Semaglutide Side Effects: A Comprehensive Review
Semaglutide commonly causes gastrointestinal side effects including nausea, vomiting, diarrhea, constipation, and abdominal pain, with a 38% higher risk of serious adverse events compared to placebo. 1
Common Side Effects
Gastrointestinal Effects
- Nausea and vomiting (most common)
- Diarrhea
- Constipation
- Abdominal pain
- Esophageal reflux
- Delayed gastric emptying 1
Other Common Side Effects
- Injection site reactions
- Elevated heart rate
- Hypoglycemia (particularly when combined with insulin or sulfonylureas) 1
Serious Adverse Events
Pancreatic Issues
- Increased risk of pancreatitis (causality not definitively established but requires monitoring)
- Discontinue medication if pancreatitis is suspected 1
Gallbladder Disease
Gastrointestinal Complications
Kidney Issues
- Acute kidney injury (use caution when initiating or increasing dose in patients with kidney disease) 1
Other Serious Concerns
- Potential delayed absorption of oral medications (monitor medications with narrow therapeutic index) 1
- Diabetic retinopathy complications (particularly in patients with pre-existing retinopathy) 2, 4
Contraindications
- Personal or family history of medullary thyroid carcinoma
- Multiple endocrine neoplasia syndrome type 2
- Pregnancy or breastfeeding 1, 5
Risk Mitigation Strategies
Dose Titration
- Gradual dose titration is recommended to mitigate gastrointestinal side effects
- For subcutaneous semaglutide: start with 0.25 mg once weekly for 4 weeks, then increase to 0.5 mg and eventually to 1.0 mg or 2.4 mg as tolerated 1, 5
Monitoring Recommendations
- Monitor for signs of pancreatitis (persistent severe abdominal pain)
- Monitor renal function in patients with kidney disease
- Monitor for gallbladder disease symptoms
- More frequent blood glucose monitoring during first 4 weeks of therapy
- Consider reducing doses of concurrent sulfonylureas (by 50%) or basal insulin (by 20%) to prevent hypoglycemia 5
Special Considerations
Renal Impairment
- No dose adjustment required for eGFR ≥30 mL/min/1.73m²
- Use with caution if eGFR <30 mL/min/1.73m² 5
Overdose Management
- Primarily supportive care
- Antiemetics for nausea/vomiting
- Correction of fluid and electrolyte imbalances
- Monitoring for hypoglycemia 6
Clinical Perspective
Despite these side effects, semaglutide has demonstrated significant benefits for weight loss (9.6-14.7% from baseline) and glycemic control 1. The American Gastroenterological Association suggests that semaglutide 2.4 mg may be prioritized over other approved anti-obesity medications for most patients due to its favorable benefit-risk profile 1.
When prescribing semaglutide, it's essential to counsel patients about potential side effects, especially gastrointestinal symptoms, which are often mild to moderate and transient but can significantly impact quality of life and medication adherence.