Wegovy (Semaglutide 2.4 mg) for Weight Loss
Wegovy (semaglutide 2.4 mg weekly) is the recommended GLP-1 receptor agonist for chronic weight management in adults with BMI ≥30 kg/m² or BMI ≥27 kg/m² with weight-related comorbidities, producing 14.9-15.8% weight loss at 68 weeks when combined with lifestyle modifications. 1, 2
FDA-Approved Indications and Eligibility
- Wegovy is FDA-approved exclusively for patients with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with at least one weight-related comorbidity such as hypertension, dyslipidemia, type 2 diabetes, or obstructive sleep apnea. 1, 3
- The medication must be used as an adjunct to reduced-calorie diet (500-kcal daily deficit) and increased physical activity (150 minutes weekly), not as monotherapy. 1, 4
- Wegovy should NOT be used in normal weight individuals for fitness or aesthetic purposes, as it lacks FDA approval and safety data in this population and causes lean body mass loss. 3
Dosing and Titration Schedule
Start at 0.25 mg weekly and escalate gradually over 16 weeks to minimize gastrointestinal side effects: 1
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)
If 2 consecutive doses are missed, resume at the same dose if previously tolerated; if 3+ doses are missed, restart the titration schedule. 1
Weight Loss Efficacy
Wegovy produces superior weight loss compared to other anti-obesity medications: 1, 2, 5
- Mean weight loss of 14.9-15.8% at 68 weeks versus 2.4% with placebo 1, 6, 2
- 86.4% of patients achieve ≥5% weight loss, 69.1% achieve ≥10%, and 50.5% achieve ≥15% weight loss 2
- Sustained weight loss of -15.2% maintained at 104 weeks (2 years) 7, 5
- Weight loss is lower in patients with type 2 diabetes (4-6.2%) compared to those without diabetes (6.1-17.4%) 1, 4
Comparison to Other GLP-1 Agonists
- Wegovy (semaglutide 2.4 mg) produces significantly greater weight loss than Saxenda (liraglutide 3.0 mg): -15.8% versus -6.4% at 68 weeks (difference of -9.4 percentage points) 6
- Tirzepatide (Zepbound) demonstrates superior efficacy with 20.9% weight loss, representing a 6% absolute advantage over semaglutide 1
Cardiovascular Benefits
Wegovy reduces major adverse cardiovascular events in patients with established cardiovascular disease and obesity: 1
- 20% reduction in composite cardiovascular death, nonfatal MI, or nonfatal stroke (HR 0.80,95% CI 0.72-0.90) in the SELECT trial 1
- The SUSTAIN-6 trial showed 26% reduction in cardiovascular outcomes (HR 0.74,95% CI 0.58-0.95) 1
- Prioritize Wegovy over tirzepatide in patients with established cardiovascular disease due to proven cardiovascular outcome benefits 1
Safety Profile and Adverse Effects
Common Side Effects
Gastrointestinal adverse events are the most frequent, occurring in 82-84% of patients: 1, 4
- Nausea (most common), vomiting, diarrhea, constipation, and abdominal pain 1, 4
- These effects are typically mild-to-moderate, transient, and subside with time 2, 5
- Gradual dose titration significantly reduces gastrointestinal symptoms 1, 4
- Treatment discontinuation due to GI events occurs in 4.5% of patients 2
Serious Adverse Events
Pooled data shows 38% higher risk of serious adverse events compared to placebo (95% CI 1.10-1.73): 1, 4
- Increased risk of pancreatitis and gallbladder disease (cholelithiasis, cholecystitis) 1, 4
- Monitor for persistent severe abdominal pain suggesting pancreatitis 1
- Perioperative aspiration risk: Retained gastric contents documented even after extended fasting periods, requiring medication discontinuation 10-14 days before elective surgery 1
Absolute Contraindications
Wegovy is contraindicated in patients with: 1, 3, 4
- Personal or family history of medullary thyroid cancer
- Multiple endocrine neoplasia syndrome type 2 (MEN2)
Drug Interactions
- Do not combine with other GLP-1 receptor agonists or DPP-4 inhibitors 1
- Use caution with insulin or insulin secretagogues due to hypoglycemia risk 1
Long-Term Use and Weight Maintenance
Wegovy requires lifelong use to maintain weight loss: 1, 4
- Significant weight regain occurs after discontinuation: 11.6% of lost weight regained within 52 weeks of stopping 1, 4
- Patients must be counseled that this is a chronic disease requiring long-term pharmacotherapy 1
- Evaluate efficacy at 12-16 weeks on maximum tolerated dose; if inadequate response, consider treatment intensification with metabolic surgery or additional agents 1
Monitoring Requirements
Assess patients at least every 3 months for: 1
- Weight loss progress and medication adherence
- Gastrointestinal adverse effects, particularly during dose escalation 4
- Blood pressure (may require antihypertensive adjustment as weight decreases) 1
- Signs of pancreatitis or gallbladder disease 1
- Nutritional status to prevent protein and micronutrient deficiency 3
- Body composition assessment if concerned about lean mass loss 3
Special Populations
Type 2 Diabetes
- Wegovy provides dual benefits of glycemic control and weight loss in patients with type 2 diabetes 1, 4
- Mean HbA1c reduction of 1.48% compared to placebo 1
- Weight loss is consistently lower in diabetic patients (4-6.2%) versus non-diabetic patients (6.1-17.4%) 1, 4
Cardiovascular Disease
- Prioritize Wegovy in patients with both obesity and established cardiovascular disease due to proven 20% reduction in cardiovascular events 1
Practical Implementation
Combine Wegovy with comprehensive lifestyle modifications: 1, 4
- Reduced-calorie diet with 500-kcal daily deficit 4
- 150 minutes of physical activity per week 4
- Resistance training to preserve lean body mass and prevent muscle loss 1, 3
- Behavioral interventions for sustainable weight management 1
Dietary Modifications to Reduce GI Side Effects
- Reduce meal size and eat slowly 1
- Limit alcohol and carbonated beverages 1
- Avoid high-fat, greasy foods during dose escalation 1