Rybelsus Prescribing Information, Explained Section by Section
The Rybelsus label carries a boxed warning for thyroid c-cell tumors, 9 other warnings and 3 drug interaction lines. It is approved for 2 uses.
- Boxed warning
- Thyroid C-cell tumors
- Approved uses
- 2
- Warnings
- 9
- First approved
- 2019
Rybelsus overview
Its half-life is about 1 week. After 7 d, half is gone, and after five half-lives (35 d), about 3% remains.
For type 2 diabetes, PIONEER 1 ran for 26 weeks. Weight loss was 3.7 kg, compared with 1.4 kg on placebo.
Monthly prices in US dollars include the list price and self-pay offers. Each comes from the maker's price page.
Sources: FDA label (DailyMed), healthsystemtracker.org, Novo Nordisk pricing, Novo Nordisk.
The Rybelsus boxed warning
Boxed warning: In rodents, this medicine caused thyroid C-cell tumors. Whether it does so in people remains unknown. You must not take this medicine if you or your family have a history of medullary thyroid cancer (MTC). It is also not for anyone with MEN 2.
The label words
“In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether RYBELSUS and OZEMPIC tablets cause thyroid C-cell”
Source: FDA DailyMed label.
Indications
When used with diet and exercise, this medicine lowers blood sugar in adults with type 2 diabetes.
The label words
“as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. • to reduce the risk of major”
Source: FDA DailyMed label.
Among adults at high risk who have type 2 diabetes, it reduces the chance of heart attack, stroke, or heart-related death.
The label words
“to reduce the risk of major adverse cardiovascular (CV) events (CV death, non-fatal myocardial infarction or non-fatal stroke) in adults with type 2 diabetes mellitus”
Source: FDA DailyMed label.
Contraindications
A personal or family history of medullary thyroid cancer (MTC), or MEN 2.
The label words
“personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)”
Source: FDA DailyMed label.
You had a serious allergic reaction before to semaglutide or any ingredient in the product.
The label words
“A prior serious hypersensitivity reaction to semaglutide or to any of the excipients in RYBELSUS or OZEMPIC tablets. Serious hypersensitivity reactions including anaphylaxis and angioedema”
Source: FDA DailyMed label.
Precautions and safety warnings
Thyroid C-cell tumors In rodents, it caused thyroid C-cell tumors, but whether it does in people is not known. This medicine must not be used by anyone with a personal or family history of medullary thyroid cancer (MTC), or with MEN 2.
The label words
“In mice and rats, semaglutide caused a dose-dependent and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure at”
Source: FDA DailyMed label.
Pancreatitis. The medicine can cause inflammation of the pancreas. If severe stomach pain does not go away, stop taking it and get medical care. The pain sometimes spreads to the back.
The label words
“Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including semaglutide tablets [see Adverse”
Source: FDA DailyMed label.
Worsening of diabetic eye disease Diabetic eye disease may worsen in people with type 2 diabetes, especially after a rapid drop in blood sugar. If you already have it, eye checks are important.
The label words
“In a pooled analysis of glycemic control trials, patients reported diabetic retinopathy related adverse reactions during the trial (4.2% with semaglutide tablets and 3.8% with”
Source: FDA DailyMed label.
Low blood sugar. Low blood sugar is more likely when this medicine is used with insulin or a sulfonylurea, such as glipizide or glimepiride.
The label words
“Patients receiving RYBELSUS or OZEMPIC tablets in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe”
Source: FDA DailyMed label.
Kidney injury due to fluid loss Fluid loss from vomiting or diarrhea may lead to kidney injury. Drink fluids and report heavy fluid loss.
The label words
“There have been postmarketing reports of acute kidney injury in some cases requiring hemodialysis, in patients treated with semaglutide. The majority of the reported events”
Source: FDA DailyMed label.
Reactions affecting the stomach and gut can be severe. Stomach and gut side effects are common and can be severe. This medicine is not recommended for people with severe gastroparesis.
The label words
“Use of semaglutide tablets has been associated with gastrointestinal adverse reactions, sometimes severe [see Adverse Reactions ( 6.1 )] . In clinical trials, severe gastrointestinal”
Source: FDA DailyMed label.
Serious allergic reactions. Reports of serious allergic reactions have included swelling of the face, lips or throat. If they happen, stop taking it and get help right away.
The label words
“Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported in patients treated with semaglutide tablets. If hypersensitivity reactions occur, discontinue use of RYBELSUS or OZEMPIC”
Source: FDA DailyMed label.
Gallbladder disease. Both gallstones and gallbladder inflammation can happen. Report any pain in your upper-right belly, fever, or yellow skin or eyes.
The label words
“Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and postmarketing. In placebo-controlled trials to improve”
Source: FDA DailyMed label.
Food reaching the lungs while receiving anesthesia or sedation. Food may stay in the stomach longer, which matters during deep sedation or anesthesia. Before a procedure, inform your care team.
The label words
“RYBELSUS and OZEMPIC tablets delay gastric emptying [see Clinical Pharmacology (12.2)]. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor”
Source: FDA DailyMed label.
Source: FDA DailyMed label.
Adverse reactions table
For each dose group, the label’s trials list the side effects reported most often beside placebo.
| Side effect | Placebo | Rybelsus 7 mg | Rybelsus 14 mg | More than placebo, 14 mg |
|---|---|---|---|---|
| Nausea | 6% | 11% | 20% | +14 points |
| Abdominal Pain | 4% | 10% | 11% | +7 points |
| Diarrhea | 4% | 9% | 10% | +6 points |
| Decreased appetite | 1% | 6% | 9% | +8 points |
| Vomiting | 3% | 6% | 8% | +5 points |
| Constipation | 2% | 6% | 5% | +3 points |
Source: Rybelsus label (DailyMed).
Drug interactions
The risk of low blood sugar goes up when you combine it with insulin, or with a sulfonylurea (such as glipizide or glimepiride). The doctor may lower the doses of those drugs.
The label words
“When initiating RYBELSUS or OZEMPIC tablets, consider reducing the dosage of concomitantly administered insulin secretagogue (such as sulfonylureas) or insulin to reduce the risk of”
Source: FDA DailyMed label.
Because this medicine slows stomach emptying, it may affect how your body absorbs other pills.
The label words
“Semaglutide cause a delay of gastric emptying and thereby has the potential to impact the absorption of other oral drugs. Levothyroxine exposure was increased 33%”
Source: FDA DailyMed label.
A study found that semaglutide tablets raised levothyroxine levels, so thyroid levels may need checking.
The label words
“Levothyroxine exposure was increased 33% (90% CI: 1.25 to 1.42) when administered with semaglutide tablets in a drug interaction study [see Clinical Pharmacology (12.3)].”
Source: FDA DailyMed label.
Pregnancy and breastfeeding
Stop taking it at least 2 months before a planned pregnancy. Pregnancy data are limited.
The label words
“Discontinue RYBELSUS or OZEMPIC tablets in women at least 2 months before a planned pregnancy due to the long washout period for semaglutide [see Use”
Source: FDA DailyMed label.
These tablets contain SNAC, which is also present in breast milk.
The label words
“However, SNAC and/or its metabolites are present in human milk. Since the activity of enzymes involved in SNAC clearance may be lower in infants compared”
Source: FDA DailyMed label.
Storage and patient advice
Keep each tablet in its original bottle at room temperature, protected from moisture.
The label words
“Store RYBELSUS and OZEMPIC tablets at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room”
Source: FDA DailyMed label.
Comparing this label with labels for other GLP-1 medicines
| Label | Boxed warning | Warnings | Interaction lines | Named beyond insulin and pills |
|---|---|---|---|---|
 Ozempic | Yes | 9 | 2 | Not listed |
 Wegovy | Yes | 10 | 3 | Levothyroxine |
| Rybelsus | Yes | 9 | 3 | Levothyroxine |
 Mounjaro | Yes | 9 | 4 | Birth control pills, Warfarin and narrow-range drugs |
 Zepbound | Yes | 9 | 4 | Birth control pills, Warfarin and narrow-range drugs |
 Foundayo | Yes | 9 | 6 | Strong CYP3A4 inhibitors, Strong CYP3A4 inducers, plus Birth control pills and Simvastatin |
 Trulicity | Yes | 9 | 3 | Warfarin and narrow-range drugs |
 Saxenda | Yes | 9 | 2 | Not listed |
 Victoza | Yes | 8 | 2 | Not listed |
| Byetta | No | 9 | 4 | Antibiotics and Birth control pills, along with Warfarin and narrow-range drugs |
The sources are Ozempic label (DailyMed), Wegovy label (DailyMed), Rybelsus label (DailyMed), Mounjaro label (DailyMed), Zepbound label (DailyMed), Foundayo label (DailyMed), Trulicity label (DailyMed), Saxenda label (DailyMed), Victoza label (DailyMed), and Byetta label (DailyMed).
Read the full Rybelsus label
The complete prescribing information is available at DailyMed, the National Library of Medicine label site.