Side effects
Rybelsus side effects
Rybelsus side effects are mostly digestive: in the label's pooled placebo-controlled trials, nausea affected 11% of people on 7 mg and 20% on 14 mg, against 6% on placebo.1 The label also carries a boxed warning about thyroid C-cell tumors seen in mice and rats, and lists rare serious risks such as pancreatitis.1
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Most common side effects
The label's main frequency table pools two placebo-controlled trials and lists every reaction reported by at least 5% of patients on the tablets:1
| Side effect | 7 mg | 14 mg | Placebo |
|---|---|---|---|
| Nausea1 | 11% | 20% | 6% |
| Stomach (abdominal) pain1 | 10% | 11% | 4% |
| Diarrhea1 | 9% | 10% | 4% |
| Decreased appetite1 | 6% | 9% | 1% |
| Vomiting1 | 6% | 8% | 3% |
| Constipation1 | 6% | 5% | 2% |
Stomach or gut effects of any kind were reported by 32% on 7 mg and 41% on 14 mg, against 21% on placebo.1 Severe cases: 0.6% on 7 mg, 2.0% on 14 mg and 0.3% on placebo.1 They led 4% on 7 mg and 8% on 14 mg to stop treatment, against 1% on placebo.1 Most nausea, vomiting and diarrhea happened while the dose was being stepped up, which is why the label raises it in stages.1
Other digestive and lab findings
| Finding | 7 mg | 14 mg | Placebo |
|---|---|---|---|
| Bloating (abdominal distension)1 | 2% | 3% | 1% |
| Indigestion (dyspepsia)1 | 3% | 0.6% | 0.6% |
| Burping (eructation)1 | 0.6% | 2% | 0% |
| Gas (flatulence)1 | 2% | 1% | 0% |
| Acid reflux (GERD)1 | 2% | 2% | 0.3% |
| Gastritis1 | 2% | 2% | 0.8% |
- Heart rate: an average rise of 1 to 3 beats per minute on 7 mg and 14 mg, with no change on placebo.1
- Pancreatic enzymes in blood tests: amylase rose 10% on 7 mg and 13% on 14 mg on average, and lipase 30% and 34%; neither rise was seen on placebo.1
- Antibodies: 14 of 2,924 people (0.5%) on semaglutide tablets in trials of 26 to 78 weeks developed anti-semaglutide antibodies, and 7 (0.2%) had antibodies that also reacted with natural GLP-1.1
- Stopping over the long term: in the 4-year cardiovascular trial, 15.5% on 14 mg stopped the study drug because of any adverse event, against 11.6% on placebo.1
Serious but less common
- Pancreatitis: reported as a serious adverse event in 6 of 4,116 people on semaglutide tablets across 9 trials (0.1 events per 100 patient-years), against 1 person on comparator treatments.1 Fatal and non-fatal hemorrhagic or necrotizing pancreatitis has occurred with GLP-1 drugs, semaglutide tablets included.1 The warning sign is severe stomach pain that will not go away, sometimes reaching the back, and the label says to stop Rybelsus if pancreatitis is suspected.1
- Low blood sugar: with Rybelsus alone for 26 weeks, severe episodes (needing another person's help) occurred in 1% on 7 mg and 0% on 14 mg, against 0% on placebo.1 The risk rises with insulin or a sulfonylurea: added to insulin for 52 weeks, blood sugar fell below 54 mg/dL in 26% on 7 mg and 30% on 14 mg, against 32% on placebo plus insulin.1 Signs include shakiness, sweating, dizziness, confusion, a fast heartbeat and hunger.1 Glucose results by trial: Rybelsus and blood sugar.
- Diabetic eye disease: in a 2-year trial of semaglutide injection, retinopathy complications occurred in 3% vs 1.8% on placebo, and in 8.2% vs 5.2% among people who already had retinopathy.1 The label asks patients to report vision changes.1
- Gallbladder disease: gallstones in 1% on 7 mg in the glucose trials. In the 4-year cardiovascular trial, gallstones affected 1.1% vs 0.9% on placebo and gallbladder inflammation (cholecystitis) 1.1% vs 0.7%.1 Symptoms include upper stomach pain, fever, yellow skin or eyes and clay-colored stools.1
- Kidney injury: acute kidney injury, in some cases needing dialysis, has been reported after approval, mostly in people dehydrated by nausea, vomiting or diarrhea.1 The Medication Guide asks patients to drink fluids and report those symptoms if they do not go away.1
- Serious allergic reactions: anaphylaxis and angioedema have been reported.1 The label says to stop Rybelsus and get help right away for swelling of the face, lips, tongue or throat, trouble breathing or swallowing, severe rash, fainting or a very fast heartbeat.1
- NAION: in June 2025 the European Medicines Agency's safety committee judged this eye condition a very rare side effect of semaglutide, affecting up to 1 in 10,000 users.2 It advises anyone with sudden vision loss or rapidly worsening eyesight to contact a doctor without delay, and says semaglutide should be stopped if NAION is confirmed.2 The US label does not list NAION.1
Reported after approval
These come from voluntary reports received after approval, so their frequency cannot be reliably estimated and a link to the drug is not always established: acute and necrotizing pancreatitis (sometimes fatal), ileus, intestinal obstruction, severe constipation including fecal impaction, anaphylaxis, angioedema, rash, hives, gallbladder inflammation (cholecystitis), gallstones needing gallbladder removal, dizziness, altered skin sensation (dysesthesia), taste changes (dysgeusia), headache, pulmonary aspiration during anesthesia or deep sedation, acute kidney injury and hair loss (alopecia).1
Warnings
- Boxed warning: in mice and rats, semaglutide caused thyroid C-cell tumors that increased with dose and treatment length, at exposures relevant to people. Whether Rybelsus causes these tumors, including medullary thyroid carcinoma (MTC), in humans is unknown.1 Symptoms to report are a lump in the neck, trouble swallowing, shortness of breath or lasting hoarseness.1 The label calls routine calcitonin tests or thyroid ultrasound of uncertain value for catching MTC early.1
- Who must not take it: anyone with a personal or family history of MTC, anyone with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), and anyone who had a serious allergic reaction to semaglutide or a tablet ingredient.1
- Severe gastroparesis (very slow stomach emptying): Rybelsus is not recommended.1
- Surgery and sedation: Rybelsus slows stomach emptying, and rare cases of food or liquid entering the lungs during anesthesia or deep sedation have been reported with GLP-1 drugs.1 The label says to tell every provider about Rybelsus before a planned procedure.1
- Other pills: slower stomach emptying can change how other oral medicines are absorbed.1 Levothyroxine exposure rose 33% when taken with semaglutide tablets, and the label advises extra monitoring for drugs with a narrow therapeutic range.1
- Pregnancy and breastfeeding: human data are too limited to judge the risk, and animal studies showed harm to the fetus.1 The label says to stop at least 2 months before a planned pregnancy.1 Breastfeeding is not recommended, because SNAC from the tablet passes into breast milk and may build up in infants.1
- Children: safety and effectiveness are not established under 18.1
- Overdose: the label advises calling Poison Help or going to an emergency room.1 With a half-life of about 1 week, observation and treatment may need to last a long time.1
Related pages
Read the full Rybelsus profile, the label schedule in Rybelsus dosage and the trial results in Rybelsus benefits and uses. Side effects across the drug class are covered in GLP-1 side effects, and the weekly injection's list is in Ozempic side effects.
More on Rybelsus
Rybelsus dosage
Published dosing information for Rybelsus from labels and studies, with its source, and why it is not advice for you.
Rybelsus benefits and uses
What published sources report about Rybelsus and its uses, with the evidence level of each finding. No promises.
Frequently asked questions
Does Rybelsus cause appetite loss?
It can. In the label's pool of two placebo-controlled trials, decreased appetite was reported by 6% of people on 7 mg and 9% on 14 mg, against 1% on placebo.1 It is one of the six most common reactions on the label, along with nausea, stomach pain, diarrhea, vomiting and constipation.1 The label treats it as a side effect: Rybelsus is not approved for weight loss.1
Do Rybelsus side effects go away?
The label reports that most nausea, vomiting and diarrhea happened while the dose was being stepped up, and its Medication Guide says these effects are most common when people first start the tablets.1 The gradual schedule exists to reduce them.1 The label gives no time by which they stop. It tells patients to drink fluids and to report nausea, vomiting or diarrhea that does not go away, because dehydration has been linked to kidney injury, in some cases needing dialysis.1
Can Rybelsus cause suicidal thoughts?
FDA reviewed this for the whole GLP-1 class. A meta-analysis of 91 placebo-controlled trials with 107,910 patients found no increased risk of suicidal thoughts or behavior, and in January 2026 FDA asked makers to remove that warning from the Saxenda, Wegovy and Zepbound labels.3 FDA noted that labels of GLP-1 drugs approved for type 2 diabetes, which include Rybelsus, did not include that warning.3 FDA still advises anyone with new or worsening depression, suicidal thoughts or unusual changes in mood or behavior to tell a health care professional.3
Can Rybelsus affect your eyes?
Two eye issues are on record. In the glucose-lowering trials, diabetic retinopathy reactions occurred in 4.2% on semaglutide tablets vs 3.8% on comparator treatments, and the label warns that a rapid improvement in blood sugar can temporarily worsen retinopathy.1 Separately, the EU medicines agency's safety committee concluded in June 2025 that NAION, an eye condition that can affect vision, is a very rare side effect of semaglutide medicines including Rybelsus, affecting up to 1 in 10,000 users.2 The US label does not list NAION.1
Written by D2C Peptides Editorial Team.
Pending qualified review.
Updated .
Sources
- RYBELSUS and OZEMPIC (semaglutide) tablets, Prescribing Information and Medication Guide (NDA 213051/S-030, revised 1/2026). U.S. Food and Drug Administration (Novo Nordisk labeling), 2026.
- PRAC concludes eye condition NAION is a very rare side effect of semaglutide medicines Ozempic, Rybelsus and Wegovy. European Medicines Agency (news, 6 June 2025), 2025.
- FDA Requests Removal of Suicidal Behavior and Ideation Warning from Glucagon-Like Peptide-1 Receptor Agonist (GLP-1 RA) Medications (Drug Safety Communication, 01-13-2026). U.S. Food and Drug Administration, 2026.