What you’ll learn:
- Rybelsus® is the first oral GLP-1 medication approved for type 2 diabetes and may also support weight loss when prescribed off-label.
- Most people experience mild side effects like nausea or constipation, which often improve with dose adjustments and time.
- Though rare, serious side effects like pancreatitis, gallbladder issues, and thyroid concerns can occur and should be discussed with your provider.
Rybelsus® is a unique medication. It’s the first oral GLP-1 medication FDA-approved for type 2 diabetes, setting it apart from the rest of the medications in that class that are injected. Like Ozempic®, Rybelsus contains semaglutide and can manage blood sugar or be prescribed off-label for weight loss.
Because it contains semaglutide, like Ozempic® and Wegovy®, it tends to cause similar side effects, though it is absorbed differently, having to pass through the digestive system to get into the body. The most common symptoms people experience are gastrointestinal, like nausea, constipation, and vomiting.
Like all other GLP-1 medications, Rybelsys follows a step-up dosing approach called titration, which means the dose increases slowly over time. This gradual increase gives your body time to adjust and can help minimize side effects while maximizing the medication’s benefits. Since your experience can vary based on how quickly you increase your dose, we’ll explain exactly how Rybelsus® titration works.
Rybelsus® comes with a low risk of serious side effects, such as pancreatitis or gallbladder issues. Though rare, we’ll cover what to keep an eye on and when it’s a good idea to check in with your doctor.
How Rybelsus® affects your body
The semaglutide in Rybelsus® mimics GLP-1, a hormone your body naturally makes, primarily after eating. It helps your pancreas release insulin when your blood sugar is high and tells your liver to ease up on releasing stored sugar. At the same time, it reduces appetite and slows how quickly food leaves your stomach, which can help you feel full longer and reduce spikes in blood sugar.
This combination helps manage hunger and control blood sugar, which can lead to gradual weight loss. Eating less often feels easier because your body isn’t sending as many “I’m hungry” signals.
But these same actions, especially the slowed digestion, can trigger side effects like nausea, bloating, constipation, or vomiting, particularly when you first start taking it or increase your dose. Your digestive system needs time to adjust to the slower pace, which is why Rybelsus® is started at a low dose and gradually increased. Adjusting how and what you eat can also help your body better handle the medication’s effects on digestion and appetite.
When Rybelsus® side effects are most likely
Side effects are most likely to appear in the first few weeks, especially when you start he medication or your dose increases. Rybelsus® step-up dosing schedule is designed to help your body adjust and minimize side effects. Everyone starts with 3 mg for the first month before moving to 7 mg, and possibly 14 mg later if you need more blood sugar support. If you get the benefits you want and minimal to no side effects, increasing your dose is unnecessary.
Common side effects of Rybelsus®
Rybelsus® can help with blood sugar control and may support weight management (off-label), but your body may need some time to adjust to the semaglutide, especially since your daily habits will also be adjusting. Upset stomach, nausea, and other digestive changes are common when starting.
The good news is that these side effects often get easier to manage as your body gets used to the medication. Your diet and exercise routines can also help you manage these effects, and maintaining healthy habits in these areas will also help you manage your blood sugar or support weight loss, depending on your goals.
Gastrointestinal symptoms
Digestive changes are the most frequent side effects people notice with Rybelsus®. The table below highlights reported rates of these effects in clinical trials with the 7 mg and 14 mg doses, along with tips that may help ease them:
| Symptom | 7 mg | 14 mg | What can help |
|---|---|---|---|
| Nausea | 11% | 20% | Eating smaller, lower-fat meals may ease nausea. |
| Abdominal pain | 10% | 11% | Focus on staying hydrated with clear fluids. |
| Diarrhea | 9% | 10% | Focusing on hydration and choosing low-fiber foods can help you recover from diarrhea. |
| Vomiting | 6% | 8% | Sip clear liquids and stick to bland food like crackers until your stomach settles. |
| Constipation | 6% | 5% | Drinking more water, slowly increasing fiber intake, and getting regular physical activity can help. |
Other symptoms
Beyond digestive symptoms, Rybelsus® can sometimes lead to other side effects. Again, these tend to occur early in treatment and often ease as your body adapts. Here’s what some people have experienced:
- Increased heart rate: Clinical trials showed that Rybelsus® can raise resting heart rate by 1 to 3 beats per minute. This increase is usually mild but may be monitored more closely in people with existing heart conditions.
Other potential side effects of Rybelsus®
Some side effects linked to semaglutide treatments—like Ozempic®, Wegovy®, and Rybelsus®—may be related more to weight loss than the medication itself. These effects tend to be more noticeable with injectable forms, since they typically lead to greater weight loss than Rybelsus®.
| Potential side effects | Why it happens | What to do according to healthcare experts |
|---|---|---|
| Muscle loss or loss of muscle tone | Weight loss without strength training can reduce lean muscle mass, especially at higher doses. | Eat enough protein and include resistance training to help preserve muscle. |
| Facial volume loss | Fat loss in the face can create a more sunken look, though this is more often associated with injectables. | Stay hydrated and aim for gradual, steady weight loss. |
| Depression | Emotional changes have been reported but aren’t well understood. | Track how you’re feeling and speak to a provider if something feels off. Call 988 if you need immediate mental health support. |
Not everyone taking Rybelsus® will experience these side effects, but knowing what’s possible can help you feel more prepared. If something feels off, your healthcare provider can help you explore what’s going on and recommend next steps.
Side effects of stopping Rybelsus®
Rybelsus® is designed for ongoing use to help manage blood sugar and weight. Stopping suddenly could lead to your blood sugar levels rising again and a return of hunger over time. Here are a few things to keep in mind:
- Blood sugar may increase: Rybelsus® helps lower blood sugar, so stopping it may cause levels to go back up, especially if no other treatment is in place.
- Weight regain is possible: Stopping Rybelsus® may lead to weight gain if healthy habits aren’t continued. Staying active and eating well can help maintain progress.
- Tapering might not be required: Unlike some other medications, Rybelsus® doesn’t typically require a slow taper, but your provider may recommend a plan based on your health needs.
If you’re considering stopping Rybelsus®, talk with your healthcare provider first. They can help you decide on the safest way to adjust your treatment.
Rybelsus side effects in females
Semaglutide medications like Rybelsus® don’t cause side effects that are specific to females, but some experiences may be more common due to hormonal changes or how weight loss affects the body. Here’s what to know:
- Polycystic ovarian syndrome (PCOS) benefits: Some research shows nearly 80% of people with PCOS and a BMI of 30 or higher noticed more regular periods after six months of semaglutide treatment.
- Higher sensitivity to side effects: According to research, females may be more likely to report nausea, vomiting, or digestive issues when using GLP-1 medications like Rybelsus®.
- Cycle changes: Rapid weight loss or hormone shifts while taking semaglutide medications like Rybelsus® may lead to temporary changes in your cycle, such as irregular periods or spotting.
- Fertility changes: Weight loss can improve ovulation and may make pregnancy more likely, but Rybelsus® isn’t a fertility treatment. It should be stopped at least two months before trying to conceive.
- Birth control considerations: Because GLP-1 medications like Rybelsus® may slow digestion, it could affect how oral birth control pills are absorbed. Using a non-pill option or backup method may help.
If you experience cycle changes or are planning for pregnancy, talk with your healthcare provider. They can help you make a safe plan based on your needs.
Severe side effects and warnings associated with Rybelsus®
While Rybelsus® is generally a well-tolerated medication, it does come with some risks. Serious side effects are rare, but knowing what to watch for can help you respond quickly if something feels off.
Rybelsus® carries an FDA boxed warning about a possible risk of thyroid C-cell tumors based on animal studies. It’s not known if this applies to people, but you should avoid Rybelsus® if you or a family member has a history of medullary thyroid carcinoma (MTC) or MEN 2. Be sure to share this with your provider before starting treatment.
Here are some other potential rare side effects. If you experience any signs of these, get immediate medical attention:
- Pancreatitis: Ongoing stomach pain that spreads to your back, especially with nausea or vomiting, could signal pancreatitis. Stop the medication and get medical care right away.
- Gallbladder issues: Pain in the upper right abdomen, fever, nausea, or yellowing of the skin or eyes may point to gallstones or gallbladder inflammation.
- Kidney problems: Vomiting or diarrhea can lead to dehydration, which may strain your kidneys. Look out for fatigue, swelling, or less frequent urination.
- Severe allergic reactions: Though rare, symptoms like facial swelling, trouble breathing, or a full-body rash need emergency attention.
- Low blood sugar (hypoglycemia): This reaction is more likely if you’re also on insulin or sulfonylureas for type 2 diabetes. Signs of hypoglycemia include shakiness, sweating, confusion, or fainting.
Most people will not experience these side effects, but it’s important to stay aware. If something feels wrong or you think you’re having a serious reaction, get medical care immediately.
Who shouldn’t take Rybelsus®
Rybelsus® isn’t the right fit for everyone. Certain medical conditions or risk factors may make this medication unsafe.
You shouldn’t take Rybelsus® if:
- You or a family member has a history of medullary thyroid carcinoma (MTC) or MEN 2.
- You have a known allergy to semaglutide or any of the ingredients in Rybelsus®.
- You are pregnant, planning to become pregnant, or breastfeeding, as Rybelsus® is not recommended during these times.
Your healthcare provider may advise against Rybelsus® or recommend close monitoring if you have:
- A history of pancreatitis may increase your risk of complications.
- Severe digestive problems like gastroparesis, since Rybelsus® can slow stomach emptying and make symptoms worse.
Be sure to share your complete health history with your provider before starting treatment. They can help you weigh the risks and decide if Rybelsus® is the best choice for your health goals.
For more information, visit the safety page for Rybelsus®.
Rybelsus® vs. other GLP-1s: Side effects
While all GLP-1 medications have similar core goals, the side effects you might experience can vary based on how your body responds and the specific medication you’re using. Here’s how Rybelsus® compares to other options:
| Medication | Nausea | Vomiting | Diarrhea | Constipation | Abdominal pain | Key differences |
|---|---|---|---|---|---|---|
| Rybelsus® (semaglutide – 14 mg) | 20% | 8% | 10% | 5% | 11% | Moderate digestive side effects. |
| Wegovy® (semaglutide – 2.4 mg) | 44% | 24% | 30% | 24% | 20% | Higher rates of nausea, vomiting, diarrhea, and constipation than Rybelsus®. |
| Ozempic® (semaglutide – 1 mg) | 20% | 9% | 8% | 3% | 5% | Similar nausea rates with Rybelsus® but fewer reports of abdominal pain. |
| Mounjaro/Zepbound®/ (tirzepatide – 15 mg) | 28% | 13% | 23% | 11% | 10% | More reports of diarrhea and constipation compared to Rybelsus®. |
| Saxenda® (liaglutide – 3 mg) | 39% | 16% | 20% | 19% | 5% | Higher rates of digestive side effects but fewer cases of abdominal pain. |
| Trulicity® (dualglutide – 4.5 mg) | 16% | 9% | 11% | Not reported | Not reported | Fewer nausea rates compared to Rybelsus®. |
Managing the side effects of Rybelsus®
Rybelsus® offers a convenient, pill-based option for managing type 2 diabetes—and for some, supporting weight loss—thanks to its active ingredient, semaglutide. Like other GLP-1 medications, it works by regulating appetite, slowing digestion, and improving blood sugar control. While many people experience digestive side effects at first, these often become more manageable over time, especially with dose adjustments and lifestyle changes.
As with any medication, your experience on Rybelsus® will depend on your unique health needs and how your body responds. Understanding the common side effects, potential risks, and what to expect during titration can help you stay informed and better prepared. If you’re considering Rybelsus® or already taking it, talk with your healthcare provider about how to tailor the treatment to your goals—and how to manage any bumps along the way.
If you’re looking for extra support, check if you qualify for Noom Med. You’ll be paired with a clinician who can help you explore your weight loss medication options and prescribe one if needed. Then they’ll help you create a weight loss plan, manage side effects, and stay on track with your health goals.
Note: Rybelsus®, Ozempic®, Mounjaro®, and Trulicity® are not FDA-approved for treating obesity or weight loss.
