GLP-1 Receptor Agonists Approved for Weight Loss Only
Liraglutide 3.0 mg (Saxenda) and semaglutide 2.4 mg (Wegovy) are the GLP-1 receptor agonists FDA-approved specifically for weight loss only, while tirzepatide (Zepbound) is a dual GIP/GLP-1 receptor agonist also approved for weight management. 1
FDA-Approved Medications for Weight Loss Indication
Liraglutide 3.0 mg (Saxenda)
- FDA approved in 2014 specifically for weight management in adults with BMI ≥30 or BMI ≥27 with at least one weight-related comorbidity 1
- Administered as once-daily subcutaneous injection 2
- Achieves mean weight loss of 5.24-6.1% at 6 months and approximately 4-6% over longer periods 2, 1
- Should be discontinued if patient has not lost at least 4% of body weight after 16 weeks of treatment 1
Semaglutide 2.4 mg (Wegovy)
- FDA approved in June 2021 for chronic weight management, not for diabetes treatment 2, 1, 3
- Administered as once-weekly subcutaneous injection 2, 4
- Demonstrates superior weight loss of 14.9-17.4% in non-diabetic patients with obesity at 68 weeks 2, 1
- Real-world data shows mean weight loss of -14.6 kg (-14.1%) after 1 year of treatment 5
- Most patients (83.5%) reach the maximum dose of 2.4 mg during treatment 5
Tirzepatide (Zepbound)
- FDA approved in November 2023 for weight management as a dual GIP/GLP-1 receptor agonist 2, 1
- Administered as once-weekly subcutaneous injection 2
- Achieves superior weight loss of 20.9% at 72 weeks, the highest among all approved agents 2
- Real-world data demonstrates mean weight loss of -17.2 kg (-16.5%) after 1 year 5
- Only 25.9% of patients reach the maximum dose of 15 mg in real-world practice 5
Critical Distinction: Weight Loss vs. Diabetes Formulations
Semaglutide Formulations
- Wegovy (2.4 mg weekly): FDA-approved exclusively for weight management 2, 1
- Ozempic (up to 1.0 mg weekly): FDA-approved only for type 2 diabetes, NOT for weight loss 2
- Rybelsus (oral): FDA-approved only for type 2 diabetes, NOT for weight management 2, 6
Tirzepatide Formulations
Eligibility Criteria for Weight Loss Indication
All three medications share identical FDA-approved eligibility criteria 1:
- BMI ≥30 kg/m² (obesity), OR
- BMI ≥27 kg/m² with at least one weight-related comorbidity (hypertension, type 2 diabetes, obstructive sleep apnea, cardiovascular disease)
Comparative Efficacy for Weight Loss Only
Tirzepatide demonstrates the greatest weight loss (20.9%), followed by semaglutide 2.4 mg (14.9%), and liraglutide showing the least (5.24-6.1%) 2, 1
- Tirzepatide produces 6% absolute advantage over semaglutide 2.4 mg (20.9% vs 14.9% weight loss) 2
- Semaglutide 2.4 mg significantly outperforms liraglutide (14.9% vs 6.0% weight loss) 2
- Weight loss appears greater in non-diabetic patients (6.1-17.4%) compared to those with diabetes (4-6.2%) 2
Shared Safety Profile and Contraindications
All three agents are absolutely contraindicated in patients with personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 2, 1
Common Adverse Effects
- Gastrointestinal effects predominate: nausea (17-40%), vomiting (6-16%), diarrhea (12-16%), constipation 2, 1
- Serious but rare risks include pancreatitis and gallbladder disease (cholelithiasis, cholecystitis) 2, 1
- Semaglutide shows 38% higher rate of serious adverse events compared to placebo (95% CI 1.10-1.73) 2
Clinical Considerations
Long-Term Use Required
- Significant weight regain occurs after cessation: 11.6% of lost weight regained after 52 weeks of stopping semaglutide 2
- Lifelong use may be necessary for sustained weight loss 2, 1
Must Be Combined with Lifestyle Modifications
- All agents must be used as adjuncts to reduced-calorie eating pattern and increased physical activity 2, 1
- Resistance training should be incorporated to preserve lean body mass 2