Note: This document contains side effect information about semaglutide. Some dosage forms listed on this page may not apply to the brand name Rybelsus.

Applies to semaglutide: oral tablet. Other dosage forms:

• subcutaneous solution

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:

More common

• Anxiety
• bloating
• blurred vision
• chills
• cold sweats
• confusion
• constipation
• cool, pale skin
• cough
• darkened urine
• depression
• diarrhea
• difficulty swallowing
• dizziness
• fast heartbeat
• fever
• headache
• increased hunger
• indigestion
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• loss of appetite
• nausea
• nervousness
• nightmare
• pain in the stomach, side, or abdomen, possibly radiating to the back
• seizures
• skin rash
• slurred speech
• tightness in the chest
• trouble breathing
• unusual tiredness or weakness
• vomiting
• yellow eyes or skin

Other 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:

Less common

• Acid or sour stomach
• belching
• excess air or gas in stomach
• feeling pressure in the stomach
• heartburn
• passing gas
• stomach discomfort, swelling, tenderness, or upset

For Healthcare Professionals

Applies to semaglutide: oral tablet, subcutaneous solution.

General

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

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]).

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

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

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.

Common (1% to 10%): Hypotension, orthostatic hypotension

Uncommon (0.1% to 1%): Syncope

Frequency not reported: Increased heart rate

Dermatologic

Common (1% to 10%): Hair loss