Does Rybelsus make you feel bad? An in-depth look at side effects

October 10, 2025 •

5 min read

In studies, up to 41% of patients receiving Rybelsus experienced stomach side effects, compared to 21% taking a placebo. It is not uncommon for Rybelsus to cause side effects that can make you feel unwell, especially when starting the medication.

Quick Summary

This article explores the common and serious side effects of Rybelsus, a medication for type 2 diabetes. Learn what to expect when starting treatment, how long side effects typically last, and practical strategies for managing gastrointestinal and other symptoms. The guide also covers important safety information and when to contact a doctor.

Key Points

Initial Side Effects Are Common: Many patients experience gastrointestinal side effects like nausea and diarrhea, especially when first starting Rybelsus or increasing the dose.
Gastrointestinal Issues Often Fade: For most, these digestive problems are temporary and lessen as your body adjusts to the medication over a few weeks.
Dosage Matters: Higher doses of Rybelsus can increase the likelihood and severity of digestive side effects.
Management is Possible: Dietary changes, such as eating smaller, low-fat meals, and staying hydrated can help mitigate common side effects.
Serious Side Effects Exist: Though rare, risks like pancreatitis, kidney issues, and low blood sugar (especially when combined with other medications) require immediate medical attention.
Thyroid Cancer Risk: Rybelsus carries a boxed warning regarding the risk of thyroid tumors, and should be avoided by individuals with a specific history of thyroid cancer or MEN2.
Follow Dosing Strictly: Taking Rybelsus as directed, on an empty stomach with a small amount of water, is critical for proper absorption and to minimize side effects.

What to Expect When Starting Rybelsus

Rybelsus (semaglutide) is an oral medication approved for managing blood sugar in adults with type 2 diabetes. As a glucagon-like peptide-1 (GLP-1) receptor agonist, it works by mimicking a natural hormone that helps increase insulin production, reduce glucose from the liver, and slow down digestion. This delayed gastric emptying is a key reason for many of the initial side effects that can make some patients feel bad. Your doctor will typically start you on a lower dose and gradually increase it, which helps your body adjust and minimizes the severity of these symptoms. Most common side effects tend to occur early in treatment or after a dose increase and usually improve over time.

Common Side Effects and Management

The most commonly reported side effects of Rybelsus are digestive in nature and are the primary reason some people feel unwell.

Nausea: This is the most frequent side effect, affecting a significant number of users, particularly at the beginning of treatment or after a dose adjustment.
Diarrhea and Constipation: While Rybelsus can cause both, diarrhea is slightly more common and often temporary as your body adjusts. Staying hydrated is key to managing diarrhea.
Abdominal Pain: Discomfort, cramps, or bloating in the stomach area are often reported. Eating smaller, more frequent meals can help reduce this.
Decreased Appetite and Vomiting: Many people experience a reduced appetite, which can lead to weight loss. Vomiting can also occur, especially if nausea is severe. If vomiting persists, it can lead to dehydration.
Other Mild Side Effects: Some patients may experience less common issues like headache, fatigue, dizziness, belching, gas, and acid reflux. Fatigue may be related to decreased food intake or fluctuations in blood sugar.

Tips for Managing Side Effects

If you experience common side effects, these simple strategies may offer relief:

Modify Your Diet: Eat bland, low-fat foods like rice, crackers, and toast. Avoid fried, greasy, spicy, or high-sugar foods that can aggravate the stomach.
Adjust Meal Habits: Eat smaller, more frequent meals throughout the day instead of three large ones. Eat more slowly to aid digestion.
Stay Hydrated: Drink plenty of clear fluids, especially if experiencing vomiting or diarrhea, to prevent dehydration. Avoid carbonated beverages.
Wait Before Lying Down: Don't lie down immediately after eating, which can worsen nausea or acid reflux.
Follow Dosing Instructions: Take Rybelsus first thing in the morning on an empty stomach with a small sip of plain water, waiting at least 30 minutes before eating or taking other oral medications. Not following these instructions can impact absorption and effectiveness.

Comparison of Rybelsus and Ozempic Side Effects

Both Rybelsus and Ozempic contain the same active ingredient, semaglutide, but are administered differently: Rybelsus is an oral tablet, while Ozempic is an injectable. Consequently, they share many similar side effects, though the severity and frequency can differ.


Side Effect	Rybelsus (Oral)	Ozempic (Injectable)	Notes
Gastrointestinal	High incidence, especially when starting or increasing dose.	High incidence, similar profile to Rybelsus.	Both can cause significant nausea, vomiting, and diarrhea.
Injection Site	Not applicable.	Possible swelling, redness, or itching at injection site.	Only applies to injectable form, Ozempic.
Systemic	Headache, fatigue, dizziness are possible.	Headache, fatigue, dizziness are possible.	These are not uncommon with semaglutide.
Severe	Pancreatitis, thyroid cancer risk (boxed warning), kidney issues, hypoglycemia.	Pancreatitis, thyroid cancer risk (boxed warning), kidney issues, hypoglycemia.	Both carry similar rare but serious risks.

Serious and Less Common Side Effects

While less frequent, Rybelsus carries a risk of serious side effects that require immediate medical attention. It's crucial to be aware of these and contact your doctor if they occur.

Boxed Warning for Thyroid Tumors: Rybelsus has a boxed warning from the FDA regarding a risk of thyroid C-cell tumors, observed in rodent studies. Patients with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN2) should not use Rybelsus. Symptoms to watch for include a lump or swelling in your neck, hoarseness, trouble swallowing, or shortness of breath.
Pancreatitis: Inflammation of the pancreas is a rare but serious risk. If you experience severe, persistent abdominal pain with or without vomiting, stop taking Rybelsus and contact your doctor immediately.
Kidney Problems: In rare cases, Rybelsus can cause new or worsening kidney problems. Severe vomiting or diarrhea can lead to dehydration, which increases this risk. Symptoms include decreased urination, swelling in your ankles or feet, or fatigue.
Hypoglycemia (Low Blood Sugar): The risk of low blood sugar is higher when Rybelsus is taken with other diabetes medications like insulin or sulfonylureas. Symptoms include dizziness, shakiness, sweating, confusion, and a fast heart rate.
Allergic Reactions: Though uncommon, severe allergic reactions can occur. Seek immediate medical help if you experience swelling of the face, lips, or tongue, trouble breathing, or a severe rash.

How Long Do Side Effects Last?

For most people, the common gastrointestinal side effects are temporary and subside within a few days to several weeks as the body gets used to the medication. When your doctor increases your dosage, these side effects may reappear briefly before fading again. If side effects are persistent, severe, or do not improve, it's important to discuss options with your doctor. While Rybelsus is intended for long-term use, there are currently no known long-term side effects associated with its prolonged use once initial acclimation has occurred.

Conclusion

While many people tolerate Rybelsus well, some will experience side effects that can make them feel bad, particularly during the initial phase of treatment. The most common issues are digestive, such as nausea, abdominal pain, and changes in bowel habits, which are largely due to the medication's effect of slowing down gastric emptying. Fortunately, these symptoms often improve over time as your body adjusts. Serious side effects are rare, but awareness of their signs is essential. By following dosing instructions, making dietary adjustments, and communicating openly with your healthcare provider, you can effectively manage most side effects and ensure your treatment is both safe and successful.

Disclaimer: The information provided in this article is for informational purposes only and does not constitute medical advice. Consult with a qualified healthcare provider for any health concerns or before making decisions related to your treatment.

Frequently Asked Questions

The most common side effects of Rybelsus are digestive in nature and include nausea, abdominal pain, diarrhea, decreased appetite, vomiting, and constipation. These effects are often most noticeable when you first begin treatment.

For most people, the common, mild side effects like nausea and diarrhea are temporary and improve within a few days to weeks as your body adjusts to the medication. If your dose is increased, side effects may return briefly before subsiding again.

It's unlikely for Rybelsus to cause long-term side effects that last indefinitely. In clinical studies, no long-term side effects were reported. Most adverse effects are temporary and resolved either during or after stopping treatment.

Yes, but you should inform your doctor about all other medications you take, including over-the-counter drugs and supplements, as Rybelsus can interact with them. In particular, using Rybelsus with insulin or sulfonylureas increases the risk of hypoglycemia (low blood sugar).

Yes, the dose can affect your risk of side effects. Studies have shown that some gastrointestinal effects, like nausea and vomiting, are more common with higher doses (e.g., 14 mg) compared to lower doses (e.g., 7 mg).

Tiredness was not reported as a side effect in clinical studies. However, some users have anecdotally reported feeling tired. This might be linked to a reduced caloric intake due to a decreased appetite or other side effects like digestive issues affecting sleep.

You should contact your doctor if your common side effects are severe, persistent, or become bothersome. Seek immediate medical attention if you experience signs of serious side effects, such as a lump in your neck, severe abdominal pain, vision changes, or an allergic reaction.