Based on published clinical trial data, tirzepatide (Zepbound/Mounjaro) produces the highest average weight loss at 22.5% of body weight (SURMOUNT-1, NEJM 2022). Semaglutide injectable (Wegovy) achieves 14.9% (STEP 1, NEJM 2021), and oral semaglutide (Oral Wegovy) achieves 15.1% (OASIS 1, Lancet 2023). All medications are available through Weight Method from $99/mo.
Ranked by Weight Loss
| # | Medication | Trial | Weight Loss | Year | Journal |
|---|---|---|---|---|---|
| 1 | Tirzepatide 15mg (Zepbound) | SURMOUNT-1 | 22.5% | 2022 | NEJM |
| 2 | Oral Semaglutide 50mg (Oral Wegovy) | OASIS 1 | 15.1% | 2023 | Lancet |
| 3 | Semaglutide 2.4mg (Wegovy) | STEP 1 | 14.9% | 2021 | NEJM |
| 4 | Tirzepatide 15mg — with T2D (Mounjaro) | SURMOUNT-2 | 14.7% | 2023 | Lancet |
| 5 | Semaglutide 2.4mg — with T2D (Ozempic) | STEP 2 | 9.6% | 2021 | Lancet |
| 6 | Oral Semaglutide 14mg (Rybelsus) | PIONEER 1 | 5-7% | 2019 | Lancet |
Tirzepatide 15mg (Zepbound)
Oral Semaglutide 50mg (Oral Wegovy)
Semaglutide 2.4mg (Wegovy)
Tirzepatide 15mg — with T2D (Mounjaro)
Semaglutide 2.4mg — with T2D (Ozempic)
Oral Semaglutide 14mg (Rybelsus)
Key Fact
Tirzepatide's 22.5% average weight loss in SURMOUNT-1 is the highest recorded in any GLP-1 clinical trial. As a dual GIP/GLP-1 agonist, it targets two incretin pathways — compared to semaglutide which targets GLP-1 alone.
Source: SURMOUNT-1, NEJM 2022; STEP 1, NEJM 2021
Top 3 in Detail
Tirzepatide (Zepbound / Mounjaro)
Tirzepatide is a dual GIP/GLP-1 agonist that targets two incretin pathways simultaneously. In the SURMOUNT-1 trial (NEJM 2022), participants on the 15mg dose achieved 22.5% mean body weight loss at 72 weeks. Brands: Zepbound (weight loss) and Mounjaro (type 2 diabetes). Weekly subcutaneous injection. Doses from 2.5mg to 15mg. Best for patients seeking maximum weight loss or those who haven't responded adequately to semaglutide.
Oral Semaglutide 50mg (Oral Wegovy)
The high-dose oral formulation of semaglutide eliminates the need for injections. In the OASIS 1 trial (Lancet 2023), the 50mg dose achieved 15.1% body weight loss. Same GLP-1 mechanism as injectable Wegovy, but as a daily pill. Best for patients who prefer oral medication or have needle aversion. FDA-approved in 2024.
Semaglutide 2.4mg Injectable (Wegovy)
Injectable semaglutide is the most-studied GLP-1 for weight loss. In the STEP 1 trial (NEJM 2021), the 2.4mg dose achieved 14.9% body weight loss at 68 weeks. Brands: Wegovy (weight loss) and Ozempic (type 2 diabetes, same molecule at lower dose). Weekly subcutaneous injection. Doses from 0.25mg to 2.4mg. The most established option with the longest track record of long-term data.
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Semaglutide
Same active ingredient as Ozempic® & Wegovy®. Proven to reduce body weight by up to 15%.
- Weekly injection
- Gradual dose increase
- Provider monitoring
- Free shipping
Tirzepatide
Same active ingredient as Mounjaro® & Zepbound®. Dual-action GLP-1/GIP for enhanced results.
- Weekly injection
- Dual hormone action
- Provider monitoring
- Free shipping