GLP-1 Receptor Agonists for Weight Loss
Semaglutide (Wegovy) is the most effective GLP-1 receptor agonist for weight loss, achieving up to 15% weight reduction compared to 8% with liraglutide (Saxenda). 1, 2
Recommended GLP-1 Medications for Weight Loss
First-Line Option
- Semaglutide (Wegovy) - 2.4 mg subcutaneous injection once weekly
- Most effective GLP-1 option with mean weight loss of 14.9% at 68 weeks 2
- FDA approved for obesity treatment in 2021 2
- Demonstrated cardiovascular benefits in the SELECT study (HR 0.80; 95% CI 0.72-0.90) 2, 1
- Requires gradual dose titration: start at 0.25 mg weekly for 4 weeks, then 0.5 mg, 1.0 mg, and 1.7 mg weekly every 4 weeks until reaching maintenance dose of 2.4 mg 2
Alternative Option
- Liraglutide (Saxenda) - 3.0 mg subcutaneous injection daily
- Achieves mean weight loss of 8.0% at 56 weeks 2
- FDA approved for obesity treatment in 2014 2
- May be preferred for some patients due to cost and availability 2
- Requires gradual dose titration: start with 0.6 mg daily for 7 days, followed by doses of 1.2 mg, 1.8 mg, and 2.4 mg daily every 7 days until reaching maintenance dose of 3.0 mg 2
Indications for Use
- BMI ≥30, or BMI ≥27 with weight-related comorbidities such as:
- Type 2 diabetes
- Hypertension
- Obstructive sleep apnea 2
Mechanism of Action
GLP-1 receptor agonists promote weight loss through multiple mechanisms:
- Suppression of appetite via action on hypothalamus
- Increased satiety
- Delayed gastric emptying
- Increased glucose-dependent insulin release
- Decreased glucagon secretion 1, 2
Comparative Efficacy
A systematic review and meta-analysis found that:
- Semaglutide 2.4 mg achieved the greatest weight loss (-12.47 kg)
- Followed by liraglutide 3.0 mg (-5.24 kg)
- Semaglutide 1.0 mg (-3.74 kg)
- Liraglutide 1.8 mg (-3.29 kg) 3
Adverse Effects Management
Common adverse effects include:
Gastrointestinal symptoms (most common)
- Nausea (40% with liraglutide vs 14.8% with placebo)
- Vomiting (16% with liraglutide vs 4.3% with placebo)
- Diarrhea
- Dyspepsia 2
Management of adverse effects:
- Start at low dose and titrate slowly
- Reduce meal size
- Avoid high-fat diet, alcohol, and carbonated drinks
- Avoid in patients with gastroparesis 2
Important Clinical Considerations
- Long-term use is necessary - significant weight regain occurs after discontinuation (11.6% of lost weight regained after stopping semaglutide) 2
- Combine with lifestyle modifications for optimal results 2
- Monitor for rare but serious adverse events:
- Pancreatitis (<0.1%)
- Symptomatic gallstones (<0.05%)
- Cardiac arrhythmia/tachycardia 2
- Medication interactions: May delay absorption of oral medications requiring rapid onset of action 2
- Contraindications: Should not be used with other GLP-1 receptor agonists or dipeptidyl peptidase-4 inhibitors 2
Emerging Options
- Tirzepatide (dual GLP-1/GIP receptor agonist) shows even greater efficacy with weight loss of up to 20.9% at 72 weeks 2, 1
- FDA approved for obesity treatment in November 2023 2
Clinical Pearls
- Patients may achieve strong response at submaximal doses and could continue at that dose long-term 2
- If more than 2 consecutive doses are missed, clinical judgment is required for subsequent dosing 2
- Semaglutide has a half-life of approximately 1 week, reaching steady state in 4-5 weeks 4, 5
GLP-1 receptor agonists represent a significant advancement in pharmacotherapy for obesity, with semaglutide demonstrating the most impressive weight loss results and cardiovascular benefits among currently available options.