Both semaglutide (brand names Wegovy and Ozempic) and tirzepatide (brand names Mounjaro and Zepbound) are revolutionary medications for weight loss. But they work differently, produce different results, and come with different trade-offs.
This comprehensive comparison breaks down everything you need to know to choose between these two medications.
Quick Comparison
| Feature | Semaglutide | Tirzepatide |
|---|---|---|
| Brand Names | Wegovy, Ozempic | Mounjaro, Zepbound |
| Mechanism | GLP-1 agonist only | Dual GIP/GLP-1 agonist |
| Average Weight Loss | 15-20% body weight | 20-25% body weight |
| FDA Approval | 2021 (Wegovy) | 2023 (Zepbound) |
| Injection Frequency | Once weekly | Once weekly |
| Side Effect Severity | Moderate | Slightly higher |
| Brand Name Cost | $1,000-1,400/month | $1,000-1,400/month |
| Compounded Cost | $150-400/month | $200-500/month |
How They Work: The Key Difference
Semaglutide: Single-Action GLP-1
Semaglutide is a GLP-1 receptor agonist. It mimics only one natural hormone (GLP-1) that your intestines produce after eating. This hormone:
- Signals your brain to reduce appetite
- Slows gastric emptying by ~50%
- Improves insulin secretion when blood sugar is elevated
Tirzepatide: Dual-Action GIP/GLP-1
Tirzepatide is a dual GIP/GLP-1 receptor agonist. It mimics TWO hormones simultaneously:
- GLP-1 effects: All the same mechanisms as semaglutide
- GIP effects: Additional appetite reduction, improved fat metabolism, enhanced insulin sensitivity
- Slows gastric emptying by ~70% (more than semaglutide)
This dual mechanism is why tirzepatide typically produces 25-30% more weight loss than semaglutide.
Weight Loss Results: Clinical Trial Data
1Semaglutide (Wegovy) - STEP Trials
Average weight loss: 15-20% of body weight over 68 weeks
For a 250 lb person: Expected loss of 37.5-50 lbs
- ~85% of patients lost at least 10% body weight
- ~50% lost at least 15% body weight
- ~30% lost at least 20% body weight
2Tirzepatide (Zepbound) - SURMOUNT Trials
Average weight loss: 20-25% of body weight over 72 weeks
For a 250 lb person: Expected loss of 50-62.5 lbs
- ~91% of patients lost at least 10% body weight
- ~73% lost at least 15% body weight
- ~57% lost at least 20% body weight
- Some patients achieved 25-30% weight loss at highest doses
📊 The Verdict on Weight Loss
Tirzepatide produces approximately 25-30% more weight loss than semaglutide in clinical trials. While both are highly effective, tirzepatide's dual mechanism gives it a statistical edge.
Side Effects Comparison
Both medications share similar side effects because they both target GLP-1 receptors. However, tirzepatide's dual mechanism may cause slightly more severe symptoms in some patients.
| Side Effect | Semaglutide | Tirzepatide |
|---|---|---|
| Nausea | 20-44% of patients | 25-48% of patients |
| Diarrhea | 30% of patients | 35% of patients |
| Constipation | 24% of patients | 20% of patients |
| Vomiting | 9-24% of patients | 12-28% of patients |
| Fatigue | Common | Common |
| Injection Site Reactions | Rare | Rare |
| Discontinuation Due to Side Effects | 4-7% | 6-10% |
💡 Managing Side Effects
- Both medications: Side effects typically worst in first 4-8 weeks, then improve significantly
- Starting slowly: Gradual dose escalation helps minimize nausea and GI issues
- Tirzepatide: Slightly higher discontinuation rate (6-10% vs 4-7%) suggests some patients find it harder to tolerate
- Individual variation: Some patients tolerate tirzepatide better than semaglutide, and vice versa
Cost Comparison
Brand Name Pricing
Semaglutide (Wegovy): $1,000-1,400/month without insurance
Tirzepatide (Zepbound): $1,000-1,400/month without insurance
Both medications cost roughly the same at brand name pricing. Insurance coverage varies widely.
Compounded Medication Pricing
Compounded Semaglutide: $150-400/month from online providers
Compounded Tirzepatide: $200-500/month from online providers
Compounded tirzepatide is slightly more expensive due to higher raw material costs and dual GIP/GLP-1 formulation complexity.
💰 Cost Verdict
Brand name: Essentially identical pricing. Compounded: Semaglutide is typically $50-100/month cheaper than tirzepatide. However, tirzepatide's superior weight loss results may offer better value per pound lost.
Which Medication Should You Choose?
Choose Semaglutide If:
- You want a proven medication with longer safety track record (FDA approved 2021)
- You prefer slightly lower side effect rates
- You're looking for the most affordable compounded option
- You have GI sensitivities and want to start conservatively
- 15-20% weight loss would meet your goals
- Your insurance covers Wegovy but not Zepbound
Choose Tirzepatide If:
- You want maximum weight loss results (20-25%+ body weight)
- You've tried semaglutide and need stronger effects
- You have significant weight to lose (>50 lbs)
- You're willing to manage potentially stronger side effects
- The additional cost is worth 25-30% more weight loss
- Your insurance covers Zepbound
Can You Switch Between Them?
Yes, many patients switch between semaglutide and tirzepatide based on results, side effects, or insurance coverage changes.
Switching from Semaglutide to Tirzepatide
- Common reason: Weight loss plateau after 6-12 months on semaglutide
- Typical protocol: Start tirzepatide at lowest dose even if on high-dose semaglutide
- Expected results: Additional 5-10% body weight loss in many cases
Switching from Tirzepatide to Semaglutide
- Common reasons: Side effects too severe, cost concerns, insurance changes
- Typical protocol: Start semaglutide at low dose to reassess tolerance
- Expected results: May maintain weight loss but unlikely to lose additional weight
⚠️ Always work with your healthcare provider when switching medications. Never combine both medications simultaneously.
The Bottom Line
Tirzepatide is objectively more effective for weight loss, producing 20-25% body weight reduction compared to semaglutide's 15-20%. The dual GIP/GLP-1 mechanism delivers superior results in clinical trials.
Semaglutide is more affordable and better tolerated by some patients, with a longer safety track record and slightly lower discontinuation rates due to side effects.
Both are revolutionary medications that dramatically outperform traditional weight loss methods. For many patients, either medication will produce life-changing results.
The "best" choice depends on your priorities: If maximum weight loss is the goal and you can tolerate potential side effects, choose tirzepatide. If you prioritize affordability and conservative treatment, choose semaglutide.
Consult with a qualified healthcare provider to determine which medication aligns with your medical history, weight loss goals, and tolerance for side effects.