There's No Universal "Best"—Here's Why
If you're looking for a simple answer about which GLP-1 medication is best for weight loss, we can't give you one. The clinical trials show tirzepatide produces higher average weight loss than semaglutide, but "best" depends on factors trials don't measure: your insurance coverage, tolerance for side effects, access to specific medications, and cost constraints.
What we can do is show you what the evidence says, what each medication costs, and what practical factors matter when choosing between them.
The Clinical Trial Evidence
Two major trial programs tested GLP-1 medications specifically for weight management in people without diabetes: SURMOUNT (tirzepatide) and STEP (semaglutide).
Head-to-Head Comparison
| Medication | Trial | Weight Loss | Duration | ≥5% Loss |
|---|---|---|---|---|
| Tirzepatide 15mg | SURMOUNT-1 | 20.9% | 72 weeks | 91% |
| Tirzepatide 10mg | SURMOUNT-1 | 15.0% | 72 weeks | 85% |
| Semaglutide 2.4mg | STEP 1 | 14.9% | 68 weeks | 86% |
| Oral Semaglutide 25mg | OASIS 4 | 17.4% | 68 weeks | 76% |
| Placebo (combined) | — | 2-3% | — | ~30% |
These are averages from separate trials with different participant populations. Direct head-to-head comparison trials are limited.
What the Numbers Mean
Tirzepatide 15mg produced the highest average weight loss at 20.9%, about 6 percentage points more than semaglutide 2.4mg at 14.9%. For someone weighing 220 pounds:
- Tirzepatide 15mg: Average loss of 46 pounds
- Semaglutide 2.4mg: Average loss of 33 pounds
- Oral Semaglutide 25mg: Average loss of 38 pounds
These are averages. Individual results in the trials ranged from minimal loss to over 25% body weight reduction. The only way to know how you'll respond is to try the medication under medical supervision.
Why Tirzepatide May Show Higher Weight Loss
Tirzepatide is a dual agonist—it activates both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptors. Semaglutide only activates GLP-1 receptors. The dual mechanism may explain the higher average weight loss, though research on exactly how GIP contributes is ongoing.
Both medications work primarily by reducing appetite and slowing gastric emptying. The weight loss effect comes from eating less, not from increasing metabolism or blocking calorie absorption.
Side Effects Comparison
Both medications share similar side effect profiles, dominated by gastrointestinal issues.
Tirzepatide (SURMOUNT-1)
- Nausea31%
- Diarrhea23%
- Vomiting11%
- Constipation17%
- Discontinued due to side effects6.2%
Semaglutide (STEP 1)
- Nausea44%
- Diarrhea30%
- Vomiting24%
- Constipation24%
- Discontinued due to side effects7.0%
Semaglutide showed slightly higher rates of nausea, diarrhea, and vomiting in the STEP 1 trial compared to tirzepatide in SURMOUNT-1. Discontinuation rates due to side effects were similar (6-7%). Both medications carry the same serious risk warnings for pancreatitis, gallbladder problems, and thyroid tumors (based on rodent studies).
Cost Comparison
Brand-name pricing is similar and expensive. Compounded versions offer significant savings.
| Medication | Brand-Name | Compounded | Availability |
|---|---|---|---|
| Tirzepatide (injectable) | $1,000+/month | $249-500/month | Limited brand supply |
| Semaglutide (injectable) | $1,300+/month | $99-300/month | Better brand availability |
| Semaglutide (oral) | $149+/month | Not yet available | Launches Jan 2026 |
Insurance coverage varies widely. Some plans cover these medications for diabetes but not weight loss. Others require extensive prior authorization. Compounded versions are cash-pay only but significantly cheaper.
Access and Availability
Semaglutide Has More Options
- Injectable Wegovy/Ozempic: Available through traditional pharmacies and telehealth
- Oral Wegovy: Launching January 2026 with lower starting price
- Compounded semaglutide: Widely available through multiple telehealth platforms
Tirzepatide Has Fewer Pathways
- Injectable Mounjaro/Zepbound: Brand-name supply has been limited
- Compounded tirzepatide: Available but fewer providers than compounded semaglutide
- No oral version: Injectable only for now
Which Should You Choose?
The trial data suggests tirzepatide produces higher average weight loss. But several practical factors matter more than the 6-percentage-point difference in trial results:
Decision Framework
Consider Tirzepatide If:
- ✓You want the medication with highest average weight loss in trials
- ✓You can afford brand-name or have insurance coverage for Mounjaro/Zepbound
- ✓You're comfortable with compounded medications and can find a provider
- ✓You don't mind weekly injections (no oral option available)
Consider Semaglutide If:
- ✓You want more access options (injectable + oral formulation coming)
- ✓You prefer compounded medication with more provider choices
- ✓You want the option to switch to oral dosing in 2026
- ✓You're paying cash and want lowest compounded prices ($99-300/month)
- ✓You're okay with 14.9% average weight loss vs 20.9%
How to Access These Medications
Most people without insurance coverage access GLP-1 medications through telehealth platforms offering compounded versions. Here's how they compare:
Compounded Semaglutide
Most affordable GLP-1 option
Top Provider: Coreage RX
- ✓503B FDA-registered compounding pharmacy
- ✓Third-party testing for quality assurance
- ✓Transparent pricing, fast delivery (24-48 hours)
- ✓Medical oversight and dosing support
We earn a commission if you use our links. Doesn't affect our recommendations.
Compounded Tirzepatide
Highest weight loss potential
Available Through Multiple Providers
- •Coreage RX, Hims & Hers, Ro all offer compounded tirzepatide
- •Higher cost than compounded semaglutide but still 50-75% less than brand
- •20.9% average weight loss in clinical trials
The Bottom Line
Based purely on clinical trial data, tirzepatide produces the highest average weight loss at 20.9% versus semaglutide's 14.9%. That's a meaningful difference—about 6 percentage points or roughly 13 additional pounds for someone weighing 220 pounds.
But "best" depends on more than average trial results. Semaglutide offers:
- Lower compounded prices ($99-300 vs $249-500 monthly)
- More telehealth provider options
- Oral formulation launching January 2026
- Better brand-name availability if you have insurance
Tirzepatide offers higher average weight loss but fewer access pathways and higher compounded costs.
For most people paying out of pocket, compounded semaglutide through a provider like Coreage RX ($99-300/month) offers the best combination of proven efficacy, low cost, and reliable access. If maximizing weight loss potential is your priority and cost isn't a barrier, compounded tirzepatide produces higher average results.
Talk to a healthcare provider about which makes sense for your specific situation. Both medications require medical supervision and ongoing monitoring.
Related Resources
Semaglutide Complete Guide
STEP trial results, dosing, side effects, and costs
Tirzepatide Complete Guide
SURMOUNT trial results, mechanism, and availability
Full Medication Comparison
Side-by-side data for all GLP-1 medications
Provider Comparison
Compare telehealth platforms offering GLP-1 prescriptions
🇺🇸Medical Disclaimer
Your health, your doctor. This article compares clinical trial data for educational purposes. It is not medical advice. GLP-1 medications are prescription drugs requiring physician oversight. We're not healthcare providers and cannot recommend which medication is appropriate for you.
Clinical trial results represent averages and don't predict individual outcomes. Talk to your doctor about potential risks, benefits, and which GLP-1 medication makes sense for your specific health situation. We earn affiliate commissions from some providers mentioned.