Semaglutide vs. Tirzepatide: Which Is Right for You?
Both medications produce significant weight loss. But they work differently, have different efficacy profiles, and may suit different patients. Here's an evidence-based comparison from a board-certified obesity medicine physician.
Quick Comparison
Semaglutide
Brand names: Wegovy® (weight loss), Ozempic® (diabetes)
Semaglutide is a GLP-1 receptor agonist that mimics a naturally occurring hormone released after eating. It signals satiety to your brain, reduces appetite, and slows gastric emptying. FDA-approved for weight loss in 2021, it's been the gold standard for GLP-1 weight loss therapy.
Tirzepatide
Brand names: Zepbound® (weight loss), Mounjaro® (diabetes)
Tirzepatide is a dual GIP/GLP-1 receptor agonist—the first of its kind. By activating two hormonal pathways instead of one, it produces greater appetite suppression and improved metabolic effects. FDA-approved for weight loss in 2023, it's shown unprecedented results in clinical trials.
Head-to-Head Comparison
How semaglutide and tirzepatide compare across key metrics based on clinical trial data.
| Metric | Semaglutide (Wegovy) | Tirzepatide (Zepbound) |
|---|---|---|
| Mechanism of Action | GLP-1 receptor agonist | Dual GIP + GLP-1 agonist |
| Average Weight Loss | ~15% of body weight | Up to 22.5% of body weight |
| Patients Losing ≥5% | 86% | 96% |
| Patients Losing ≥10% | 69% | 84% |
| Patients Losing ≥20% | ~32% | 57% |
| Maximum Dose | 2.4mg weekly | 15mg weekly |
| Titration Period | 16-20 weeks to max dose | 20+ weeks to max dose |
| A1c Reduction (Diabetic Patients) | ~1.5% | ~2.0% |
| FDA Approval for Weight Loss | June 2021 (longer track record) | November 2023 |
| Clinical Data | STEP trials (more extensive) | SURMOUNT trials |
Clinical Trial Results
Visualizing the weight loss outcomes from pivotal clinical trials.
Semaglutide (STEP 1 Trial)
Tirzepatide (SURMOUNT-1 Trial)
Sources: STEP 1 (N Engl J Med 2021) and SURMOUNT-1 (N Engl J Med 2022). Results at maximum doses with lifestyle intervention.
Side Effects Comparison
Both medications have similar GI side effects, though rates differ slightly.
Common Side Effects (Both)
- Nausea (typically improves after 2-4 weeks)
- Diarrhea or constipation
- Decreased appetite (this is the goal)
- Mild stomach discomfort
- Fatigue during dose titration
- Injection site reactions (rare)
Key Differences
- Nausea rates: Similar between both (~15-25%), though some patients tolerate one better than the other
- GI side effects: Generally comparable; slow titration helps with both
- Tirzepatide advantage: Some studies suggest slightly better tolerability at equivalent efficacy
- Individual variation: Response and tolerability vary significantly between patients
Who Should Consider Each?
While both are excellent options, certain factors may favor one over the other.
Consider Semaglutide If:
- You want a medication with a longer track record
- You've responded well to GLP-1s in the past
- You prefer more extensive long-term safety data
- Cost/insurance favors semaglutide for you
- You need a lower starting dose (more titration options)
Consider Tirzepatide If:
- You want maximum weight loss potential
- You've plateaued on semaglutide
- You have type 2 diabetes (superior A1c reduction)
- You didn't tolerate semaglutide well
- You want the dual-mechanism approach
The Bottom Line
Tirzepatide produces greater average weight loss in clinical trials—that's the data. But "average" doesn't mean it's right for everyone. Some patients respond exceptionally well to semaglutide. Others tolerate one medication better than the other.
The best choice depends on your health history, goals, insurance coverage, and how your body responds. That's why we don't just prescribe—we monitor, adjust, and optimize.
"I've seen patients lose 80+ pounds on semaglutide and others who needed to switch to tirzepatide to break through a plateau. The medication matters, but so does the monitoring. We track body composition with DEXA scans to make sure you're losing fat, not muscle—regardless of which GLP-1 you're on."
— Dr. Josh Lindsley, DO, DABOM
Frequently Asked Questions
Clinical trials show tirzepatide produces greater average weight loss (up to 22.5%) compared to semaglutide (15%). In the SURMOUNT-3 head-to-head trial, tirzepatide users lost approximately 5% more body weight. However, individual response varies significantly—some patients respond better to semaglutide.
Yes, switching is possible and sometimes recommended if you've plateaued on semaglutide or experienced tolerability issues. Your physician will typically start tirzepatide at a lower dose and titrate up. There's no waiting period required between medications.
Brand-name pricing is similar ($900-1,200/month without insurance). Insurance coverage varies by plan. At Highland Longevity, compounded GLP-1 therapy starts at $199/month, making both medications accessible regardless of insurance status.
Both can lead to muscle loss if nutrition isn't optimized—up to 40% of weight lost can be lean mass. This is why we monitor body composition with DEXA scans and work with our registered dietitian to ensure adequate protein intake and preserve muscle mass.
The best medication depends on your health history, weight loss goals, insurance coverage, and individual response. During your consultation, we'll review your medical history, discuss your goals, and recommend the option most likely to work for you. We can also adjust course based on your response.
Ready to Start Your Weight Loss Journey?
Book a consultation to discuss which GLP-1 medication is right for you. We'll create a personalized protocol with body composition tracking and ongoing optimization.