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

Tirzepatide vs. Semaglutide for Weight Loss

Tirzepatide (Mounjaro) is superior to semaglutide (Wegovy) for weight loss, demonstrating significantly greater weight reduction of approximately 20.9% vs. 14.9-16.0% at maximum doses over similar treatment durations. 1

Comparative Efficacy

Weight Loss Results

• Tirzepatide demonstrates dose-dependent weight loss:

  • 5 mg weekly: 15.0% at 72 weeks
  • 10 mg weekly: 19.5% at 72 weeks
  • 15 mg weekly: 20.9% at 72 weeks 1

• Semaglutide weight loss:

  • 2.4 mg weekly: 14.9-16.0% at 68 weeks 1

• Meta-analysis confirms tirzepatide's superiority with a mean difference of 4.23% greater weight loss compared to semaglutide (95% CI: 3.22-5.25; P<0.01) 2

Mechanism of Action

• Tirzepatide: Dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist 3, 1
• Semaglutide: Single GLP-1 receptor agonist 3, 4

Glycemic Control

• Tirzepatide provides superior glycemic control with HbA1c reductions up to 2.30% at 15 mg dose
• Semaglutide shows HbA1c reductions of 1.86% 1, 5

Dosing Considerations

Optimal Dosing

• Tirzepatide: Target dose of 15 mg weekly for maximum weight loss 1
• Semaglutide: Target dose of 2.4 mg weekly for maximum weight loss 1

Dose-Response Relationship

• Higher tirzepatide doses (>10 mg) show greater superiority over semaglutide (mean difference 6.50%, 95% CI: 5.93-7.08) compared to lower doses (≤10 mg) (mean difference 3.89%, 95% CI: 2.12-5.65) 2

Safety Profile

Common Adverse Events

• Both medications have similar safety profiles with primarily gastrointestinal side effects:
  • Nausea (17-22% for tirzepatide, 18% for semaglutide)
  • Diarrhea (13-16% for tirzepatide, 12% for semaglutide)
  • Vomiting (6-10% for tirzepatide, 8% for semaglutide) 5

Hypoglycemia Risk

• Low risk with both medications:
  • Tirzepatide: 0.2-1.7% depending on dose
  • Semaglutide: 0.4% 5

Cost-Effectiveness

• Tirzepatide provides better value for money than semaglutide for weight reduction
• Cost needed to treat per 1% of body weight reduction:
  • Tirzepatide: $985 (95% CI: $908-$1075)
  • Semaglutide: $1845 (95% CI: $1707-$1989) 6

Clinical Recommendations

1. For patients seeking maximum weight loss, tirzepatide at 15 mg weekly is the preferred option due to its superior efficacy 1, 2

2. Treatment should be continued indefinitely in responders to prevent significant weight regain 1

3. Assess weight loss response at 3 months:

   • If <5% weight loss is achieved, consider adjusting dose or switching medications 1

4. Both medications should be combined with lifestyle modifications:

   • 500-kcal daily deficit diet
   • 150 minutes of physical activity per week 1

Caveats and Considerations

• Both medications require gradual dose titration to minimize gastrointestinal side effects 1, 5
• The American Diabetes Association acknowledges tirzepatide's superior weight loss efficacy compared to semaglutide 1
• Duration of treatment effect is an important consideration - NICE recommends semaglutide for a maximum treatment duration of 2 years 1
• Patients with type 1 diabetes may also benefit from these medications (off-label), with tirzepatide showing greater weight loss (21.4%) compared to semaglutide (9.1%) 7