Rybelsus (semaglutide) is a prescription medication for adults with type 2 diabetes, aiming to improve blood sugar levels. It’s the first oral semaglutide product approved by the US Food and Drug Administration (FDA).

Rybelsus is available in 3 mg, 7 mg, and 14 mg tablets. It’s usually started at 3 mg once daily, increasing to 7 mg after 30 days and potentially to 14 mg thereafter for enhanced glycemic control.

As with any medication, Rybelsus may lead to certain side effects that individuals should be aware of. In 2023, poison control centers in the US received almost 3,000 calls related to semaglutide, with inquiries mainly about its side effects.

Understanding these effects can help individuals make informed decisions about their treatment and better manage any adverse reactions they may experience. Let’s explore the side effects of this popular diabetes medication in more detail.

Key Findings

  • Nausea, abdominal pain, diarrhea, decreased appetite, vomiting, and constipation are common side effects of Rybelsus, often easing within a few days or weeks.
  • Rare but serious side effects of Rybelsus include pancreatitis, hypoglycemia, kidney problems, allergic reactions, and gallbladder issues.
  • Monitoring for thyroid C-cell tumors, diabetic retinopathy complications, increases in amylase and lipase, and potential drug interactions is important during treatment.
  • Precautions for Rybelsus include monitoring for thyroid C-cell tumors, diabetic retinopathy complications, increases in amylase and lipase, and potential drug interactions.
  • Strategies for managing side effects include dietary adjustments, hydration, physical activity, stress management, and monitoring blood sugar levels.
  • Lifestyle modifications such as regular exercise and a balanced diet can support Rybelsus treatment.

What are the Side Effects of Rybelsus?

Outlined below is the range of potential side effects associated with Rybelsus use.

Common Side Effects of Rybelsus

The side effects listed below are from two studies involving patients with type 2 diabetes (T2D) who received Rybelsus or a placebo. Kidney function assessments at baseline showed that most patients had normal function, with some having mild or moderate impairment.

These adverse reactions occurred in at least 5% of patients treated with Rybelsus.

  • nausea
  • abdominal pain
  • diarrhea
  • decreased appetite
  • vomiting
  • constipation

Gastrointestinal issues are a common side effect, such as nausea, vomiting, and diarrhea, are common when starting Rybelsus or increasing the dose as the body adjusts to the medication. For most individuals, these side effects typically diminish within a few days or weeks.

Other gastrointestinal side effects associated with Rybelsus 7 mg and 14 mg doses are as follows:

  • abdominal distension
  • dyspepsia (indigestion)
  • eructation (burping)
  • flatulence (gas)
  • gastroesophageal reflux disease (GERD)
  • gastritis (inflammation of the stomach lining)

Additionally, other studies that studied the safety and efficacy of Rybelsus reported the following adverse events:

  • nasopharyngitis
  • influenza
  • headache
  • decreased appetite
  • upper respiratory tract infection
  • hypertension
  • back pain
  • urinary tract infection
  • arthralgia (joint pain or discomfort)

These side effects usually don’t last long and may be effectively addressed.

Serious Side Effects of Rybelsus

Serious side effects of Rybelsus are rare but possible. These include:

  • Pancreatitis (inflammation of the pancreas): Persistent severe abdominal pain, which might extend to the back and could be accompanied by vomiting, could indicate pancreatitis.
  • Hypoglycemia (low blood sugar): Patients who are taking Rybelsus along with insulin or sulfonylurea drugs may face a higher likelihood of experiencing hypoglycemia, including severe episodes. Symptoms may include:
    • shakiness or tremors
    • sweating
    • fast heartbeat
    • dizziness or lightheadedness
    • weakness or fatigue
    • irritability or mood changes
    • hunger
    • blurred vision
    • tingling or numbness in lips, tongue, or cheeks
    • headache
    • confusion or difficulty concentrating
  • Kidney problems: The gastrointestinal side effects of Rybelsus can lead to dehydration, which could worsen kidney issues, particularly in patients who already have existing kidney problems. It may manifest as:
    • dark urine
    • urinating less than usual or not at all
    • swelling in the feet, ankles, or hands
    • confusion
  • Serious allergic reactions: Severe allergic reactions, such as anaphylaxis or angioedema, have been documented in patients using Rybelsus. If any signs of hypersensitivity occur, stop Rybelsus usage immediately. Symptoms may include:
    • facial, lip, tongue, or throat swelling
    • breathing or swallowing difficulties
    • severe rash or itching
    • fainting or dizziness
    • rapid heartbeat
  • Gallbladder problems: Symptoms of gallbladder problems may manifest as:
    • pain in the upper abdomen
    • yellowing of the skin or eyes (jaundice)
    • fever
    • clay-colored stools

Some of these might become noticeable only after prolonged use or extended exposure to the medication.


The Food and Drug Administration (FDA) monitors and evaluates a medication’s side effects. If you wish to report a side effect experienced with Rybelsus to the FDA, you can do so by visiting MedWatch.

Precautions for Rybelsus

The use of Rybelsus comes with certain risks and precautions that should be considered:

  • Risk of Thyroid C-Cell Tumors: Semaglutide has been associated with an increased risk of thyroid C-cell tumors in animal studies. It is unknown whether Rybelsus increases the risk of these tumors in humans. Still, caution should be exercised, especially in patients with a history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2)Symptoms suggestive of thyroid cancer may include:
    • persistent hoarseness
    • presence of a lump in the throat
    • difficulty swallowing
    • shortness of breath
  • Diabetic Retinopathy Complications: Rapid improvement in glucose control, such as with Rybelsus or semaglutide injection, can temporarily worsen diabetic retinopathy. However, the long-term impact of glycemic control with semaglutide on diabetic retinopathy complications has not been thoroughly studied. Patients with a history of diabetic retinopathy should be closely monitored for any progression of the condition.
  • Increases in Amylase and Lipase: An elevation in amylase and lipase levels, as seen in Rybelsus trials, could signal pancreatic issues. While minor increases might not pose a threat, persistent or substantial elevations could suggest pancreatitis.
  • Drug Interactions: According to Drugs.com, there are 251 drugs known to interact with Rybelsus (semaglutide). Among these interactions, two are considered major, 248 are moderate, and one is minor. Examples are:
  • dexamethasone ophthalmic
  • albuterol
  • amprenavir
  • atazanavir
  • betamethasone
  • bumetanide
  • ciprofloxacin
  • clarithromycin
  • dexfenfluramine
  • dopamine
  • epinephrine
  • fenfluramine
  • fluticasone topical
  • glipizide
  • insulin
  • levothyroxine
  • niacinamide
  • orlistat
  • ritonavir
  • salmeterol
  • bexarotene
  • gatifloxacin

How to Minimize Side Effects

Here are some strategies to alleviate potential discomfort with Rybelsus treatment:

Nausea, Vomiting, and Diarrhea

To address these side effects while taking Rybelsus, it’s important to drink plenty of fluids. Sipping on ice-cold beverages can be soothing for nausea, while soups and broths can replenish lost electrolytes such as sodium and potassium due to vomiting and diarrhea.

Additionally, you consider the following tips:

  • Stick to bland, low-fiber foods such as bananas, rice, applesauce, and toast (BRAT diet) to help firm up stools and ease digestion.
  • Opt for foods with high water content, such as soups and gelatin.
  • Steer clear of fried, greasy, or sugary foods.
  • Refrain from lying down immediately after eating.
  • Go outdoors for fresh air.
  • Enjoy smaller, more frequent meals.

2. Constipation

Constipation is another gastrointestinal side effect that can result from dehydration. It refers to difficulty passing stools or infrequent bowel movements, often resulting in hard, dry stools. Here are general tips on managing constipation:

  • Drink plenty of fluids, especially water, to help soften stools and promote bowel movements.
  • Increase your intake of dietary fiber to promote regular bowel movements.
  • Engage in regular physical activity to stimulate bowel function and improve digestive motility.
  • Try to establish a regular bowel movement routine.

3. Abdominal Pain

Here are some general tips on managing abdominal pain:

  • Keep a food diary to track your diet and identify triggers for abdominal pain.
  • Avoid spicy, fatty, dairy (if lactose intolerant), and high-fiber foods if you have digestive conditions like IBS.
  • Choose smaller, more frequent meals throughout the day.
  • Manage stress with techniques like deep breathing, meditation, yoga, or regular exercise to reduce abdominal pain.
  • Use a heating pad or warm compress on your abdomen to relax muscles and ease discomfort.

Note that persistent abdominal pain, especially if radiating to the back and accompanied by vomiting, can be a sign of pancreatitis. If you experience these symptoms, contact your doctor immediately for evaluation and appropriate management.

4. Decreased Appetite and Weight Loss

If you have type 2 diabetes, weight loss typically benefits your blood sugar levels and overall health. However, the digestive side effects of Rybelsus, such as diarrhea and vomiting, can lead to reduced appetite and unintended weight loss. Losing weight solely due to these side effects isn’t ideal for your health.

Consider eating smaller, more frequent meals throughout the day to maintain adequate nutrition despite a decreased appetite. Prioritize nutrient-dense foods high in protein, vitamins, and minerals to meet your body’s essential needs.

5. Headache

Make sure you drink enough water during the day to stay hydrated, as dehydration can sometimes cause headaches. You can also try over-the-counter pain relievers, but talk to your healthcare provider first.

6. Upper Respiratory Tract Infections

Practice good hygiene habits, such as frequent handwashing with soap and water, to reduce your risk of contracting upper respiratory tract infections. Avoid close contact with individuals who are sick, and consider wearing a mask in crowded or high-risk settings.

7. Gastroesophageal Reflux Disease (GERD)

GERD is a persistent digestive condition that involves stomach acid flowing back into the esophagus, leading to discomfort like heartburn and chest pain. Acid reflux often signals GERD. To manage acid reflux while on Rybelsus, consider these tips:

  • Opt for frequent, smaller meals over larger ones.
  • Steer clear of spicy and greasy foods.
  • Refrain from lying down right after eating.
  • Improve posture by sitting and standing straight.
  • Elevate the head of your bed if nighttime symptoms worsen.

If these steps aren’t effective, over-the-counter options may provide relief. These include antacids like Tums or Rolaids, alginate-containing antacids like Gaviscon, H2 blockers like Pepcid, and proton pump inhibitors like Nexium.

If acid reflux persists beyond two weeks, consult your healthcare provider for further evaluation.

8. Hypoglycemia (Low Blood Sugar)

Monitor your blood sugar levels regularly, especially when starting Rybelsus treatment or adjusting your dosage. Always have fast-acting glucose nearby. This could be glucose tablets, juice, or hard candy. Use these to raise your blood sugar levels quickly if hypoglycemia happens. You may also want to wear a medical alert bracelet.

Lifestyle Changes to Support Rybelsus Treatment

To maximize the benefits of Rybelsus, incorporate regular exercise and a well-rounded diet into your lifestyle. Here are some practical lifestyle adjustments to complement your Rybelsus treatment:


Here are tips for dietary management while taking Rybelsus:

  • Incorporate fresh whole fruits, vegetables, beans and legumes, whole grains like brown rice, and low- or non-fat dairy products into your diet. Replace sugar-sweetened beverages with fresh water.
  • Consider following low-fat, low-carbohydrate, Mediterranean, or vegetarian diets. Discuss with your doctor before starting any diet, as they may not suit everyone.
  • Avoid trans fats and saturated fats found in whole milk, butter, fried foods, cheese, full-fat dairy products, and processed meats. Instead, opt for healthier fats like those in fish, olive oil, and nuts.
  • Limit your consumption of red meat and opt for lean protein sources such as lean chicken, turkey, fish, eggs, beans, soy, and nuts.
  • Increase fiber intake by choosing whole grains over highly processed white bread, pasta, and rice. Opt for brown rice, whole grain bread, and pasta options, which also provide added fiber.

Regular Physical Activity

Staying active when you have diabetes boosts your body’s sensitivity to insulin, aiding in blood sugar management and reducing the risk of heart disease and nerve damage. Additional benefits include:

  • weight management
  • improved mood
  • better sleep
  • enhanced memory
  • blood pressure control
  • cholesterol balance (lowering low-density lipoprotein or “bad” cholesterol and raising high-density lipoprotein or “good” cholesterol)

The Centers for Disease Control and Prevention (CDC) recommends aiming for at least 150 minutes of moderate-intensity physical activity per week, which translates to 20 to 25 minutes of activity daily.

Examples include:

  • brisk walking
  • doing housework
  • mowing your lawn
  • dancing or Zumba
  • swimming
  • cycling
  • sports participation

These activities work your large muscles, increase your heart rate, and make you breathe harder, which are important goals for fitness. Stretching helps to make you flexible and prevent soreness after being physically active.

Stress Management Techniques

Managing diabetes can be stressful, and stress can impact blood sugar and insulin levels. Learning to handle stress effectively may help maintain blood sugar control.

The American Diabetes Association (ADA) suggests these stress management techniques:

  • Focus on the present moment to avoid worries.
  • Break tasks into smaller steps and take immediate action.
  • Use deep breathing exercises to calm the nervous system.
  • Create a meaningful phrase to guide you through stressful situations.
  • Visualize a peaceful setting and engage your senses.
  • Maintain a gratitude journal to boost overall well-being.
  • Indulge without guilt and make adjustments for balance.
  • Enjoy a soothing bath or shower for relaxation and better sleep.


The effects of Rybelsus can differ from person to person. Common side effects include nausea, vomiting, diarrhea, reduced appetite, and stomach discomfort. There are also less common side effects like low blood sugar, headaches, and respiratory infections.

Although rare, more serious side effects such as pancreatitis, allergic reactions, kidney problems, and gallbladder issues can occur.

Communication with your doctor throughout Rybelsus treatment is vital for personalized, effective, and safe management of type 2 diabetes. This collaboration helps patients achieve treatment goals and maintain overall well-being.

Frequently Asked Questions

Do Rybelsus side effects go away?

In many cases, yes. In particular, gastrointestinal side effects like nausea, vomiting, and diarrhea often improve over time as the body adjusts to the medication. However, some side effects may persist or require medical attention. In this case, it is important to discuss any concerns with your healthcare provider, who can offer guidance and support.

How long do Rybelsus side effects last?

The duration can vary from person to person. For some individuals, side effects like gastrointestinal discomfort may improve or resolve within a few days to weeks. In some cases, individuals may need to change their treatment plan altogether to better manage side effects or achieve optimal results.

Can you take Rybelsus every other day?

The dosing schedule for Rybelsus is once daily and is recommended to be taken at the same time each day. Intentionally skipping a day may not lead to the desired treatment results.

How long does Rybelsus stay in your system?

Semaglutide remains in your system for approximately 4 to 5 weeks after the last dose.

How long does it take for Rybelsus to start working?

After taking Rybelsus, semaglutide levels peak in the blood about one hour later. With regular dosing, it takes approximately 4 to 5 weeks for semaglutide to remain consistent in the blood without significant fluctuations. While some people may begin to experience blood sugar management effects within 30 days of starting Rybelsus, significant improvements often take several months to become apparent. Clinical studies have indicated that after 26 weeks of treatment, individuals taking Rybelsus achieved an HbA1c level of less than 7%.

How often do you take Rybelsus?

Rybelsus is available in tablet form and should be taken orally once daily.

What happens when you stop taking Rybelsus?

When you stop taking semaglutide, your body will go through a process of re-regulation, which may cause rebound effects and other symptoms of withdrawal.

When is the best time to take Rybelsus?

Rybelsus is recommended to be taken at least 30 minutes before your first meal.

Why does Rybelsus cause nausea?

Rybelsus can cause nausea as a side effect due to its mechanism of action, especially how it affects the gastrointestinal system. Semaglutide, the active ingredient in Rybelsus, works by mimicking the function of a hormone called glucagon-like peptide-1 (GLP-1), which helps regulate blood sugar levels. GLP-1 receptors are found in various body parts, including the stomach and brain. Activation of these receptors can lead to decreased appetite and slowed gastric emptying, which may contribute to feelings of nausea.

Is Rybelsus safe to take for weight loss?

Rybelsus is not FDA-approved for weight loss purposes. It is specifically indicated for treating type 2 diabetes mellitus to improve glycemic control in adults. However, Rybelsus is occasionally prescribed off-label for weight loss. It should only be used for this purpose under the guidance and supervision of a healthcare professional.

Can you just stop taking Rybelsus?

Yes, but only if you and your healthcare provider determine that Rybelsus isn’t suitable or beneficial. For instance, if you experience a severe adverse reaction to Rybelsus, your healthcare provider may advise you to cease taking it immediately. A possible example is pancreatitis.

What are the side effects of stopping Rybelsus?

When you discontinue Rybelsus, which contains the active ingredient semaglutide, withdrawal symptoms often manifest as rebound effects due to decreased GLP-1 activity. These withdrawal symptoms may include increased appetite, decreased feelings of fullness (satiety), rise in blood sugar levels, weight gain, and cardiovascular changes such as elevated blood pressure.

Can Rybelsus cause hair loss?

No. Hair loss wasn’t documented as a side effect in clinical trials of Rybelsus. However, hair loss can be associated with diabetes. It’s considered a symptom of both type 1 and type 2 diabetes. It is believed to stem from various factors like hormonal imbalances, impaired circulation due to high blood sugar levels, or autoimmune issues. Fortunately, addressing these underlying causes and controlling blood sugar levels can often reverse hair loss, sometimes with the help of medications.

Can Rybelsus make you tired?

No. Tiredness wasn’t reported as a side effect of Rybelsus. However, not eating enough nutrient-dense calories during the treatment can cause fatigue or low energy levels.

What are the long-term side effects of semaglutide?

Most long-term effects of semaglutide are rare. These can include kidney damage, pancreatitis, gallbladder complications, and diabetic retinopathy. If you experience any symptoms related to these conditions, it’s important to consult your doctor promptly for proper evaluation and management.

What are the side effects of Rybelsus in the elderly?

Side effects in elderly patients do not differ significantly from those observed in younger age groups. In some clinical trials, a significant number of participants were elderly, aged 65 years or older, with some even reaching 75 years and older. For instance, in the PIONEER 6 trial, 56% of Rybelsus-treated patients were 65 years and older, while 12.6% were 75 years and older. Despite this higher representation of older individuals, no substantial differences were observed compared to younger age groups. However, it’s worth noting that although no overall variations in safety or efficacy were detected, the possibility of heightened sensitivity in some elderly individuals cannot be completely ruled out. Therefore, healthcare providers should remain vigilant and consider potential age-related factors when prescribing Rybelsus to older patients.

Are there any long-term side effects of Rybelsus treatment?

While rare, some long-term effects of Rybelsus may comprise kidney issues, pancreatitis, complications with the gallbladder, and diabetic retinopathy. If you observe any signs suggestive of these conditions, consult your doctor immediately.


Aroda, V.R., et. al. (2019, Jun). PIONEER 1: Randomized Clinical Trial of the Efficacy and Safety of Oral Semaglutide Monotherapy in Comparison With Placebo in Patients With Type 2 Diabetes. American Diabetes Association.


Rodbard, H.W., et. al. (2019, Oct). Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 Trial. American Diabetes Association.


Rosenstock, J., et. al. (2019, Mar). Effect of Additional Oral Semaglutide vs Sitagliptin on Glycated Hemoglobin in Adults With Type 2 Diabetes Uncontrolled With Metformin Alone or With Sulfonylurea. JAMA Network. https://jamanetwork.com/journals/jama/fullarticle/2729339

Pratley, R., et al. (2019, Jul). Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial. The Lancet.


Mosenzon, O., et. al. (2019, Jul). Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial. The Lancet.


Medicine Matters. (2019, Jul). A quick guide to the PIONEER trials. Retrieved from


FDA. (2021, Apr). Highlights Of Prescribing Information of Rybelsus. Retrieved from


Benadjaoud, Y., et. al. (2023, Dec). Poison control centers report increase in calls related to drugs used for weight loss. ABC News. https://abcnews.go.com/GMA/Wellness/poison-control-centers-report-increase-calls-related-drugs/story?id=105685860