What the Clinical Trials Show
All GLP-1 drugs reduce appetite and produce weight loss — but by very different amounts. Here's how the major options stack up based on their landmark clinical trials:
Tirzepatide (Zepbound / Mounjaro)
In the SURMOUNT-1 trial, participants on the highest dose of tirzepatide (15mg weekly) lost an average of 22.5% of their body weight over 72 weeks. In a head-to-head trial (SURMOUNT-5), tirzepatide users lost about 47% more total weight than semaglutide users.
Why Does Tirzepatide Work Better?
The short answer: it hits two targets instead of one. Tirzepatide is a "dual agonist" — it activates both the GLP-1 receptor and the GIP receptor (Glucose-dependent Insulinotropic Polypeptide). GIP is another gut hormone that works alongside GLP-1 to regulate appetite and fat metabolism. Activating both produces a stronger combined effect on hunger suppression and calorie burning than either one alone.
Semaglutide (Wegovy/Ozempic) only targets the GLP-1 receptor — which is still very effective, but not as powerful in trials.
But "Best" Is More Than Just Weight Loss Numbers
The drug with the highest average trial results isn't automatically the right choice for you. Here are the other factors that actually determine which GLP-1 is best in your situation:
Many insurers cover Ozempic for diabetes but not Wegovy for weight loss. Your out-of-pocket cost could vary by hundreds of dollars per month depending on what your plan covers.
Tirzepatide and semaglutide have similar side effect profiles (nausea, GI issues), but individuals respond differently. Some people tolerate one much better than the other.
If you have type 2 diabetes, your doctor may prefer Ozempic or Mounjaro because of their cardiovascular and blood sugar benefits specifically studied in diabetes populations.
Supply shortages have affected both semaglutide and tirzepatide at various points. Your local pharmacy's stock may influence the decision.
What About Compounded Semaglutide or Tirzepatide?
During supply shortages, many telehealth companies offered compounded (custom-made) versions of semaglutide and tirzepatide at lower prices. The FDA allowed this temporarily but has moved to restrict it as supplies stabilize. If you're considering a compounded GLP-1, ask your provider about the current regulatory status and the compounding pharmacy's certification.
The Bottom Line
If sheer weight loss effectiveness is the only criterion: tirzepatide (Zepbound for weight loss, Mounjaro for diabetes) wins based on the current clinical data. But the best GLP-1 for you depends on your insurance, your health history, and how your body responds. The right starting point is a conversation with your doctor — and possibly a quick quiz to see which programs prescribe which medications.