Wegovy (Semaglutide 2.4 mg) for Weight Management
Recommended Use and Indications
Wegovy (semaglutide 2.4 mg subcutaneous injection) is FDA-approved for chronic weight management in adults with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with at least one weight-related comorbidity such as hypertension, type 2 diabetes, or dyslipidemia, and should be used as an adjunct to reduced-calorie diet and increased physical activity. 1, 2, 3
Key Indications:
- Adults with BMI ≥30 kg/m² regardless of comorbidities 1, 2
- Adults with BMI ≥27 kg/m² plus at least one weight-related condition (hypertension, type 2 diabetes, dyslipidemia) 1, 3
- The AGA suggests prioritizing semaglutide 2.4 mg over other approved anti-obesity medications for most patients given its superior magnitude of benefit 1, 2
Dosing and Administration
Standard Titration Schedule:
Semaglutide 2.4 mg requires a gradual dose escalation over 16-20 weeks to minimize gastrointestinal adverse effects 1, 2:
- Week 0-4: 0.25 mg once weekly 1, 2
- Week 5-8: 0.5 mg once weekly 1, 2
- Week 9-12: 1.0 mg once weekly 2
- Week 13-16: 1.7 mg once weekly 2
- Week 17+: 2.4 mg once weekly (maintenance dose) 1, 2
Administration Details:
- Administer as subcutaneous injection once weekly at any time of day 1, 2
- Can be injected in abdomen, thigh, or upper arm with similar bioavailability 4
- No dose adjustment needed for renal or hepatic impairment 1, 5
Missed Dose Management:
- If 1 dose missed: administer as soon as possible within 5 days 2
- If 2 consecutive doses missed: use clinical judgment; may resume at same dose if previously well-tolerated 2
- If ≥3 consecutive doses missed: restart titration schedule 2
Expected Weight Loss Outcomes
Efficacy Data:
Semaglutide 2.4 mg produces mean weight loss of 14.9-17.4% over 68 weeks in individuals without diabetes, significantly outperforming placebo (2.4-5.7%) 1, 6, 7:
- 64.9% of patients achieve ≥10% total body weight loss (vs 12.3% with placebo) 1
- 46.1% achieve ≥15% total body weight loss (vs 5.4% with placebo) 1
- Weight loss continues through 104 weeks, with mean loss of -15.2% vs -2.6% with placebo 6
- Real-world data shows mean weight loss of -20.3% at 18 months and -20.4% at 24 months 7
Population-Specific Considerations:
- Weight loss is lower in patients with type 2 diabetes (mean 9.6%) compared to those without diabetes (14.9-17.4%) 1, 2, 6
- Efficacy is not significantly impacted by age, sex, race, ethnicity, or baseline BMI 4
Cardiovascular and Cardiometabolic Benefits
Semaglutide 2.4 mg reduces the composite incidence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke by 20% (HR 0.80) in patients with established cardiovascular disease and BMI ≥27 2:
- Particularly valuable for patients with obesity and established cardiovascular disease 2
- Improves blood pressure, lipid profiles, and insulin sensitivity 2
- May require adjustment of antihypertensive medications as weight decreases 2
Safety Profile and Adverse Effects
Common Adverse Effects:
Gastrointestinal adverse events are the most common, including nausea, vomiting, diarrhea, constipation, and abdominal pain, which are typically mild-to-moderate and decrease over time 1, 2, 6:
Serious Adverse Events:
Semaglutide shows a 38% higher risk of serious adverse events compared to placebo (95% CI 1.10-1.73), including pancreatitis, cholelithiasis, and cholecystitis 1, 2:
- Monitor for persistent severe abdominal pain (pancreatitis) 2
- Monitor for gallbladder disease symptoms 1, 2
- Risk of hypoglycemia increases when combined with insulin, sulfonylureas, or glinides 5
Absolute Contraindications:
Semaglutide is contraindicated in patients with personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 based on animal studies showing thyroid C-cell tumors 1, 2, 4:
- Also contraindicated during pregnancy or breastfeeding 5
- Not recommended in patients with clinically meaningful gastroparesis 5
Perioperative Considerations:
GLP-1 receptor agonists may increase risk of pulmonary aspiration under anesthesia even with extended fasting periods 2
Long-Term Use and Weight Maintenance
After cessation of semaglutide, significant weight regain occurs (11.6% of lost weight regained after 52 weeks), highlighting the need for long-term or lifelong use 2:
- Patients must be counseled that this medication requires long-term commitment 2
- Must be used in conjunction with lifestyle modifications (reduced-calorie diet and increased physical activity) 1, 2, 3
Monitoring Requirements
Essential Monitoring Parameters:
- Blood pressure (may need to reduce antihypertensive medications) 2
- Signs/symptoms of pancreatitis (persistent severe abdominal pain) 2
- Gallbladder disease symptoms 2
- Nutritional status 2
- Thyroid function 2
- Blood glucose if using with other antidiabetic medications 5
Drug Interactions
No clinically relevant drug-drug interactions have been observed with commonly co-administered medications including metformin, oral contraceptives, warfarin, digoxin, and atorvastatin 4:
- No dose adjustment required for co-administered oral medications 4
- Should not be used with other GLP-1 receptor agonists or DPP-4 inhibitors 2
- Use caution when combining with insulin or insulin secretagogues due to hypoglycemia risk 2
Comparison with Alternative Therapies
Tirzepatide demonstrates superior weight loss (20.9%) compared to semaglutide 2.4 mg (14.9%), representing a 6.5% additional weight loss at 72 weeks 2:
- Tirzepatide 15 mg is recommended as first choice for obesity management when available 2
- Semaglutide 2.4 mg is recommended as second choice if tirzepatide is unavailable or not tolerated 2
- Semaglutide has established cardiovascular outcome data, while tirzepatide cardiovascular outcome trials are ongoing 2
Cost and Access Considerations
Average wholesale price is approximately $1,600 for a 30-day supply, and insurance authorization may be challenging, particularly for obesity management without diabetes 2: