Retatrutide vs Zepbound: What's the Difference?
Zepbound is the brand name for tirzepatide, Eli Lilly's FDA-approved dual agonist (GLP-1 + GIP) for obesity. Retatrutide is Lilly's investigational triple agonist (GLP-1 + GIP + Glucagon) currently in Phase 3 trials.
Both are made by the same company and given as weekly injections. Retatrutide adds a third receptor (glucagon) that increases energy expenditure, producing approximately 6 percentage points more weight loss than Zepbound.
For the detailed comparison, see Retatrutide vs Tirzepatide (Zepbound).
Quick Comparison
| Retatrutide | Zepbound (Tirzepatide) | |
|---|---|---|
| Receptors | GLP-1 + GIP + Glucagon (triple) | GLP-1 + GIP (dual) |
| Max weight loss | -28.7% at 68 weeks (12 mg) | -22.5% at 72 weeks (15 mg) |
| FDA status | Not approved (Phase 3) | Approved (November 2023) |
| Also sold as | No brand name yet | Mounjaro (for type 2 diabetes) |
| Monthly cost | Not available (~$1,200–1,500 projected) | ~$1,060/month |
| Discontinuation (AEs) | 18.2% | 10.5% |
| Unique side effect | Dysesthesia (20.9%) | Gallbladder/biliary risk |
Why Retatrutide Produces More Weight Loss
Zepbound targets two receptors: GLP-1 (appetite suppression) and GIP (metabolic efficiency). Retatrutide targets all three, adding glucagon receptor activation which:
- Increases resting energy expenditure through thermogenesis
- Promotes breakdown of stored fat, particularly liver fat
- Adds a "burn more" mechanism on top of the "eat less" effect
This is why retatrutide achieves ~29% weight loss vs Zepbound's ~22.5%.
Weight Loss Thresholds
| Threshold | Retatrutide 12 mg | Zepbound 15 mg |
|---|---|---|
| Lost at least 15% | 83.2% | 73% |
| Lost at least 20% | 72.5% | 63% |
| Lost at least 25% | 58.6% | 39.7% |
For a 250-lb person: retatrutide produces approximately 16 more pounds of weight loss than Zepbound (~72 lbs vs ~56 lbs).
The TRIUMPH-5 Head-to-Head Trial
Eli Lilly's TRIUMPH-5 (NCT06662383) is currently enrolling approximately 800 participants to directly compare retatrutide against tirzepatide (the active ingredient in Zepbound). Results are expected around April 2027. This will provide the first definitive head-to-head comparison.
Availability
| Retatrutide | Zepbound | |
|---|---|---|
| Available now | No — clinical trials only | Yes — by prescription |
| Expected availability | Q4 2027 – Q1 2028 | Available since Nov 2023 |
| Insurance coverage | N/A | Growing — check with your plan |
Frequently Asked Questions
Is retatrutide replacing Zepbound?
No. Lilly is developing both drugs for different patient needs. Zepbound is available now with strong efficacy and an established safety profile. Retatrutide will be the option for patients seeking maximum weight loss or those with conditions where the glucagon mechanism adds specific benefit (e.g., fatty liver disease).
Should I wait for retatrutide or start Zepbound now?
If you qualify for Zepbound, starting now is reasonable. Retatrutide won't be available until late 2027 at the earliest. Talk to your doctor about your options.
Is Zepbound the same as Mounjaro?
Yes — both are tirzepatide made by Eli Lilly. Zepbound is for obesity/weight loss. Mounjaro is for type 2 diabetes. Same molecule, different brand names for different indications.
Sources
- Eli Lilly. (2025). TRIUMPH-4 results. Press release.
- Jastreboff, A.M., et al. (2022). Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). NEJM. DOI: 10.1056/NEJMoa2206038.
- ClinicalTrials.gov. TRIUMPH-5 (NCT06662383). Lilly Trial Guide.
Medical Disclaimer
The content on glp3.wiki is for informational purposes only and does not constitute medical advice, diagnosis, or treatment. Retatrutide is an investigational drug. Zepbound is FDA-approved for specific indications.
Do not use this information to make decisions about your health without consulting a qualified healthcare provider.
This site is not affiliated with Eli Lilly and Company or any pharmaceutical manufacturer.
Sources
- SURMOUNT-1 trial (tirzepatide)
NEJM
- TRIUMPH-5 head-to-head trial
Lilly Trial Guide
Related reading
Zepbound vs Wegovy: Which Weight Loss Drug Is Better?
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.
Retatrutide vs Tirzepatide (Zepbound): Triple Agonist vs Dual Agonist
Retatrutide produces 28.7% weight loss (triple agonist) vs tirzepatide's 22.5% (dual agonist). A head-to-head trial is underway.
What Is Retatrutide (GLP-3)?
The world's first triple agonist weight loss drug — how it works, what the trials show, and why people call it GLP-3.