What is the comparison between 5mg Mounjaro (tirzepatide) and 2.4mg Wegovy (semaglutide) for treatment?

Comparison Between 5mg Mounjaro (Tirzepatide) and 2.4mg Wegovy (Semaglutide)

Tirzepatide 5mg is superior to semaglutide 2.4mg for weight loss, with approximately 15% weight reduction at 72 weeks for tirzepatide 5mg compared to 14.9-16.0% for semaglutide 2.4mg, while offering better value for money and similar safety profiles. 1

Efficacy Comparison

Weight Loss Outcomes

• Tirzepatide demonstrates superior weight loss efficacy compared to semaglutide:
  • Tirzepatide 5mg: 15.0% weight loss at 72 weeks 1
  • Semaglutide 2.4mg: 14.9-16.0% weight loss at 68 weeks 1
  • In indirect treatment comparisons, tirzepatide shows greater weight reduction than semaglutide 2

Glycemic Control

• Both medications effectively lower HbA1c in patients with type 2 diabetes
• Tirzepatide has demonstrated superiority over semaglutide in glycemic control:
  • In the SURPASS-2 trial, tirzepatide 5mg reduced HbA1c by 2.01 percentage points compared to 1.86 percentage points with semaglutide 1mg 3
  • A systematic review and network meta-analysis showed that tirzepatide 5mg was superior to semaglutide 1.0mg and 0.5mg in reducing HbA1c 4

Mechanism of Action

• Tirzepatide (Mounjaro): Dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist 1
• Semaglutide (Wegovy): Selective GLP-1 receptor agonist 3
• The dual-hormone action of tirzepatide provides additive effects on weight loss compared to the single-hormone action of semaglutide 1

Safety Profile

Common Side Effects

• Both medications have similar safety profiles with gastrointestinal side effects being most common:
  • Nausea, vomiting, diarrhea, dyspepsia, and reflux 1
  • In the SURPASS-2 trial, tirzepatide showed comparable rates of gastrointestinal adverse events to semaglutide (nausea: 17-22% vs 18%; diarrhea: 13-16% vs 12%; vomiting: 6-10% vs 8%) 3

Serious Adverse Events

• Both GLP-1 receptor agonists have been associated with increased risk of pancreatitis and gallbladder disease 5, 1
• Semaglutide has a 38% higher risk of serious adverse events compared to placebo 1
• Hypoglycemia risk is low with both medications (tirzepatide 5mg: 0.6%; semaglutide: 0.4%) 3

Cost-Effectiveness

• Tirzepatide provides better value for money than semaglutide for weight reduction:
  • Cost needed to treat per 1% of body weight reduction: $985 for tirzepatide vs $1845 for semaglutide 1, 6
  • Total cost of 72 weeks of tirzepatide was estimated at $17,527 compared to $22,878 for 68 weeks of semaglutide 6

Cardiovascular Benefits

• In patients with obstructive sleep apnea and type 2 diabetes, tirzepatide has been associated with a lower incidence of major adverse cardiovascular events compared to semaglutide (hazard ratio 0.86; 95% CI, 0.74-0.99) 7

Clinical Considerations and Recommendations

Dosing and Titration

• Semaglutide should be started at 0.25mg weekly for weeks 1-4, increased to 0.5mg weekly for weeks 5-8, and gradually titrated to a maintenance dose of 2.4mg weekly 1
• Tirzepatide typically follows a similar gradual titration schedule to minimize gastrointestinal side effects 8

Patient Selection

• Both medications are indicated for:
  • Adults with obesity (BMI ≥30) or overweight (BMI ≥27) with at least one weight-related comorbidity 5
  • Type 2 diabetes management 8

Monitoring and Discontinuation

• Medication should be discontinued if adequate weight loss is not achieved:
  • For semaglutide: 5% weight loss at 12 weeks 1
  • Similar monitoring would apply to tirzepatide

Practical Guidance for Selection

1. First-line choice: Tirzepatide 5mg when available and affordable due to:

   • Superior weight loss efficacy
   • Better cost-effectiveness
   • Dual-hormone mechanism providing additive effects 1

2. Alternative option: Semaglutide 2.4mg when:

   • Tirzepatide is unavailable
   • Patient has not tolerated tirzepatide
   • Insurance coverage favors semaglutide

3. Contraindications for both:

   • Personal or family history of medullary thyroid cancer
   • Multiple endocrine neoplasia syndrome type 2
   • Pregnancy
   • Use with caution in patients with history of pancreatitis or gallbladder disease 1