Semaglutide and tirzepatide are the two dominant GLP-1 medications in 2026. Both cause significant weight loss, but they work differently, cost differently, and have distinct side effect profiles. Here's the updated comparison.
Mechanism of Action
Semaglutide (Wegovy, Ozempic, compounded) is a GLP-1 receptor agonist. It mimics the GLP-1 hormone, slowing gastric emptying, reducing appetite, and improving insulin sensitivity.
Tirzepatide (Zepbound, Mounjaro, compounded) is a dual GIP/GLP-1 receptor agonist. It activates both the GLP-1 and GIP receptors, which may explain its higher average weight loss in clinical trials.
Efficacy Head-to-Head
| Metric | Semaglutide 2.4mg | Tirzepatide 15mg |
|---|---|---|
| Avg Weight Loss | ~15% (STEP 1) | ~21% (SURMOUNT-1) |
| Trial Duration | 68 weeks | 72 weeks |
| ≥10% Weight Loss | ~69% | ~89% |
| ≥20% Weight Loss | ~32% | ~56% |
Side Effects
Both medications share common GI side effects: nausea, diarrhea, vomiting, constipation, and abdominal pain. These are typically worst during dose titration and improve over time. Tirzepatide's dual-receptor mechanism may produce slightly different GI patterns in some patients, but head-to-head tolerability data is limited.
Cost Comparison (Self-Pay, June 2026)
| Option | Semaglutide | Tirzepatide |
|---|---|---|
| Brand-name (list price) | $1,349/mo (Wegovy) | $1,059/mo (Zepbound) |
| Compounded (telehealth avg) | $99–$199/mo | $149–$299/mo |
| Foundayo (oral, different drug) | N/A | N/A |
Sunlight $159/mo sema, $239/mo tirz · LegitScript certified. Flat pricing — $159 first month, $179 ongoing (semaglutide). No membership, free shipping, HSA/FSA.
⚕️ Compounded medications are not FDA-approved. They are prepared by licensed pharmacies under physician supervision.
Embody From $149/mo · Injectable semaglutide with coaching included. LegitScript-certified 503B pharmacy sourcing. Strong onboarding support.
⚕️ Compounded medications are not FDA-approved. They are prepared by licensed pharmacies under physician supervision.
How to Choose
Choose semaglutide if: cost is your primary concern (compounded sema is generally cheaper), you want the most-studied GLP-1 with the longest track record, or you're eligible for oral semaglutide and want to avoid injections.
Choose tirzepatide if: you want maximum average weight loss, you've tried semaglutide and plateaued, or you have type 2 diabetes (tirzepatide's dual mechanism may offer better glycemic control).
⚕️ Compounded medications are not FDA-approved. They are prepared by licensed pharmacies under physician supervision.