Rybelsus Side Effects (Oral Semaglutide)

Key Points

• Rybelsus commonly causes nausea, vomiting, and diarrhea, especially when starting or increasing doses
• Severe side effects are rare but include pancreatitis, kidney problems, and thyroid concerns that need immediate attention
• A balanced diet that includes lean proteins and high-fiber foods helps minimize side effects and stabilize blood sugar levels

Managing type 2 diabetes means making tough decisions about medications, and Rybelsus, the oral semaglutide pill, may be on your radar. Perhaps you prefer pills over injections like Ozempic and Wegovy, or it's what your insurance will cover.

While Rybelsus can help improve blood sugar control, understanding its side effects before starting treatment is just as important. Here's what research shows about Rybelsus side effects and how to manage them, so you can feel more prepared for what's ahead.

What is Rybelsus?

Rybelsus is oral semaglutide, a GLP-1 medication approved by the FDA to manage type 2 diabetes. Semaglutide is the same main ingredient found in well-known injectable drugs like Ozempic and Wegovy.

The FDA approved Rybelsus specifically for adults with type 2 diabetes who need better blood sugar control along with diet and exercise.

One clinical study showed a 1.2% reduction in A1C levels with a daily dose of Rybelsus over a 26-week period.

How does Rybelsus work?

Rybelsus mimics GLP-1, a natural hormone that regulates blood sugar through four key actions:

• It signals your pancreas to release insulin when blood sugar rises after meals. This helps move glucose from your bloodstream into your cells for energy. The medication only triggers insulin when needed, reducing the risk of dangerous low blood sugar.
• It tells your liver to reduce the amount of glucose released into your blood. Your liver naturally releases stored sugar throughout the day, but Rybelsus helps prevent unnecessary spikes in blood sugar levels.
• It slows gastric emptying. Food moves through your stomach more gradually, preventing sharp spikes in blood sugar after meals. This delayed digestion also creates a longer-lasting feeling of fullness, often leading to reduced food intake.
• It signals the appetite center in your brain to reduce your appetite. Overall, you’re eating less food, resulting in weight loss, which can help control type 2 diabetes.

Rybelsus administration and dosage

Rybelsus comes in three doses: 3 mg, 7 mg, and 14 mg.

The 3 mg dose is the starting dose, once daily for 30 days to help the body adjust to the medication and potentially reduce the risk of side effects.

After 30 days, your healthcare provider may increase the dose to 7mg daily. If, after another 30 days, there is a need for more blood sugar control, you may be prescribed 14mg daily, the maximum available dose. The decision to increase doses depends on your A1C levels and tolerance to the drug.

How to take Rybelsus?

Rybelsus is designed to be taken first thing in the morning on an empty stomach with no more than 4 ounces of plain water to swallow the tablet whole.

Wait at least 30 minutes before eating or drinking anything else.

This waiting period is necessary because Rybelsus (oral semaglutide) is difficult for the body to absorb. Only about 0.4% to 1% of the medication actually enters the bloodstream, even under ideal conditions.

The medication includes a special absorption enhancer to help it pass through the stomach lining, but food, beverages, or extra water can interfere with this already limited absorption process. If the medication is not taken as prescribed, even less of it will be absorbed, reducing its effectiveness.

Rybelsus takes 4-5 weeks to reach steady blood levels.

Rybelsus side effects

Common side effects

Digestive symptoms are common side effects, particularly during the first weeks or after dose increases. Nausea, vomiting, stomach pain, abdominal cramping, and diarrhea are some common side effects. Some people may also experience constipation.

“The digestive side effects of Rybelsus may improve as the body adapts to the medication. However, individual results vary, says Gia Eapen, MD. “If symptoms persist beyond a few weeks, please consult your doctor for ways to manage them.”

Serious side effects

While rare, Rybelsus can cause serious side effects that need immediate medical attention.

Rybelsus carries a warning about thyroid tumors, including cancer. Report any neck lumps, hoarseness, swallowing difficulty, or shortness of breath. People with a personal or family history of certain thyroid cancers should let their healthcare provider know before taking the drug.

Call your doctor right away if you experience severe stomach pain that won't go away and may spread to your back, as this could signal pancreatitis.

Watch for signs of low blood sugar, like shakiness, sweating, confusion, dizziness, or a fast heartbeat, especially if you take insulin or certain other diabetes medications. Contact your healthcare provider if you notice vision changes, severe or persistent stomach problems, or signs of gallbladder issues like upper stomach pain, yellowing skin or eyes, fever, or clay-colored stools

"Before starting Rybelsus, make sure to tell your doctor about any pancreas or kidney problems, diabetes-related eye issues, or upcoming surgeries," says Eapen, MD. "If you're pregnant, planning to become pregnant, or breastfeeding, it's especially important to discuss this with your healthcare provider."

What happens when you stop taking Rybelsus?

When you discontinue Rybelsus, several changes may occur. Without other diabetes treatment, your appetite may return to previous levels, often leading to weight regain.

Research shows that participants regained about two-thirds of the weight they had lost after stopping semaglutide treatment.

For those with type 2 diabetes, blood sugar levels may rise, requiring close monitoring and consultation with your doctor before stopping. Some people also experience temporary digestive adjustments as their stomach returns to its normal emptying rate.

Always work with your healthcare provider to discontinue the medication safely rather than stopping abruptly.

Importance of diet when on Rybelsus

Your food choices are important when on Rybelsus. Rybelsus works best with diet and lifestyle changes. You may see appetite reduction when on Rybelsus, which makes it all the more important to ensure that you follow a balanced diet.

"When taking Rybelsus, try the Diabetes Plate method: fill half your plate with non-starchy vegetables, one quarter with lean protein, and one quarter with complex carbohydrates," says Rita Faycurry, RD, Registered Dietitian.

Lean proteins, such as chicken, fish, tofu, and legumes, can help keep you satisfied without spiking your blood sugar. High-fiber foods, like whole vegetables and whole grains, help stabilize glucose levels. Include healthy fats from avocados, nuts, and olive oil in moderate portions for sustained energy, and stay hydrated to prevent dehydration from any digestive side effects.

Limit foods that worsen digestive side effects. For example, high-fat and fried foods may increase nausea. Spicy foods may aggravate stomach discomfort. Processed foods contain hidden sugars and unhealthy fats that can spike blood sugar levels. Be mindful of alcohol, as it can affect blood sugar levels.

A registered dietitian can help you develop a diabetes-friendly diet tailored to your specific needs, medications, and lifestyle.

Nutrition counseling with a registered dietitian is often covered by insurance for diabetes management, making this expert support accessible and affordable for most people.

Final thoughts

Rybelsus provides a convenient oral option for managing type 2 diabetes, although its effectiveness depends on proper use, a balanced diet, and regular exercise.

While digestive side effects are common initially, they often improve as the body adjusts. Clinical studies show semaglutide works best when combined with dietary changes and exercise rather than as a standalone treatment.

Get a diabetes diet plan tailored to your needs, covered by insurance.

Frequently asked questions (FAQs)

What are the disadvantages of Rybelsus?

The main disadvantages of Rybelsus may be that you have to remember to take it daily and, like other GLP-1 medications, may experience digestive side effects. Additionally, Rybelsus has lower absorption rates compared to injectable semaglutide forms, with 0.4%-1% absorbed versus nearly 89% with injections, which may reduce effectiveness for some individuals. The medication can be expensive without insurance.

What's the most common side effect of Rybelsus?

Nausea, vomiting, and diarrhea are the most frequent side effects, particularly when starting treatment or after dose increases. Other common digestive symptoms include stomach pain, decreased appetite, and constipation. These reactions typically improve as the body adapts to the medication.

How much weight can I lose in a month with Rybelsus?

Rybelsus is not approved by the FDA for weight loss. It is only authorized for type 2 diabetes management. However, Rybelsus can cause appetite suppression and induce a feeling of fullness, which can lead to weight loss. Results can depend on starting weight, diet, exercise habits, and individual response.

What foods should you avoid when taking Rybelsus?

When taking Rybelsus, minimize consumption of ultra-processed foods high in sugar, sodium, and unhealthy fats. Be cautious with spicy foods if experiencing digestive issues. Limit alcohol since it affects blood sugar levels. Instead, prioritize lean proteins, high-fiber fruits and vegetables, whole grains, and healthy fats for optimal blood sugar control. A registered dietitian can help you create a balanced diet that complements Rybelsus.

Find a diabetes dietitian near you, covered by insurance.

The views expressed by authors and contributors of such content are not endorsed or approved by Fay and are intended for informational purposes only. The content is reviewed by Fay only to confirm educational value and audience interest. You are encouraged to discuss any questions that you may have about your health with a healthcare provider.