Comparative Weight Loss Efficacy of Mounjaro vs. Wegovy at Different Doses
Tirzepatide (Mounjaro) demonstrates superior weight loss efficacy compared to semaglutide (Wegovy) across all doses, with the 15 mg weekly dose of tirzepatide producing approximately 5-7% more weight loss than the maximum 2.4 mg weekly dose of semaglutide. 1
Direct Comparison of Weight Loss Efficacy by Dose
Tirzepatide (Mounjaro)
- 5 mg weekly: 15.0% mean weight loss at 72 weeks 2
- 10 mg weekly: 19.5% mean weight loss at 72 weeks 2
- 15 mg weekly: 20.9% mean weight loss at 72 weeks 2
Semaglutide (Wegovy)
- 2.4 mg weekly: 14.9-16.0% mean weight loss at 68 weeks 2, 3
- 1.7 mg weekly: Similar but slightly less efficacy than 2.4 mg dose 1
- 1.0 mg weekly: Less efficacious than higher doses for weight loss 4
Head-to-Head Comparison Data
The most recent and highest quality evidence from the SURMOUNT-5 trial (2025) directly comparing these medications showed:
- Tirzepatide produced a mean weight loss of 20.2% compared to 13.7% with semaglutide at 72 weeks (difference of 6.5%) 1
- Waist circumference reduction was significantly greater with tirzepatide (-18.4 cm vs. -13.0 cm) 1
- More participants achieved significant weight loss milestones with tirzepatide:
- ≥10% weight loss: More common with tirzepatide
- ≥15% weight loss: More common with tirzepatide
- ≥20% weight loss: More common with tirzepatide
- ≥25% weight loss: More common with tirzepatide 1
A 2025 meta-analysis confirmed tirzepatide's superior efficacy:
- Overall mean difference: 4.23% more weight loss with tirzepatide vs. semaglutide 5
- Higher doses of tirzepatide (>10 mg) showed even greater advantage: 6.50% more weight loss 5
- Longer treatment duration (>6 months) increased the difference: 5.00% more weight loss 5
Dose-Response Relationship
Both medications demonstrate a clear dose-response relationship:
- Tirzepatide: Weight loss increases substantially from 5 mg (15.0%) to 10 mg (19.5%) to 15 mg (20.9%) 2
- Semaglutide: Weight loss increases with dose escalation, but the effect is less pronounced than with tirzepatide 3
Mechanism of Action Differences
The superior efficacy of tirzepatide may be explained by its dual-hormone agonist mechanism:
- Tirzepatide acts as both a GLP-1 receptor agonist AND a glucose-dependent insulinotropic polypeptide (GIP) receptor agonist 2, 6
- Semaglutide acts solely as a GLP-1 receptor agonist 2
This dual mechanism appears to provide additive effects on appetite suppression, gastric emptying, and metabolic regulation 6.
Safety and Tolerability Comparison
Both medications have similar safety profiles:
- Most common adverse events are gastrointestinal (nausea, vomiting, diarrhea)
- Side effects are typically mild to moderate and occur primarily during dose escalation
- No significant differences in serious adverse events between the two medications 1
Clinical Implications
When choosing between these medications for weight management:
- For maximum weight loss potential, tirzepatide 15 mg weekly offers the greatest efficacy 2, 5, 1
- For patients who cannot tolerate higher doses, even lower doses of tirzepatide (5-10 mg) may provide similar or greater weight loss than maximum-dose semaglutide 2, 5
- Both medications require long-term use to maintain weight loss benefits, as significant weight regain occurs after discontinuation 2
Caveats and Considerations
- Individual response may vary based on genetic factors, baseline weight, and adherence to lifestyle modifications
- Cost and insurance coverage often influence medication selection in real-world practice
- Both medications should be used in conjunction with lifestyle modifications (diet and exercise) for optimal results 2, 3
- Cardiovascular benefits have been demonstrated with both medications, which may influence selection for patients with or at risk for cardiovascular disease 2