Side Effects of Rybelsius (Semaglutide)
Rybelsius (oral semaglutide) commonly causes gastrointestinal side effects, including nausea, vomiting, diarrhea, and abdominal pain, which are the most frequently reported adverse events. 1
Common Side Effects
Gastrointestinal Effects
- Nausea and diarrhea: Most frequently reported gastrointestinal symptoms 1
- Vomiting (can be severe)
- Abdominal pain
- Loss of appetite
- Metallic taste
These gastrointestinal symptoms may improve if doses are taken with food or at bedtime, though the medication is recommended to be taken on an empty stomach in the morning 2.
Other Common Side Effects
- Weight loss: While this is often a desired effect, it can be significant 1
- Decreased systolic blood pressure 1
Serious Side Effects
Thyroid-Related Concerns
- Risk of thyroid tumors including cancer: In studies with rodents, semaglutide caused thyroid tumors. Patients should report any lump or swelling in the neck, hoarseness, trouble swallowing, or shortness of breath 2
Renal Effects
- Risk of worsening renal function: Dehydration due to gastrointestinal side effects may lead to acute kidney injury 2
- Potential need for dialysis in severe cases 2
Hypersensitivity Reactions
- Serious allergic reactions including:
- Swelling of face, lips, tongue, or throat
- Breathing or swallowing difficulties
- Severe rash or itching
- Fainting or dizziness
- Rapid heartbeat 2
Other Serious Concerns
- Acute gallbladder disease: Risk of cholelithiasis or cholecystitis 2
- Pulmonary aspiration during anesthesia: Delayed gastric emptying may lead to complications during surgery 2
Special Populations
Pregnancy and Breastfeeding
- Potential risk to fetus: Not recommended during pregnancy 2
- Passes into breast milk: Breastfeeding is not recommended during treatment 2
- Reproductive planning: Should be discontinued at least 2 months before planned pregnancy due to long washout period 2
Monitoring Recommendations
- Regular monitoring of renal function in patients with pre-existing kidney disease
- Monitor for signs of thyroid issues including neck swelling or voice changes
- Watch for signs of dehydration, especially in patients experiencing severe gastrointestinal symptoms
- Monitor for gallbladder disease if symptoms develop
Drug Interactions
Rybelsius may affect how other medications work, particularly:
- Oral medications taken within 30 minutes of Rybelsius 2
- Increased risk of hypoglycemia when used with insulin or sulfonylureas 2
Risk Mitigation
- Start with lower doses and titrate gradually to improve tolerability
- Take with a small sip of water (no more than 4 ounces) 2
- Wait 30 minutes before eating, drinking, or taking other oral medications 2
- Maintain adequate hydration to prevent renal complications
- Inform all healthcare providers about Rybelsius use, especially before surgical procedures
The side effect profile of Rybelsius is consistent with the GLP-1 receptor agonist drug class, with gastrointestinal effects being predominant but generally manageable with proper dosing strategies and patient education 1.