What is the comparison between Liraglutide (Glucagon-like peptide-1 (GLP-1) receptor agonist) and Semaglutide (GLP-1 receptor agonist) for weight loss?

Semaglutide vs Liraglutide for Weight Loss

Semaglutide is significantly more effective than liraglutide for weight loss, achieving approximately 15-17% weight reduction compared to 5-6% with liraglutide. 1, 2

Comparative Efficacy

Weight Loss Outcomes

• Semaglutide 2.4mg weekly:

  • Mean weight loss: 14.9-17.4% at 68 weeks 1
  • 64.9% of patients achieve ≥10% weight loss 1
  • 46.1% of patients achieve ≥15% weight loss 1

• Liraglutide 3.0mg daily:

  • Mean weight loss: 5-6% 1
  • Approximately 33% of patients achieve ≥10% weight loss 1
  • In direct comparison, liraglutide achieved only 6.4% weight loss vs 15.8% with semaglutide 2

Head-to-Head Comparison

In the STEP 8 randomized clinical trial, semaglutide demonstrated clear superiority:

• 9.4 percentage points greater weight loss than liraglutide (15.8% vs 6.4%) 2
• Significantly higher odds of achieving clinically meaningful weight loss thresholds:
  • ≥10% weight loss: 70.9% vs 25.6% (OR 6.3) 2
  • ≥15% weight loss: 55.6% vs 12.0% (OR 7.9) 2
  • ≥20% weight loss: 38.5% vs 6.0% (OR 8.2) 2

Administration and Convenience

Semaglutide

• Once-weekly subcutaneous injection 1
• 16-week dose escalation schedule:
  • Weeks 1-4: 0.25mg weekly
  • Weeks 5-8: 0.5mg weekly
  • Weeks 9-12: 1.0mg weekly
  • Weeks 13-16: 1.7mg weekly
  • Week 17+: 2.4mg weekly (maintenance) 1

Liraglutide

• Once-daily subcutaneous injection 1
• 4-week titration schedule to reach maintenance dose 1
• More frequent injections may affect adherence

Safety and Adverse Effects

Common Side Effects

Both medications share similar adverse effect profiles, primarily gastrointestinal:

• Nausea (40% with liraglutide) 3
• Vomiting (16% with liraglutide) 3
• Diarrhea and constipation 1

Comparative Safety

• In the STEP 8 trial, treatment discontinuation rates were:
  • Semaglutide: 13.5%
  • Liraglutide: 27.6% 2
• Gastrointestinal adverse events were reported at similar rates:
  • Semaglutide: 84.1%
  • Liraglutide: 82.7% 2

Serious Adverse Events

• Liraglutide: No significant difference in serious adverse events compared to placebo (RR 1.22; 95% CI 1.00-1.50) 3
• Rare but reported events with both medications include:
  • Pancreatitis (<0.1% with liraglutide) 3
  • Gallbladder disease (<0.05% with liraglutide requiring hospitalization) 3
  • Suicidal ideation (rare reports with semaglutide) 1

Metabolic Benefits

Both medications provide metabolic benefits beyond weight loss:

• Improved glycemic control
• Reduced cardiovascular risk factors 1

In patients with type 2 diabetes:

• Liraglutide showed modest HbA1c reduction (MD -0.5 to -0.93%) 3
• Semaglutide demonstrates superior glycemic control compared to liraglutide 1, 4

Clinical Decision-Making

When to Choose Semaglutide

• When maximum weight loss is the primary goal
• In patients who prefer weekly over daily injections
• For patients who can tolerate the longer dose escalation period

When to Consider Liraglutide

• When weekly injections are not feasible
• If insurance coverage favors liraglutide
• When faster dose titration is needed (4 weeks vs 16 weeks)

Practical Considerations

• Cost and access: Both medications are expensive; insurance coverage varies
• Injection burden: Weekly (semaglutide) vs daily (liraglutide) administration
• Titration period: Longer with semaglutide (16 weeks) vs liraglutide (4 weeks)
• Contraindications for both: Personal/family history of medullary thyroid carcinoma, multiple endocrine neoplasia type 2, pregnancy 1

Conclusion

For patients seeking weight loss, semaglutide 2.4mg weekly offers substantially greater efficacy than liraglutide 3.0mg daily, with a similar safety profile and the convenience of once-weekly administration. The choice between these medications should primarily be based on desired magnitude of weight loss, with semaglutide being the clear leader in efficacy.