The Side Effects of Rybelsus


Apr 23, 2024

Everything you need to know about oral Semaglutide and the possible side effects.

Woman reading on tablet
Woman reading on tablet
Woman reading on tablet

Are you one of the many people across the globe who have a phobia of needles?¹ While it’s easy to avoid heights, certain animals, escalators, or tiny spaces, needles are necessary in the medical field. By refusing needle injections, you could be facing serious health risks. 

For people who want to take Semaglutide but fear having to inject it, an oral form Semaglutide (Rybelsus®) or Compounded Semaglutide is a great option. While a majority of people take their Semaglutide medication in the subcutaneous injectable form, this special drug comes in a pill form. No needles, no pain, but all the benefits of Semaglutide.²

Interested in learning more about Rybelsus®? This guide describes everything you need to know about the benefits of oral Semaglutide and the potential side effects of this medication.

Oral Semaglutide

What is Rybelsus®? 

Rybelsus® is an oral, name-brand drug that consists of the active ingredient Semaglutide. Semaglutide is a medication that stimulates the pancreas to release insulin.² Semaglutide prescriptions are typically prescribed to people with Type 2 Diabetes, however, physicians have recently started recommending GLP-1 medications to weight management patients for off-label weight loss. 

Injectable Semaglutide and oral Semaglutide (like Rybelsus®) medications, as well as their compounded forms, can have different side effects due to their administration method. While both are used for off-label weight management, oral Semaglutide has some unique side effects that patients need to be aware of. 

How Oral Semaglutide Can Benefit You 

If you need insulin therapy to help manage your blood sugar levels or weight, it’s possible your healthcare provider may suggest a GLP-1 medication, like oral Semaglutide or Compounded Semaglutide, to help you maintain glycemic control. 

But before you take oral Semaglutide or Compounded Semaglutide, it’s important to know how this medication will benefit your body. Here’s what patients should expect when taking this prescription medication. 

Increased Insulin Production 

Not everyone produces the same amount of insulin. In fact, some individuals experience insulin resistance, where their body produces less insulin compared to others.³ Insulin resistance can be caused by genetics or an excess of body fat.³ 

Insulin helps the body absorb glucose from the bloodstream and store any excess within the liver and muscles.⁴ When you have extra glucose in the body, the pancreas will try to release more insulin to combat high blood sugar levels.⁵ However, after long periods of time, the pancreas begins to burn out — causing insulin resistance and excess glucose in the blood.⁵ 

Patients with Type 2 Diabetes have reduced insulin production compared to insulin demand.³ This puts people with Type 2 Diabetes at risk for hyperglycemia — otherwise known as high blood sugar levels.⁶ Having high blood sugar for extended periods can cause health risks like organ damage to the heart, eyes, kidneys, and nerves.⁶ 

Oral Semaglutide and Compounded Semaglutide can help increase insulin production to manage insulin resistance and Type 2 Diabetes and avoid the adverse effects of this disease.² 

Hyperglycemia Within Bloodstream

Delayed Gastric Emptying 

If you’re trying to lose weight or have been diagnosed with Type 2 Diabetes, it’s important to know about the various levels of glucose (or sugar) present in different foods. 

Simple carbohydrates, like soda, candy, and food containing corn syrup, will break down and digest quickly and produce higher amounts of glucose.⁴ However, healthy foods in the form of complex carbohydrates like brown rice, vegetables, and whole-grain foods, digest more slowly, taking longer to distribute glucose throughout the body.⁴ 

Oral Semaglutide and Compounded Semaglutide slow down digestion, referred to as delayed gastric emptying.⁷ With this medication, food is digested slower, allowing glucose to be distributed gradually and avoiding the drastic rise in blood sugar levels seen with simple carbohydrates.⁷ 

Possible Side Effects of Oral Semaglutide 

Just like any medication, Oral Semaglutide and Compounded Semaglutide have adverse effects that can affect individuals who take this drug. The majority of side effects can be avoided by people who follow administration guidelines and seek medical advice for severe problems. 

Here’s some mild side effects you may encounter when taking oral Semaglutide or Compounded Semaglutide, alongside other adverse side effects that require monitoring from a physician. 

#1: Interactions with Other Oral Medications 

When ingested, Semaglutide enters the stomach and causes delayed gastric emptying.⁷ Because oral Semaglutide causes slower digestion, it can interfere with the effectiveness of other medications.⁷ 

This can be problematic for people who have additional medications that need to be taken in the morning on an empty stomach.⁷ If you’re concerned about this possibility, be sure to discuss your treatment options with your prescribing physician. 

Since injectable Semaglutide is not digested through the stomach and enters the body immediately, this form of medication does not have the same risk of interacting with other oral medications. Learn more about injectable vs oral Semaglutide in this recent Henry Meds blog post.  

Woman ready to take pill with glass of water

#2: Hypoglycemia 

Although rare, hypoglycemia can occur if individuals taking oral Semaglutide are on additional insulin-stimulating medications.⁷ Hypoglycemia is a condition caused by low blood sugar levels. While mild hypoglycemia can be managed safely, severe hypoglycemia needs immediate medical attention.⁸ Untreated hypoglycemia can result in loss of consciousness, neurological damage, and, in severe cases, death.⁸ 

If you are taking Semaglutide in combination with another insulin-stimulating medication, it’s important to follow the dosage instructions as prescribed by your doctor to avoid interactions with other medications, hypoglycemia, and other adverse side effects.⁷ 

Rybelsus® and oral Semaglutide tablets require adults to wait 30 minutes before consuming food, drink, or additional pills.⁷ However, waiting longer than 30 minutes can cause increased absorption of oral Semaglutide. If you miss a daily dose by accident, skip the medication and continue your regimen as scheduled the next day.⁷

In addition to following the administration directions, discussing your current medications and concerns with your prescribing physician is crucial to avoid developing hypoglycemia. If you’re worried about possible interactions with other oral medicines or incorporating oral Semaglutide into your medication regimen, your healthcare provider may have other suggestions for GLP-1 prescriptions. 

Person Running on Treadmill

#3: Weight Loss 

Loss of appetite and delayed gastric emptying are two significant side effects of oral Semaglutide and Compounded Semaglutide, which is why some providers have prescribed this medication for weight management in patients.⁷

A recent clinical trial called OASIS 1 studied the effects of oral Semaglutide tablets on overweight and obese adults without Type 2 Diabetes.⁹ Only half of the participants were administered oral Semaglutide, but everyone received lifestyle interventions.⁹

After 68 weeks, the participants who received oral Semaglutide lost, on average, 15.1% of their body weight. This is a stark difference from the control group, who only lost 2.4% of their body weight through lifestyle interventions alone.¹⁰

Because Semaglutide and Compounded Semaglutide are known to reduce appetite, this medication has an effective off-label use for weight loss.⁷ 

Woman with Gastrointestinal Pain

#4: Gastrointestinal Side Effects 

One of the most common side effects of Semaglutide is gastrointestinal issues.⁷ This could include: 

  • Nausea

  • Vomiting

  • Abdominal Pain 

  • Diarrhea 

  • Constipation 

In the OASIS 1 study, 80% of participants taking oral Semaglutide reported some form of gastrointestinal issue during the 68-week study.⁹ However, the majority of participants who experienced abdominal problems indicated they were mild or moderate.⁹ Therefore, mild symptoms of gastrointestinal issues are fairly common for people taking oral Semaglutide. 

If you experience these adverse side effects and consider discontinuing the medication, talk to a healthcare provider to help minimize your symptoms. Your physician will review your administration routine and provide helpful advice to avoid significant gastrointestinal issues.

It’s important to note that your body will likely experience these gastrointestinal issues as it adjusts to the medication’s dosage, which usually takes about four weeks.⁷ Gastrointestinal symptoms may also be present when the dosage is increased.⁷ 

Rare Adverse Side Effects of Semaglutide 

While the following side effects are rare for adults with Type 2 Diabetes or weight management patients, it’s important to review for patients taking Semaglutide:⁷ 

Rare Side Effects of Oral Semaglutide
  • Diabetic Retinopathy is when individuals develop eye problems following their diabetes diagnosis. If you take Semaglutide, you have an increased chance of developing additional ocular complications.

  • At this time, Semaglutide research cannot confirm if the medication exaggerates symptoms of pancreatitis. Given the severity of this disorder, if you suspect that you have pancreatitis or have a confirmed diagnosis, you should not take oral Semaglutide. 

  • During the initial animal studies, oral Semaglutide was found to increase thyroid C-cell tumors in rodents. Therefore, individuals who have a history of thyroid cancer or other thyroid tumors such as medullary thyroid carcinoma should not take Semaglutide.

  • Gallbladder issues — including an inflamed gallbladder and gallstones — can be rare, yet urgent medical conditions that need immediate attention. While less than 2% of participants in an oral Semaglutide study experienced a gallbladder event, this side effect is important to take note of.¹⁰ 

While all of these side effects are rare, it’s important to keep an eye on your bodily reactions to prescription drugs. If you have any concerns about your blood sugar goals, it’s important to consult with a healthcare professional. 

Questions to Discuss with Your Healthcare Physician 

Once you have been approved for oral Semaglutide or Compounded Semaglutide treatment, you’ll want to review a few crucial pieces of information with your doctor. 

First, you’ll want to discuss administration guidelines and dosage instructions with your provider. Remember, oral Semaglutide has strict rules about when and how to take this prescription. 

Secondly, your physician will want to discuss your family history. If your history contains any blood relatives who struggle with pancreatitis, thyroid cancer, hypoglycemia, and more, your healthcare provider will want to discuss these issues in depth. 

Patient and Provider in Conversation

Semaglutide should not be taken by individuals who are pregnant or breastfeeding.⁷ If you’re planning on starting a family, you should discontinue medication 2 months prior. 

Remember, oral Semaglutide has the potential to cause drug interactions with other oral prescriptions.⁷ Be sure to disclose all your daily medications, including vitamins, so that your primary physician can provide medical advice on how to take these pills while on oral Semaglutide. 

Schedule a Telehealth Appointment with a Henry Meds Provider Today! 

Are you looking to find oral Compounded Semaglutide for weight management? Henry Meds has you covered. If you’re approved for treatment by the providers on the Henry Meds platform, you’ll only pay $297 for Compounded Semaglutide delivered straight to your door!

To help you trust the information we provide, every article written by Henry relies on peer-reviewed studies and medically-reviewed facts. We ensure that data, ideas, and figures cited are reliable, current, and accurate. Our team of medical reviewers aim to help you cut through the noise with clear and authoritative primary and secondary sources.

Nothing in this article is intended to be prescriptive or medical advice. Talk to your doctor before starting a new diet and exercise plan. Information presented is about our medically supervised weight management programs and is not an advertisement for a specific drug.

Please note: Henry Meds does not offer Ozempic® or Wegovy®, which are only available from the Novo Nordisk company. Compounded Semaglutide is a patient-specific medication created in a state Board of Pharmacy or FDA licensed compounding facility per a prescription from a licensed healthcare professional. Compounded drugs are required to exclusively use ingredients from FDA-licensed facilities, and test sterile compounds for potency, sterility, and purity. While compounded drugs are legal they do not undergo pre-market approval from the FDA as they are not made in large batches for the public, compounds are made based on specific orders from a medical professional. Because of that the dose, route of administration, safety, and efficacy may differ from commercially available, brand-name, drugs. Henry Meds exclusively works with licensed sterile compounding pharmacies in the United States.


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  2. Hughes, S., & Neumiller, J. J. (2020). Oral Semaglutide. Clinical diabetes : a publication of the American Diabetes Association, 38(1), 109–111. 

  3. Freeman, A. M., Acevedo, L. A., & Pennings, N. (2023). Insulin Resistance. In StatPearls. StatPearls Publishing. Retrieved from 

  4. Holesh, J. E., Aslam, S., & Martin, A. (2023). Physiology, Carbohydrates. In StatPearls. StatPearls Publishing. Retrieved from 

  5. Thota, S., & Akbar, A. (2023). Insulin. In StatPearls. StatPearls Publishing. Retrieved from 

  6. Mouri, M., & Badireddy, M. (2023). Hyperglycemia. In StatPearls. StatPearls Publishing. Retrieved from  

  7. U.S. Food and Drug Administration. (2019, September). Rybelsus (Semaglutide) Tablets. 

  8. Nakhleh, A., & Shehadeh, N. (2021). Hypoglycemia in diabetes: An update on pathophysiology, treatment, and prevention. World journal of diabetes, 12(12), 2036–2049. 

  9. Knop, F. K., Aroda, V. R., do Vale, R. D., Holst-Hansen, T., Laursen, P. N., Rosenstock, J., Rubino, D. M., Garvey, W. T., & OASIS 1 Investigators (2023). Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet (London, England), 402(10403), 705–719. 

  10. Smits, M. M., & Van Raalte, D. H. (2021). Safety of Semaglutide. Frontiers in endocrinology, 12, 645563. 

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