Rybelsus Side Effects

Generic name: semaglutide

Medically reviewed by Philip Thornton, DipPharm. Last updated on Nov 21, 2023.

Note: This document provides detailed information about Rybelsus Side Effects associated with semaglutide. Some dosage forms listed on this page may not apply specifically to the brand name Rybelsus.

Applies to semaglutide: subcutaneous solution.

Other dosage forms:

• oral tablet

Important warnings This medicine can cause some serious health issues

Subcutaneous route (solution)

Warning: Risk of Thyroid C-Cell Tumors. In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures.

It is unknown whether semaglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined.Semaglutide is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

Counsel patients regarding the potential risk for MTC with the use of semaglutide and inform them of symptoms of thyroid tumors (eg, a mass in the neck, dysphagia, dyspnea, persistent hoarseness).

Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with semaglutide.

Common side effects of Rybelsus

Some side effects of semaglutide may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common side effects

• diarrhea

Less common side effects

• constipation
• hair loss

Rare side effects

• bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
• change in taste
• loss of taste

Serious side effects of Rybelsus

Along with its needed effects, semaglutide (the active ingredient contained in Rybelsus) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking semaglutide:

Less common side effects

• belching
• bloated, full feeling
• excess air or gas in the stomach or intestines
• gaseous stomach pain
• heartburn
• passing gas
• recurrent fever
• stomach discomfort, fullness, or pain
• yellow eyes or skin

Rare side effects

• burning feeling in the chest or stomach
• indigestion
• stomach upset
• tenderness in the stomach area

Incidence not known

• anxiety
• blurred vision
• chest tightness
• chills
• cold sweats
• confusion
• cool, pale skin
• cough
• darkened urine
• difficulty swallowing
• discouragement
• dizziness
• fast heartbeat
• feeling sad or empty
• headache
• hives, itching
• increased heart rate
• increased hunger
• irritability
• lack of appetite
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• loss of consciousness
• loss of interest or pleasure
• nausea
• nightmares
• pains in stomach, side, or abdomen, possibly radiating to the back
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• redness of the skin
• seizures
• shakiness
• skin rash
• slurred speech
• tiredness
• trouble breathing
• trouble concentrating
• trouble sleeping
• unusual tiredness or weakness
• vomiting

For healthcare professionals

Applies to semaglutide: oral tablet, subcutaneous solution.

General adverse events

The most commonly reported adverse reactions have included nausea, vomiting, diarrhea, abdominal pain, and constipation.^[Ref]

Oncologic

GLP- 1 Receptor Agonist:

• Postmarketing reports: Medullary thyroid cancer

Cases of Medullary thyroid cancer (MTC) have been reported in patients treated with liraglutide in the postmarketing period; the data in these reports is insufficient to establish or exclude a causal relationship between MTC and GLP-1 receptor agonist use in humans.

Gastrointestinal

• Very common (10% or more): Nausea (up to 44%), increased amylase (up to 13%), increased lipase (up to 22%), diarrhea (up to 30%), vomiting (up to 24%), constipation (up to 24%), abdominal pain (up to 20%),
• Common (1% to 10%): Dyspepsia, eructation, flatulence, gastroesophageal reflux disease, abdominal distention, gastroenteritis, gastroesophageal reflux disease, gastritis, gastroenteritis (viral)
• Uncommon (0.1% to 1%): Appendicitis
• Frequency not reported: Acute and necrotizing pancreatitis, chronic pancreatitis

In clinical trials for type 2 diabetes, acute pancreatitis was confirmed by adjudication in 7 (0.3 cases per 100 patient years) and 8 patients (0.27 per 100 patient years) in 2 separate trials (compared to 3 and 10 placebo treated patients, respectively). One case of chronic pancreatitis was confirmed. In clinical trials for weight loss, 4 cases of acute pancreatitis were confirmed by adjudication (vs 1 placebo case). In weight loss trials, nausea, diarrhea, vomiting, constipation, and abdominal pain were reported more frequently than in clinical trials for type 2 diabetes.

Hypersensitivity

• Rare (less than 0.1%): Anaphylactic reaction
• Frequency not reported: Angioedema
• Postmarketing reports: Ananaphylaxis, rash, urticaria

Ocular

• Common (1% to 10%): Diabetic retinopathy complications

In a 2-year trial among patients with type 2 diabetes and high cardiovascular risk, patients treated with this drug experienced a great incidence of diabetic retinopathy complications (3% vs 1.8%). The absolute risk was greater in patients with a history of diabetic retinopathy at baseline (8.2%[drug] vs 5.2%[placebo]) than those without (0.7%[drug] vs 0.4%[placebo]).

Metabolic

• Very common (10% or more): Hypoglycemia (up to 30% when used in combination with basal insulin)
• Common (1% to 10%): Hypoglycemia, decreased appetite, weight loss

In the weight loss clinical trials, patients without type 2 diabetes experienced episodes of hypoglycemia.

Local

• Common (1% to 10%): Injection site reactions

Immunologic

• Frequency not reported: Development of anti-semaglutide (the active ingredient contained in Rybelsus) antibodies

As with other protein and peptide pharmaceuticals, patients receiving this drug have developed anti-semaglutide antibodies. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay, as well as other factor in handling of the sample. For these reasons, the incidence of antibodies cannot be directly compared with other products. Anti-drug antibodies to semaglutide have been reported in up to 1% of patients during clinical trials.

Hepatic

• Common (1% to 10%): Cholelithiasis
• Uncommon (0.1% to 1%): Cholecystitis
• Frequency not reported: Acute gallbladder disease

Cholelithiasis has been reported in 1.5% and 0.4% of patients receiving 0.5 mg and 1 mg weekly, respectively.

Other

• Very common (10% or more): Fatigue (up to 11%)

Fatigue was reported in greater than 0.4% of patients.

Nervous system

• Very common (10% or more): Headache (up to 14%)
• Common (1% to 10%): Dizziness
• Uncommon (0.1% to 1%): Dysgeusia

Renal

• Postmarketing reports: Acute kidney injury, worsening of chronic renal failure

Cardiovascular

• Common (1% to 10%): Hypotension, orthostatic hypotension
• Uncommon (0.1% to 1%): Syncope
• Frequency not reported: Increased heart rate

A mean increase in heart rate of 2 to 3 beats per minute (bpm) was reported in clinical trials for type 2 diabetes. In weight loss clinical trials, a mean increase in resting heart rate of 1 to 4 bpm was observed. Maximal changes from baseline at any visit of 10 to 19 bpm (41% vs 34% placebo) and 20 bpm (26% vs 16% placebo) were recorded. In weight loss clinical trials, Hypotension and orthostatic hypotension were more frequently seen in patients on concomitant antihypertensive therapy. Some reactions were related to gastrointestinal reactions and associated volume loss.

Dermatologic

• Common (1% to 10%): Hair loss

Frequently asked questions

• Rybelsus vs Ozempic for weight loss: Which to choose?
• What foods should I eat or avoid when taking Rybelsus?
• How much weight can you lose with Rybelsus?
• How long does it take for Rybelsus to start working?
• Can you just stop taking Rybelsus?
• Can you take Rybelsus if you are not diabetic?
• What's the easiest way to open a Rybelsus bottle?
• Can you take Rybelsus at night?
• Rybelsus Copay Card: Do I qualify? Savings explained

Further information

Rybelsus side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Note: Medication side effects may be underreported. If you are experiencing side effects that are not listed, submit a report to the FDA by following this guide.

Medical Disclaimer