What are the risks and benefits of Wegovy (semaglutide)?

Benefits and Risks of Wegovy (Semaglutide)

Wegovy (semaglutide) offers significant weight reduction benefits but comes with important gastrointestinal side effects and potential serious adverse events including gallbladder disease, pancreatitis, and retinopathy complications.

Benefits of Wegovy

• Significant weight reduction: Clinical trials demonstrate that semaglutide 2.4 mg weekly leads to approximately 15% weight loss from baseline compared to only 2.4% with placebo, with most patients achieving at least 5% weight reduction 1
• Cardiovascular benefits: Semaglutide reduces the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) by 26% in patients with type 2 diabetes and established cardiovascular disease 2
• Improved cardiometabolic risk factors: Treatment leads to improvements in cholesterol profiles, blood pressure, and inflammatory markers 3
• Renal benefits: May provide approximately 20% reduction in risk of composite renal outcomes, primarily through reduction in macroalbuminuria 2
• Improved physical functioning: Patients report increased physical functioning compared to placebo 1

Risks and Side Effects

Common Side Effects

• Gastrointestinal effects: Nausea, vomiting, diarrhea, constipation, and abdominal pain are the most frequent adverse effects, typically dose-dependent and more pronounced during initial treatment or dose escalation 3, 4
• Fatigue, altered taste (dysgeusia), and dizziness 5
• Injection site reactions 3

Serious Adverse Events

• 38% higher risk of serious adverse events compared to placebo 3
• Gallbladder disease: Increased risk of cholelithiasis (gallstones) and cholecystitis 3, 5
• Pancreatitis: Acute pancreatitis was confirmed in clinical trials at a rate of 0.3 cases per 100 patient-years 5
• Diabetic retinopathy complications: Higher risk, particularly in patients with pre-existing retinopathy 3, 5
• Increased heart rate: Mean increase of 2-3 beats per minute 5
• Thyroid C-cell tumors: Risk based on animal studies, with unknown relevance to humans 5

Absolute Contraindications

• Personal or family history of medullary thyroid carcinoma (MTC) 5
• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 5
• Known hypersensitivity to semaglutide or product components 5
• Pregnancy or breastfeeding 5, 3

Relative Contraindications and Precautions

• History of pancreatitis: Wegovy has not been studied in patients with a history of pancreatitis 5
• Severe gastroparesis: May experience worsened symptoms due to delayed gastric emptying 3
• Prior gastric surgery: Use with caution 3
• Diabetic retinopathy: Monitor closely for progression 3, 5
• Concomitant use with insulin or insulin secretagogues: Increased risk of hypoglycemia 3, 5

Practical Management Considerations

Dosing and Administration

• Start with 0.25 mg weekly for 4 weeks (initiation dose, not effective for weight control) 5
• Increase to 0.5 mg weekly for at least 4 weeks 5
• May increase to 1 mg weekly if additional glycemic control needed 5
• Maximum recommended dose is 1 mg weekly for diabetes (Ozempic) and 2.4 mg weekly for weight management (Wegovy) 5, 1

Monitoring Recommendations

• Regular monitoring of renal function, especially in those with pre-existing kidney disease 3
• Monitor for signs of pancreatitis (persistent severe abdominal pain, sometimes radiating to the back, with or without vomiting) 5
• Eye examination prior to initiation in patients with diabetes, particularly those with existing retinopathy 3
• Monitor for gallbladder disease 3

Managing Side Effects

• Gradual dose titration to minimize gastrointestinal side effects 3
• Reduce meal size to manage nausea and vomiting 3
• Limit alcohol and carbonated drinks to reduce reflux symptoms 3
• Avoid high-fat diets to help with constipation 3

Special Populations

• Renal impairment: Can be used with caution in severe renal impairment, with careful monitoring 3
• Pregnancy: Potential risks to the fetus based on animal studies; should only be used if potential benefit justifies potential risk 5
• Patients on oral hormonal contraceptives: Consider switching to non-oral method or adding barrier method for 4 weeks after initiation and after each dose escalation 3