Wegovy (Semaglutide 2.4 mg) for Weight Loss
Wegovy is a once-weekly injectable GLP-1 receptor agonist FDA-approved for chronic weight management in adults with BMI ≥30 kg/m² or BMI ≥27 kg/m² with at least one weight-related comorbidity, achieving superior weight loss (14.9-20.4%) compared to other anti-obesity medications and providing proven cardiovascular benefits. 1, 2
Key Distinction: Wegovy vs. Ozempic
Wegovy (semaglutide 2.4 mg weekly) is specifically FDA-approved for weight loss, while Ozempic (semaglutide up to 1.0 mg weekly) is approved only for type 2 diabetes management. 1, 3 The higher dose formulation in Wegovy produces substantially greater weight loss (14.9-17.4%) compared to Ozempic's 4-7% weight reduction. 1, 3
Mechanism of Action
Wegovy works through multiple pathways beyond simple appetite suppression: 4
- Hypothalamic appetite suppression through GLP-1 receptor activation in the brain 1
- Delayed gastric emptying by inhibiting gastric peristalsis and increasing pyloric tone, creating prolonged fullness 1, 4
- Glucose-dependent insulin stimulation and glucagon suppression (when blood glucose is elevated) 4
- Increased energy expenditure through metabolic effects 1
The medication has an elimination half-life of approximately 1 week, requiring 4-5 weeks to reach steady-state concentrations. 4
Weight Loss Efficacy
Real-world data demonstrates substantial and sustained weight loss: 2
- 6 months: -13.4% mean weight loss 2
- 12 months: -17.6% mean weight loss 2
- 18 months: -20.3% mean weight loss 2
- 24 months: -20.4% mean weight loss 2
At 12 months, 43.3% of patients achieved ≥20% weight loss, increasing to 50.5% at 24 months. 2 This far exceeds older weight loss medications like phentermine (3-4% weight loss) or naltrexone-bupropion (3.01% weight loss). 5, 1, 6
Cardiovascular Benefits: A Game-Changer
Wegovy is FDA-approved (2024) to reduce cardiovascular death, heart attack, and stroke in adults with obesity and established cardiovascular disease. 6
In the SELECT trial with over 17,600 participants: 6
- 20% reduction in major cardiovascular events (HR 0.80,95% CI 0.72-0.90) 1, 6
- Major cardiovascular events occurred in 6.5% with Wegovy versus 8% with placebo 6
- Benefits include improved cholesterol profiles, lower blood pressure, and decreased inflammatory markers 6
This cardiovascular protection extends beyond glycemic control and weight loss, making Wegovy particularly valuable for patients with established cardiovascular disease. 1, 6
Dosing and Titration Schedule
Slow titration is essential to minimize gastrointestinal side effects: 1, 3
- Weeks 1-4: 0.25 mg weekly 1, 3
- Weeks 5-8: 0.5 mg weekly 1, 3
- Weeks 9-12: 1.0 mg weekly 1, 3
- Weeks 13-16: 1.7 mg weekly 1, 3
- Week 17+: 2.4 mg weekly (maintenance dose) 1, 3
The medication is administered as a subcutaneous injection in the abdomen, thigh, or upper arm once weekly. 4 If significant gastrointestinal symptoms occur, extend each dose level by an additional 4 weeks before escalating. 3
Eligibility Criteria
FDA-approved indications: 1
- BMI ≥30 kg/m² (obesity) without additional requirements 1
- BMI ≥27 kg/m² with at least one weight-related comorbidity: 1
- Type 2 diabetes
- Hypertension
- Dyslipidemia
- Obstructive sleep apnea
- Cardiovascular disease
Must be used as adjunct to reduced-calorie diet and increased physical activity (minimum 150 minutes/week). 1
Absolute Contraindications
Do not prescribe Wegovy in patients with: 1, 3
- Personal or family history of medullary thyroid cancer 1, 3
- Multiple endocrine neoplasia syndrome type 2 (MEN2) 1, 3
- Pregnancy (limited data; use only if potential benefit justifies potential risk) 4
Common Side Effects and Management
Gastrointestinal effects are the most common adverse events: 1, 7
- Nausea: 17-44% of patients (typically mild-to-moderate, transient) 1
- Diarrhea: 12-32% 1
- Vomiting: 7-25% 1
- Constipation: 10-23% 1
Mitigation strategies: 1
- Slow dose titration (as outlined above)
- Reduce meal size
- Limit alcohol and carbonated beverages
- Increase fiber intake
Serious but rare risks requiring monitoring: 1, 3
- Pancreatitis (monitor for persistent severe abdominal pain) 1, 3
- Gallbladder disease (cholelithiasis, cholecystitis) 1, 3
- Acute kidney injury (monitor for dehydration during dose escalation) 1
Critical Consideration: Lifelong Treatment Required
Sudden discontinuation results in regain of one-half to two-thirds of lost weight within 1 year. 1 Weight regain is accompanied by worsening cardiometabolic risk factors, necessitating continued therapy to maintain benefits. 6 Patients must understand this is a chronic medication requiring long-term commitment. 1
Monitoring Schedule
During titration (first 16 weeks): 1
- Every 4 weeks: weight, blood pressure, gastrointestinal tolerance
After reaching maintenance dose: 1
- Every 3 months minimum: weight, blood pressure, cardiovascular risk factors, medication adherence
Treatment response evaluation: 1
- At 12-16 weeks on maximum tolerated dose
- Discontinue if <5% weight loss achieved after 3 months at therapeutic dose
Peri-Operative Considerations
Critical safety concern: Wegovy delays gastric emptying, creating aspiration risk during anesthesia. 1
- For elective surgery: Discontinue Wegovy for at least 3 weeks (three half-lives) before procedures requiring anesthesia 1
- Retained gastric contents documented even after extended fasting periods (24.2% of semaglutide users vs. 5.1% of controls) 1
- Consider gastric ultrasound pre-operatively to assess residual gastric contents 1
Special Populations
Renal impairment: No dose adjustment required across all stages of CKD, including end-stage renal disease. 4
Hepatic impairment: No dose adjustment required. 4
Elderly patients: Age alone is not a contraindication, but requires more vigilant monitoring for dehydration and blood pressure changes. 1
Type 2 diabetes: Wegovy offers dual benefits of weight loss and improved glycemic control (HbA1c reduction of approximately 1.4-1.5%). 3 However, weight loss appears lower in individuals with type 2 diabetes (4-6.2%) compared to those without diabetes (6.1-17.4%). 1
Cost Considerations
Average wholesale price is approximately $1,557-$1,600 per 30-day supply. 1 Insurance coverage varies significantly and may be a major barrier, particularly for obesity management without diabetes. 1, 7 Long-term financial planning is essential given the need for lifelong treatment. 1
Comparison to Alternatives
Wegovy vs. Tirzepatide (Mounjaro/Zepbound): 1
- Tirzepatide demonstrates superior weight loss (20.9% vs. 14.9%) 1
- Tirzepatide is a dual GIP/GLP-1 agonist with enhanced metabolic benefits 1
- However, Wegovy has proven cardiovascular outcome benefits, while tirzepatide's cardiovascular data is pending 1
- For patients with established cardiovascular disease, Wegovy may be preferred due to proven cardiovascular risk reduction 1
Wegovy vs. Phentermine: 6
- Wegovy produces 4-5 times greater weight reduction than phentermine 6
- Phentermine is FDA-approved only for short-term use (≤12 weeks) 6
- Wegovy provides cardiovascular benefits; phentermine does not 6
- Use Wegovy as first-line therapy when long-term weight management (>3 months) is needed 6
Common Pitfalls to Avoid
- Don't prescribe Wegovy without counseling about lifelong treatment necessity 1
- Don't ignore peri-operative aspiration risk – always discontinue 3 weeks before elective surgery 1
- Don't combine with other GLP-1 receptor agonists or DPP-4 inhibitors 1
- Don't forget to reduce insulin or sulfonylurea doses when adding Wegovy to diabetes regimens (increased hypoglycemia risk) 1
- Don't continue therapy if <5% weight loss after 3 months at therapeutic dose 1
Additional Metabolic Benefits
Beyond weight loss and cardiovascular protection, Wegovy demonstrates benefits in: 1, 6