With multiple GLP-1 medications on the market, which one actually produces the most weight loss? We've ranked them based on clinical trial data, real-world results, cost, and availability.
💡 Quick Answer: Tirzepatide (Zepbound/Mounjaro) produces the most weight loss in clinical trials — about 20-25% of body weight vs 15% for semaglutide. However, semaglutide is cheaper and more available. For most people, either medication will produce significant results.
The Rankings
Tirzepatide (Zepbound/Mounjaro)
The dual GLP-1/GIP agonist that outperforms all other options in clinical trials. Best choice if maximum weight loss is your priority and cost isn't a major concern.
Semaglutide (Wegovy/Ozempic)
The original GLP-1 blockbuster. Excellent weight loss, more affordable than tirzepatide, better availability. The smart choice for budget-conscious patients.
Oral Semaglutide (Rybelsus)
Daily pill instead of weekly injection. Less effective than injectable forms and strict dosing requirements (empty stomach, no food/drink for 30 min). Best for needle-phobic patients.
Liraglutide (Saxenda)
Older daily injection. Less effective than newer options and requires daily dosing. Generally not recommended when semaglutide/tirzepatide are available.
Head-to-Head: The Clinical Data
Weight Loss Comparison
Based on the landmark clinical trials (STEP and SURMOUNT):
- Tirzepatide 15mg: 20.9% average body weight loss (SURMOUNT-1)
- Semaglutide 2.4mg: 14.9% average body weight loss (STEP 1)
- Oral Semaglutide 50mg: ~15% body weight loss (OASIS 1)
- Liraglutide 3mg: 8% average body weight loss (SCALE)
What This Means in Pounds
For a 200-pound person:
- Tirzepatide: ~42 pounds lost
- Semaglutide: ~30 pounds lost
- Oral semaglutide: ~30 pounds lost
- Liraglutide: ~16 pounds lost
Beyond Weight Loss: Other Benefits
Tirzepatide Advantages
- Superior A1C reduction for diabetics (2.0-2.3%)
- May preserve more lean muscle during weight loss
- Cardiovascular benefits (ongoing studies)
Semaglutide Advantages
- Proven cardiovascular benefits (SELECT trial)
- Longer safety track record (FDA approved 2017)
- More affordable and available
- Oral option available
Which Should You Choose?
Choose Tirzepatide If:
- Maximum weight loss is your top priority
- You have significant insulin resistance or type 2 diabetes
- Budget allows $199-399/month
- You've plateaued on semaglutide
Choose Semaglutide If:
- You want proven results at a lower cost
- Budget is a primary concern ($149-249/month)
- You value the longer safety track record
- Your insurance covers it (more common than tirzepatide)
The Practical Reality
Here's the truth: both medications produce life-changing weight loss. The difference between 15% and 20% matters less than whether you can afford and access the medication long-term.
A 15% weight loss maintained for years beats a 20% weight loss you can't afford after 6 months.
What About Side Effects?
Both medications cause similar GI side effects:
- Nausea (40-50% of users, usually temporary)
- Vomiting (20-30%)
- Diarrhea (15-25%)
- Constipation (15-25%)
Clinical trials suggest tirzepatide may cause slightly more GI symptoms at higher doses, but individual responses vary significantly. Some patients tolerate one better than the other — if you have issues with one, switching may help.
The Bottom Line
For maximum effectiveness: Tirzepatide (Zepbound/Mounjaro) wins on pure weight loss numbers.
For best overall value: Semaglutide (Wegovy/Ozempic) offers excellent results at a lower price with better availability.
The real answer: The best GLP-1 is the one you can afford and access consistently. Both are transformative medications. Pick based on your budget, insurance, and availability — then commit to it long-term.