Editorially reviewed · Last updated September 8, 2026 · How we review
Part of How-To Guides.
Key findings
- Start with approval status and the evidence, then compare health outcomes, route, side effects, and access.
- Results from separate trials provide context but are not a direct head-to-head treatment ranking.
- Semaglutide, tirzepatide, and orforglipron (Foundayo) have approved products; retatrutide and CagriSema remain investigational.
- SURMOUNT-5 and REDEFINE 4 provide direct comparisons for their studied treatments and populations. TRIUMPH-5 results are pending.
GLP-1 Drug Comparison Tool
Compare GLP-1 and incretin-based weight loss drugs side by side. Select two or three drugs to compare receptor activity, selected trial results, administration, and approval status.
GLP-1 Drug Comparison Tool
Select two or three drugs to view their trial results and approval status. Remove a selected drug before adding another.
Selected trial weight loss
These are average results from separate trials, with different doses, durations and analyses. They do not rank the drugs or predict your weight loss. See the study details below.
| Feature | Retatrutide | Tirzepatide | Semaglutide |
|---|---|---|---|
| Type | Triple | Dual | Single |
| Brand Names | Not yet named | Zepbound, Mounjaro | Wegovy, Ozempic, Rybelsus |
| Manufacturer | Eli Lilly | Eli Lilly | Novo Nordisk |
| Mechanism | GLP-1 + GIP + glucagon triple receptor agonist | GLP-1 + GIP dual receptor agonist | GLP-1 receptor agonist |
| Receptors | GLP-1, GIP, Glucagon | GLP-1, GIP | GLP-1 |
| FDA Status | Investigational | FDA approved | FDA approved |
| Selected trial weight loss | -28.3% (80 weeks) | -22.5% (72 weeks) | -14.9% (68 weeks) |
| Key Trial | TRIUMPH-1 | SURMOUNT-1 | STEP 1 |
| Study dose | 12 mg weekly injection (investigational) | 15 mg weekly injection | 2.4 mg weekly injection |
| Study population | Adults with obesity or overweight and a related condition, without diabetes | Adults with obesity or overweight and a related condition, without diabetes | Adults with obesity or overweight and a related condition, without diabetes |
| Analysis | Efficacy estimand: assumes continued treatment without prohibited weight-management therapy | Efficacy estimand: estimates effects before treatment discontinuation | Treatment-policy estimand: includes treatment discontinuation and rescue intervention |
| Schedule | Once weekly injection in trials | Once weekly (injection) | Once weekly (injection) or daily (oral), depending on product |
| Oral Option | No | No | Yes |
| Key consideration | Investigational; no FDA-approved product or dose. Source | Approved weekly injection; the indication depends on the brand. Source | Wegovy also has oral and higher-dose injectable options; the selected result is for 2.4 mg injection. Source |
Disclaimer: Weight loss results are from separate clinical trials with different populations and cannot be directly compared. Head-to-head trials compare treatments within a defined study population. This tool is for informational purposes only and does not constitute medical advice.
Understanding the Drug Classes
GLP-1 and incretin-based drugs fall into distinct categories based on how many receptors they target:
Swipe sideways to see every column.
| Type | Receptors | Drugs | Selected Trial Result |
|---|---|---|---|
| Single agonist | GLP-1 | Semaglutide (Ozempic/Wegovy), Orforglipron (Foundayo) | -14.9% (STEP 1) |
| Dual agonist | GLP-1 + GIP | Tirzepatide (Mounjaro/Zepbound) | -22.5% (SURMOUNT-1) |
| Triple agonist | GLP-1 + GIP + Glucagon | Retatrutide | -28.7% (TRIUMPH-4) |
| Combination | Amylin + GLP-1 | CagriSema | -22.7% (REDEFINE 1) |
These selected results come from different trials and are not class-wide maximums. Formulation, dose, population, duration, and estimand matter; receptor count is not a treatment ranking.
Head-to-Head Trials
Only head-to-head trials can definitively compare drugs. Cross-trial comparisons (different patient populations, entry criteria, and trial lengths) are inherently limited.
Swipe sideways to see every column.
| Trial | Drug A | Drug B | Result |
|---|---|---|---|
| SURMOUNT-5 | Tirzepatide: -20.2% | Semaglutide: -13.7% | Tirzepatide superior |
| SURPASS-2 (T2D) | Tirzepatide | Semaglutide 1 mg | Tirzepatide superior at studied doses; not a comparison with all current semaglutide doses |
| TRIUMPH-5 | Retatrutide | Tirzepatide | Results pending |
| REDEFINE 4 (84 weeks) | CagriSema: -23.0% | Tirzepatide: -25.5% | Efficacy estimand; CagriSema noninferiority not met |
Detailed Comparison Articles
For in-depth comparisons between specific drugs:
GLP-1 vs GLP-1 Comparisons
- Zepbound vs Wegovy — the two leading weight loss drugs head-to-head
- Tirzepatide vs Semaglutide — the generic comparison with full clinical data
- Mounjaro vs Ozempic — brand-focused practical comparison
- Ozempic vs Wegovy — same drug, different purpose
Retatrutide Comparisons
- Retatrutide vs Tirzepatide — triple vs dual agonist
- Retatrutide vs Wegovy — triple agonist vs GLP-1
- Retatrutide vs Zepbound — next-gen vs current best
- Retatrutide vs CagriSema — triple agonist vs amylin combo
- Retatrutide vs Orforglipron — injectable vs oral
Overview
- Which GLP-1 Is Best for Weight Loss? — decision framework by patient priority
Frequently Asked Questions
Which GLP-1 drug produces the most weight loss?
SURMOUNT-5 directly favored tirzepatide over semaglutide 1.7/2.4 mg at 72 weeks. It did not test every current medicine or formulation. Retatrutide has reported substantial Phase 3 results but remains investigational; its trial averages cannot establish superiority over approved options.
Can you compare drugs from different clinical trials?
They provide context, but different populations, doses, durations, and estimands prevent a direct treatment ranking. SURMOUNT-5 and REDEFINE 4 are direct comparisons for the treatments and populations they studied; neither establishes the effect of switching to retatrutide.
What is a triple agonist?
A triple agonist activates three receptors. Retatrutide targets GLP-1, GIP, and glucagon. This describes receptor activity, not a guarantee of better efficacy or safety.
Is there an oral GLP-1 for weight loss?
Sources
-
NEJM. SURMOUNT-5.
-
Novo Nordisk. REDEFINE 4.
-
Jastreboff, A.M., et al. (2022). SURMOUNT-1 (tirzepatide for obesity). NEJM. DOI: 10.1056/NEJMoa2206038
-
Wilding, J.P.H., et al. (2021). STEP 1 (semaglutide for obesity). NEJM. DOI: 10.1056/NEJMoa2032183
-
Eli Lilly. (2025). TRIUMPH-4 Results. Press release.
-
Garvey, W.T., et al. (2025). REDEFINE 1 (CagriSema). NEJM. DOI: 10.1056/NEJMoa2502081
- What this is
- Educational information, not medical advice. It reports published research — it doesn’t recommend that you use, obtain, or supply anything.
- Regulatory status
- Semaglutide, tirzepatide and orforglipron have FDA-approved prescription products. Retatrutide and CagriSema remain investigational. Indications and dosing depend on the product.
- Our standard
- Every claim traces to a primary source. We label the strength of evidence and flag estimates as estimates — never as clinical fact.
- No commercial ties
- We don’t sell, supply, or link to suppliers of any medicine, and aren’t affiliated with any manufacturer.
Do not make decisions about your health without consulting a qualified healthcare provider. For trial enrolment, see ClinicalTrials.gov. More on how we review.
Sources
NEJM
The Lancet
JAMA
FDA
ClinicalTrials.govRelated reading
Which GLP-1 Is Best for Weight Loss? All Five Drugs Compared
Compare approved options and investigational drugs by direct trial evidence, indication, safety, oral or injectable route, and access.
Zepbound vs Wegovy: Which One Actually Works Better in 2026?
Zepbound produced -20.2% vs Wegovy's -13.7% weight loss in the SURMOUNT-5 head-to-head trial. Full comparison of cost, side effects, and CV data.
Tirzepatide vs Semaglutide: Complete Comparison (2026 Data)
Tirzepatide vs semaglutide with SURMOUNT-5 head-to-head data: -20.2% vs -13.7% weight loss. Full comparison of efficacy, side effects, and access.
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