What is the comparison of GLP-1 (Glucagon-like peptide-1) receptor agonists, such as liraglutide (Victoza), semaglutide (Ozempic), and dulaglutide (Trulicity), for weight loss?

Comparison of GLP-1 Receptor Agonists for Weight Loss

Semaglutide 2.4mg weekly provides significantly greater weight loss compared to liraglutide 3.0mg daily and other GLP-1 receptor agonists, with semaglutide achieving approximately 15-16% total body weight loss versus 5-8% with liraglutide. 1

Efficacy Comparison

Weight Loss Results

• Semaglutide 2.4mg weekly:

  • 15.8% mean weight loss at 68 weeks 1
  • 14.9-16.0% mean weight loss in clinical trials 2
  • Most effective for weight reduction (-12.47 kg) 3

• Liraglutide 3.0mg daily:

  • 6.4% mean weight loss at 68 weeks when compared directly to semaglutide 1
  • 8.4 kg mean weight loss (approximately 8%) in phase III trials 4
  • Second most effective (-5.24 kg) 3

• Other GLP-1 RAs:

  • Semaglutide 1.0mg: -3.74 kg 3
  • Liraglutide 1.8mg: -3.29 kg 3
  • Exenatide: Modest changes ranging from +0.3 to 2.96 kg 5

Achievement of Clinically Significant Weight Loss

When comparing semaglutide 2.4mg vs liraglutide 3.0mg directly:

• ≥10% weight loss: 70.9% vs 25.6% of participants (odds ratio 6.3) 1
• ≥15% weight loss: 55.6% vs 12.0% of participants (odds ratio 7.9) 1
• ≥20% weight loss: 38.5% vs 6.0% of participants (odds ratio 8.2) 1

Mechanisms of Action

Both medications work through similar mechanisms but with different potencies:

• Delayed gastric emptying: Liraglutide delays gastric emptying of solids (median 70 min at 5 weeks), which correlates with weight loss outcomes 6
• Reduced food intake: Both reduce maximum tolerated volume of food 6
• Metabolic effects: Both improve glycemic parameters, with semaglutide showing greater HbA1c reduction 3

Safety Profile

Adverse Events

• Gastrointestinal side effects: Most common for both medications

  • Semaglutide: 84.1% reported GI adverse events 1
  • Liraglutide: 82.7% reported GI adverse events 1
  • Nausea with liraglutide: 40% vs 14.8% with placebo 5
  • Vomiting with liraglutide: 16% vs 4.3% with placebo 5

• Treatment discontinuation:

  • Semaglutide: 13.5% discontinued treatment 1
  • Liraglutide: 27.6% discontinued treatment 1

• Serious adverse events:

  • Liraglutide 3.0mg has higher incidence of serious adverse events than semaglutide 2.4mg 3
  • No significant difference in serious adverse events between liraglutide and placebo (RR 1.22) 5

Clinical Considerations

Dosing and Administration

• Semaglutide: Once-weekly subcutaneous injection with gradual titration over 16-17 weeks to reach 2.4mg 2
• Liraglutide: Once-daily subcutaneous injection with titration over 4-5 weeks to reach 3.0mg 2, 4

Special Populations

• Type 2 diabetes: Both agents improve glycemic control

  • Liraglutide reduced HbA1c by 0.5-0.93% compared to placebo 5
  • Semaglutide showed greater HbA1c reduction (-1.48%) than liraglutide (-1.23%) 3

• NAFLD/NASH: GLP-1 RAs reduce hepatic fat and steatosis

  • Liraglutide showed more frequent resolution of NASH (9/23 vs 2/22) and less progression of fibrosis (2/23 vs 8/22) compared to placebo 5

Practical Considerations

• Adherence: Weekly dosing with semaglutide may improve adherence compared to daily liraglutide 5
• Lean body mass: Liraglutide without lifestyle intervention may result in more lean body mass loss than with lifestyle co-interventions 5
• Cost: Both medications are expensive, with costs ranging from $1,300-1,600 for a 30-day supply 2

Recommendations for Clinical Practice

1. For maximum weight loss: Choose semaglutide 2.4mg weekly as first-line GLP-1 RA therapy when weight loss is the primary goal 1

2. For patients with GI intolerance: Consider liraglutide which may be better tolerated by some patients despite higher discontinuation rates overall 1

3. For patients with type 2 diabetes: Both agents are effective, but semaglutide provides greater weight loss and HbA1c reduction 3

4. Optimize outcomes:

   • Combine with lifestyle modifications including physical activity to preserve lean body mass 5
   • Follow recommended titration schedules to minimize side effects 2
   • Monitor for gastrointestinal symptoms and adjust titration speed accordingly 2

5. Monitor for adverse effects:

   • Gastrointestinal symptoms (nausea, vomiting, diarrhea)
   • Gallbladder disorders
   • Hypoglycemia (more common with semaglutide) 3