What is the comparison between Wegovy (semaglutide) and Mounjaro (tirzepatide) for weight loss?

Tirzepatide Provides Superior Weight Loss Compared to Semaglutide for Obesity Management

Tirzepatide (Mounjaro) is more effective than semaglutide (Wegovy) for weight loss, producing approximately 5-7% greater weight reduction at maximum doses. 1

Comparative Efficacy

Weight Loss Outcomes

• Tirzepatide (Mounjaro):

  • 15 mg weekly: 20.9% weight loss at 72 weeks 2
  • 10 mg weekly: 19.5% weight loss at 72 weeks 2
  • 5 mg weekly: 15.0% weight loss at 72 weeks 2

• Semaglutide (Wegovy):

  • 2.4 mg weekly: 14.9-16.0% weight loss at 68 weeks 3, 2

• Direct comparison:

  • Meta-analysis shows tirzepatide produces significantly greater weight loss than semaglutide (mean difference = 4.23%; 95% CI: 3.22-5.25; P < 0.01) 1
  • Higher doses of tirzepatide (>10 mg) show even greater superiority (mean difference = 6.50%; 95% CI: 5.93-7.08; P < 0.01) 1

Dose-Response Relationship

• Both medications demonstrate dose-dependent weight loss effects 2
• Tirzepatide shows a stronger dose-response relationship with significantly better outcomes at higher doses 1
• Duration of treatment also impacts results, with longer treatment periods (>6 months) showing greater differences between the medications 1

Mechanism of Action

• Tirzepatide: Dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist 3
• Semaglutide: GLP-1 receptor agonist only 3, 2
• The dual receptor action of tirzepatide likely explains its superior efficacy for weight loss 3, 1

Safety and Adverse Effects

Both medications share similar safety profiles:

• Common adverse effects:

  • Gastrointestinal symptoms (nausea, vomiting, diarrhea, constipation) 3, 2
  • Most side effects are transient, mild-to-moderate in severity 2
  • Side effects typically occur during dose escalation 2

• Serious adverse events:

  • Semaglutide shows 38% higher risk of serious adverse events vs. placebo 3
  • Both medications require monitoring for pancreatitis and gallbladder disease 3, 2
  • Both contraindicated in patients with personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 3, 2

Long-term Considerations

• Weight regain:

  • Significant weight regain occurs after discontinuation of either medication 4
  • With semaglutide discontinuation, 11.6% of lost weight is regained within 52 weeks 2, 4
  • Long-term use is necessary to maintain weight loss benefits 2, 4

• Cardiovascular benefits:

  • Semaglutide reduces risk of cardiovascular events in adults with overweight/obesity 3
  • In the SELECT trial, semaglutide reduced composite incidence of cardiovascular death, nonfatal MI, or nonfatal stroke (HR 0.80; 95% CI, 0.72-0.90) 3
  • Both medications offer cardiometabolic benefits beyond weight loss 2

Clinical Application

• Patient selection:

  • Both medications are indicated for adults with BMI ≥30 kg/m² or ≥27 kg/m² with weight-related comorbidities 3
  • Patients with type 2 diabetes typically experience less weight loss than those without diabetes 3, 2
  • Off-label use in type 1 diabetes shows promising results (9.1% weight loss with semaglutide vs. 21.4% with tirzepatide) 5

• Practical considerations:

  • Both medications require gradual dose titration to minimize side effects 2
  • Both should be combined with lifestyle modifications (reduced-calorie diet and physical activity) 3, 2
  • Both are administered as weekly subcutaneous injections at maintenance dose 3, 2

Pitfalls and Caveats

• Weight regain after discontinuation:

  • Plan for long-term therapy as significant weight regain occurs after stopping either medication 2, 4
  • In the STEP 4 trial, participants who switched from semaglutide to placebo regained 6.9% of lost weight 4

• Therapeutic inertia:

  • For patients not reaching goals, treatment should be intensified rather than maintained at ineffective doses 3

• Contraindications:

  • Both medications contraindicated in pregnancy 3
  • Use with caution in patients with history of pancreatitis or gallbladder disease 3
  • Neither medication has been extensively studied in nursing mothers 3

In conclusion, while both medications are effective for weight management, the evidence clearly demonstrates that tirzepatide provides superior weight loss outcomes compared to semaglutide, with a similar safety profile. For patients seeking maximum weight reduction, tirzepatide would be the preferred option.