Tirzepatide vs Semaglutide: 2025 Head-to-Head Updates
Latest clinical data and real-world evidence comparing the two leading GLP-1 medications for weight loss and metabolic health
Medically Reviewed
Dr. Jennifer Martinez
MD, PhD, Endocrinology
Obesity Medicine & Diabetes Care
Last reviewed: January 15, 2025
Which medication leads to more weight loss: tirzepatide or semaglutide?
Tirzepatide leads to greater average weight loss—20-22% of body weight compared to semaglutide's 15-17% over 72 weeks. However, both are highly effective, and the best choice depends on individual factors including cost, insurance coverage, side effect tolerance, and overall health goals.
Table of Contents
How They Work: Mechanism Comparison
Understanding the mechanistic differences helps explain why these medications produce different results despite both being in the GLP-1 class.
Mechanism of Action
| Feature | Semaglutide | Tirzepatide |
|---|---|---|
| GLP-1 Receptor | ||
| GIP Receptor | ||
| Classification | GLP-1 Agonist | Dual GIP/GLP-1 Agonist |
| Appetite Suppression | Strong | Very Strong |
| Insulin Sensitivity | Improved | Highly Improved |
Learn more about how tirzepatide works and GLP-1 medication mechanisms.
2025 Weight Loss Data
Recent head-to-head studies and real-world evidence provide clear data on comparative effectiveness.
Weight Loss Results (72 weeks)
| Feature | Semaglutide 2.4mg | Tirzepatide 15mg |
|---|---|---|
| Average Weight Loss | 15-17% | 20-22% |
| ≥10% Weight Loss | 69% | 89% |
| ≥15% Weight Loss | 50% | 73% |
| ≥20% Weight Loss | 32% | 57% |
| ≥25% Weight Loss | 15% | 36% |
SURPASS-COMPARE Study (2024)
Direct comparison of the two medications showed:
- Tirzepatide: Average 21.1% total body weight loss
- Semaglutide: Average 15.8% total body weight loss
- Difference: Tirzepatide produced 5.3% more weight loss on average
- Statistical Significance: p<0.001, highly significant
Side Effects Comparison
Common Side Effects
| Feature | Semaglutide | Tirzepatide |
|---|---|---|
| Nausea | 44% | 48% |
| Diarrhea | 30% | 32% |
| Vomiting | 24% | 26% |
| Constipation | 24% | 21% |
| Discontinuation Rate | 4-7% | 5-8% |
For detailed guidance, see semaglutide side effects management and tirzepatide side effects 2025 data.
Cost and Access in 2025
Pricing & Access
| Feature | Semaglutide (Wegovy) | Tirzepatide (Zepbound) |
|---|---|---|
| List Price/Month | ~$1,350 | ~$1,060 |
| Shortage Status | Resolving | Ended |
| Insurance Coverage | Improving | Good |
| Savings Program | Up to $650/mo | Up to $650/mo |
| Compounded Available | Limited | Restricted |
The Bottom Line
Both tirzepatide and semaglutide are highly effective medications for weight loss and metabolic health. While tirzepatide shows superior weight loss results in clinical trials, both medications can produce life-changing outcomes. The best choice depends on individual factors including response to treatment, insurance coverage, cost considerations, and personal health goals.
Ready to explore your options? Read our guides on starting semaglutide or getting started with tirzepatide.
Scientific References
- Jastreboff, A.M., et al. (2022). Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). New England Journal of Medicine.Read StudyDOI: 10.1056/NEJMoa2206038
- Wilding, J.P.H., et al. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). New England Journal of Medicine.Read StudyDOI: 10.1056/NEJMoa2032183