What are the potential complications associated with Wegovy (semaglutide)?

Potential Complications of Wegovy (Semaglutide)

Wegovy (semaglutide) is associated with several significant complications including gastrointestinal side effects, risk of thyroid C-cell tumors, pancreatitis, gallbladder disease, diabetic retinopathy complications, and acute kidney injury. 1

Common Complications

Gastrointestinal Side Effects

• Most common adverse effects (typically mild-to-moderate and transient):
  • Nausea and vomiting
  • Diarrhea
  • Constipation
  • Abdominal pain
  • Dyspepsia

These GI effects are typically most pronounced during dose escalation and tend to diminish over time. In clinical trials, approximately 4.5% of patients discontinued treatment due to GI side effects compared to 0.8% in placebo groups. 2

Serious Complications

Thyroid C-cell Tumors

• Black box warning: Risk of thyroid C-cell tumors, including medullary thyroid carcinoma (MTC)
• Contraindicated in patients with:
  • Personal or family history of MTC
  • Multiple endocrine neoplasia syndrome type 2 (MEN 2)
• Patients should be counseled about symptoms of thyroid tumors:
  • Neck mass
  • Dysphagia
  • Dyspnea
  • Persistent hoarseness 1

Pancreatitis

• Acute pancreatitis reported in clinical trials (0.3 cases per 100 patient-years)
• Monitor for signs and symptoms:
  • Persistent severe abdominal pain (may radiate to back)
  • With or without vomiting
• If pancreatitis is confirmed, Wegovy should not be restarted 1

Gallbladder Disease

• Increased risk of cholelithiasis and cholecystitis
• In placebo-controlled trials, cholelithiasis was reported in 1.5% of patients treated with lower doses and 0.4% with higher doses 1, 3

Diabetic Retinopathy Complications

• Increased risk in patients with pre-existing diabetic retinopathy
• Rapid improvement in glucose control may temporarily worsen retinopathy
• Higher absolute risk increase in patients with history of diabetic retinopathy (8.2% vs 5.2%) compared to those without (0.7% vs 0.4%) 1

Acute Kidney Injury

• Post-marketing reports of acute kidney injury and worsening of chronic renal failure
• May require hemodialysis in some cases
• More common in patients experiencing severe GI side effects leading to dehydration
• Monitor renal function when initiating or escalating doses, especially in patients with severe GI reactions 1

Other Notable Complications

Hypersensitivity Reactions

• Serious reactions including anaphylaxis and angioedema have been reported
• Discontinue use if hypersensitivity reactions occur 1

Hypoglycemia

• Increased risk when used with insulin secretagogues or insulin
• May require dose reduction of these medications 1

Cardiovascular Effects

• Increased heart rate (2-3 beats per minute above baseline) 1

Laboratory Abnormalities

• Increases in amylase (13%) and lipase (22%) 1

Special Population Considerations

Pregnancy

• Contraindicated during pregnancy
• Women of reproductive potential must use effective contraception
• Potential risks to the fetus based on animal studies 1, 4

Breastfeeding

• Not recommended during breastfeeding 4

Monitoring Recommendations

1. Regular monitoring of patients for GI side effects and signs of dehydration
2. Renal function assessment when initiating or escalating doses, particularly in patients with severe GI reactions
3. Retinopathy screening in patients with diabetes, especially those with pre-existing retinopathy
4. Pregnancy testing in women of reproductive potential
5. Monitor for gallbladder disease symptoms 1, 4

Risk Mitigation Strategies

1. Gradual dose escalation following recommended schedule to minimize GI side effects
2. Adequate hydration to prevent dehydration-related complications
3. Dose adjustment of concomitant medications (insulin, sulfonylureas) to prevent hypoglycemia
4. Patient education regarding warning signs of serious complications
5. Regular follow-up to assess for adverse effects 4

Despite these potential complications, Wegovy has demonstrated significant benefits for weight loss and cardiovascular risk reduction, with a 20% reduction in cardiovascular death in the SELECT trial for patients with obesity or overweight and cardiovascular disease. 5