus has a “black box” warning — the FDA’s most serious warning — about the risk of thyroid cancer. It’s important to note the warning is based on clinical trials on rodents, and no evidence has been found in humans.
Other warnings
Rybelsus is also not recommended for people who have a personal or family history of multiple endocrine neoplasia, which is a group of disorders that can cause tumors to grow on endocrine glands. And if you have a history of pancreatitis, your doctor will also probably not prescribe it, McGowan says.
The bottom line
Rybelsus is the only FDA-approved oral GLP-1 medication to treat type 2 diabetes. The side effects are the same as with injectable GLP-1 medications, like Ozempic or Wegovy. The most common side effects of Rybelsus are nausea, abdominal pain, vomiting, constipation, and decreased appetite. Not everyone will experience these side effects, and they usually go away on their own after a few weeks on the medication. There are some other more serious side effects, including pancreatitis, but these are very rare.
FAQs
“No, not generally,” McGowan says. “Rybelsus has a very favorable safety profile. Serious side effects are rare, and most patients tolerate it well after the initial adjustment period.”
Rybelsus and Ozempic have the same active ingredient: semaglutide. As a result, one doesn’t tend to be safer than the other. That said, Rybelsus is absorbed through the stomach lining instead of entering the bloodstream directly. “Because Rybelsus is absorbed through the GI tract, some patients may experience more nausea or stomach upset, especially if they don't take it exactly as recommended, but both are generally safe and well tolerated when used appropriately,” McGowan says.
There is not a strict list of foods you can’t eat on Rybelsus, but Pessah-Pollock recommends avoiding fried foods and high-fat foods, as they can make nausea and other GI side effects worse. As for beverages, alcohol may irritate the stomach and carbonated beverages may increase bloating and reflux.
This content is for informational purposes only and does not constitute medical advice, diagnosis or treatment. It should not be regarded as a substitute for guidance from your healthcare provider.