What are the indications and usage of Wegovy (semaglutide) for weight loss in adults with a body mass index (BMI) of 30 or higher, or a BMI of 27 or higher with at least one weight-related condition?

Wegovy (Semaglutide 2.4 mg) Indications for Weight Loss

Wegovy 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, and must be used as an adjunct to a reduced-calorie diet and increased physical activity. 1, 2

FDA-Approved Patient Eligibility Criteria

Primary Indication

• Adults with BMI ≥30 kg/m² (obesity) qualify for treatment without additional requirements 1, 3
• Adults with BMI ≥27 kg/m² (overweight) qualify if they have at least one weight-related comorbid condition, including: 1, 3
  • Type 2 diabetes mellitus
  • Hypertension
  • Dyslipidemia
  • Obstructive sleep apnea
  • Cardiovascular disease

Asian Population Considerations

• For Asian populations, obesity is defined as BMI ≥25 kg/m² based on WHO recommendations, as this population experiences increased health risks at lower BMI thresholds 4
• Semaglutide 2.4 mg demonstrated significant efficacy in Asian populations with BMI ≥25 kg/m², achieving -16.0% mean weight loss at 44 weeks versus -3.1% with placebo 4

Mechanism of Action

Semaglutide is a GLP-1 receptor agonist that reduces body weight through multiple mechanisms: 2

• Stimulates glucose-dependent insulin secretion and lowers glucagon secretion 2
• Delays gastric emptying, reducing the rate at which nutrients enter circulation postprandially 2
• Suppresses appetite through actions on the hypothalamus 3, 5
• Increases satiety and reduces food intake 3, 5

Expected Weight Loss Outcomes

Clinical Trial Data

• Mean weight loss of 14.9-17.4% at 68 weeks in adults with obesity without diabetes 3, 5, 6
• 96% of patients achieve ≥5% weight loss, 78% achieve ≥10% weight loss, and 53% achieve ≥15% weight loss at 44 weeks 4
• Real-world data shows mean weight loss of -13.4% at 6 months, -17.6% at 12 months, -20.3% at 18 months, and -20.4% at 24 months 6

Weight Loss in Special Populations

• Patients with type 2 diabetes experience lower weight loss (4-6.2%) compared to those without diabetes (6.1-17.4%) 3, 5
• Weight loss appears to be dose-dependent and requires long-term use for sustained benefit 3, 5

Cardiovascular Benefits Beyond Weight Loss

Semaglutide 2.4 mg provides significant cardiovascular risk reduction, particularly in patients with established cardiovascular disease: 3, 7

• 20% reduction in composite cardiovascular death, nonfatal MI, or nonfatal stroke (HR 0.80,95% CI 0.72-0.90) in the SELECT trial 3
• Cardiovascular benefits are independent of baseline adiposity and weight loss, with only 33% of benefit mediated through waist circumference reduction 7
• Cardioprotective effects persist across all baseline weight and waist circumference categories 7

Absolute Contraindications

Do not prescribe Wegovy in patients with: 1, 3

• Personal or family history of medullary thyroid cancer
• Multiple endocrine neoplasia syndrome type 2 (MEN2)
• Pregnancy or active attempts to conceive
• Hypersensitivity to semaglutide or any product components

Required Lifestyle Interventions

Pharmacotherapy must be combined with: 1, 3

• Reduced-calorie diet with 500-kcal deficit below daily requirements
• Minimum 150 minutes per week of physical activity
• Resistance training to preserve lean body mass and prevent muscle loss
• Behavioral counseling and lifestyle modification support

Treatment Duration and Long-Term Use

Wegovy requires indefinite, lifelong treatment for sustained weight loss: 3, 8

• Discontinuation results in 50-67% weight regain within one year 8
• Treatment must be maintained continuously to preserve weight loss benefits 3, 8
• Early responders (≥5% weight loss after 3 months) should continue long-term therapy 1, 8
• If weight loss is <5% after 3 months at therapeutic dose, consider discontinuation and alternative approaches 1, 8

Administration and Dosing

Semaglutide 2.4 mg is administered as once-weekly subcutaneous injection with the following titration schedule: 3, 8

• Weeks 1-4: 0.25 mg weekly
• Weeks 5-8: 0.5 mg weekly
• Weeks 9-12: 1.0 mg weekly
• Weeks 13-16: 1.7 mg weekly
• Week 17 onward: 2.4 mg weekly (maintenance dose)

Gradual dose escalation is essential to minimize gastrointestinal side effects 3, 8

Common Pitfalls to Avoid

• Do not prescribe for short-term weight loss goals - patients must understand this is lifelong therapy 3, 8
• Do not skip the titration schedule - rapid dose escalation significantly increases gastrointestinal adverse effects 3, 8
• Do not prescribe without concurrent lifestyle interventions - medication alone is insufficient 1, 3
• Do not ignore cardiovascular disease status - patients with established CVD derive additional cardiovascular benefits beyond weight loss 3, 7