Efficacy of Wegovy (Semaglutide) Tablets for Weight Loss
Critical Clarification: Wegovy is Injectable, Not a Tablet
Wegovy (semaglutide 2.4 mg) is administered as a once-weekly subcutaneous injection, not as tablets. There is no tablet formulation of Wegovy approved for weight loss 1. Oral semaglutide (Rybelsus) exists only for type 2 diabetes management and is significantly less potent for weight management than injectable formulations 1.
Weight Loss Efficacy of Injectable Wegovy
Injectable semaglutide 2.4 mg weekly produces a mean weight loss of 14.9% at 68 weeks, representing the most effective FDA-approved obesity medication prior to tirzepatide. 1, 2
Magnitude of Weight Loss
- At 6 months: Mean weight loss of 13.4% of baseline body weight 3
- At 12 months: Mean weight loss increases to 17.6% 4, 3
- At 18 months: Mean weight loss reaches 20.3% 3
- At 24 months: Weight loss plateaus at approximately 20.4% 3
Proportion Achieving Clinically Meaningful Weight Loss
- ≥5% weight loss: 86.4% of patients at 68 weeks (vs. 31.5% with placebo) 2
- ≥10% weight loss: 69.1% of patients (vs. 12.0% with placebo) 2
- ≥15% weight loss: 50.5% of patients (vs. 4.9% with placebo) 2
- ≥20% weight loss: 13.1% at 6 months, increasing to 50.5% at 24 months 3
Absolute Weight Reduction
- Mean absolute weight loss of 15.3 kg (33.7 lbs) compared to 2.6 kg (5.7 lbs) with placebo at 68 weeks 2
- Treatment difference of 12.7 kg (28 lbs) versus placebo 2
Cardiometabolic Benefits Beyond Weight Loss
Semaglutide provides substantial cardiovascular risk reduction independent of weight loss alone. 1
- Cardiovascular events: 20% reduction in composite cardiovascular death, nonfatal MI, or nonfatal stroke (HR 0.80) in patients with established cardiovascular disease and BMI ≥27 1, 4
- Blood pressure: Clinically meaningful reductions in systolic and diastolic blood pressure 1
- Lipid profile: Improvements in triglycerides and LDL cholesterol 1
- Inflammatory markers: Reduction in C-reactive protein levels 1
Eligibility Criteria
Adults qualify for Wegovy when:
- BMI ≥30 kg/m² (obesity) without additional requirements 1
- BMI ≥27 kg/m² with at least one weight-related comorbidity (hypertension, dyslipidemia, type 2 diabetes, obstructive sleep apnea, cardiovascular disease) 1
Administration and Dosing
Wegovy requires slow titration over 16 weeks to minimize gastrointestinal adverse 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)
Subcutaneous injection sites: Abdomen, thigh, or upper arm, administered once weekly on the same day 1
Time to Maximal Benefit
Patients must remain on the maximum tolerated dose (2.4 mg weekly) for at least 12 months to achieve full therapeutic response. 4 Weight loss continues to increase from 13.4% at 6 months to 17.6% at 12 months, demonstrating that semaglutide does not show maximal benefit until after 6 months of therapy 4, 3.
Safety Profile
Common Adverse Events
- Gastrointestinal effects are the most frequent: nausea (typically transient and mild-to-moderate), diarrhea, vomiting, and constipation 1, 2, 5
- These symptoms usually subside within 4-8 weeks as the dose is titrated 1
- Treatment discontinuation due to gastrointestinal events occurs in 4.5% of patients (vs. 0.8% with placebo) 2
Serious Adverse Events
- Pancreatitis: Increased risk (38% higher than placebo); discontinue immediately if persistent severe abdominal pain develops 1
- Gallbladder disease: Increased risk of cholelithiasis and cholecystitis 1, 4
Absolute Contraindications
- Personal or family history of medullary thyroid carcinoma 1, 2
- Multiple endocrine neoplasia syndrome type 2 (MEN 2) 1, 2
Mandatory Lifestyle Modifications
Wegovy must be combined with:
- Dietary intervention: 500-kcal daily deficit below maintenance requirements 1, 4
- Physical activity: Minimum 150 minutes per week of moderate-intensity exercise 1, 4
- Resistance training: To preserve lean body mass during weight loss 4
Treatment Duration and Weight Maintenance
Semaglutide requires lifelong use to maintain weight loss. 1, 4 Significant weight regain (11.6% of lost weight) occurs within 52 weeks after discontinuation, highlighting the chronic nature of obesity pharmacotherapy 1.
Comparison to Alternative Agents
Tirzepatide 15 mg weekly demonstrates superior weight loss (20.9% at 72 weeks) compared to semaglutide 2.4 mg (14.9% at 68 weeks). 1, 4 However, semaglutide remains the preferred choice for patients with established cardiovascular disease due to proven cardiovascular outcome benefits 1, 4.
Treatment Response Evaluation
Discontinue therapy if weight loss is <5% after 3 months at therapeutic dose (2.4 mg weekly), as early non-responders are unlikely to benefit from continued treatment. 1, 4
Cost Considerations
- Average wholesale price: approximately $1,619 per 30-day supply 1
- Insurance authorization may be challenging, particularly for obesity management without diabetes 1
Common Pitfalls to Avoid
- Do not initiate at the maintenance dose (2.4 mg): Rapid titration markedly increases gastrointestinal adverse events and discontinuation rates 1
- Do not evaluate efficacy before 12 months: Maximal weight loss requires at least 6-12 months of therapy at the maintenance dose 4, 3
- Do not prescribe without lifestyle intervention: All clinical trials incorporated a 500-kcal deficit and 150 minutes of weekly physical activity 4
- Do not assume tablets exist: Wegovy is only available as a subcutaneous injection 1