Zepbound (tirzepatide) and retatrutide are both Eli Lilly weight-loss injectables, but only one of them is available. Zepbound is FDA-approved and produced about 20.9% average weight loss at its top dose in the SURMOUNT-1 trial. Retatrutide is still investigational (in phase 3 as of 2026, not approved anywhere), and it has posted larger numbers in trials: 24.2% at 48 weeks in phase 2 and up to 28.3% at 80 weeks in the phase 3 TRIUMPH-1 study. The short version: retatrutide looks more powerful on paper, but you cannot get it through a pharmacy yet, while Zepbound is on shelves today.
This comparison breaks down how the two drugs differ on mechanism, weight-loss data, dosing, side effects, price, and availability so you can see exactly where each one stands.
Quick comparison table
| Feature | Retatrutide | Zepbound (tirzepatide) |
|---|---|---|
| Maker | Eli Lilly | Eli Lilly |
| Drug class | Triple agonist (GLP-1, GIP, glucagon) | Dual agonist (GLP-1, GIP) |
| Approval status | Investigational, phase 3 (not FDA-approved) | FDA-approved for obesity (Nov 2023) |
| Peak trial weight loss | 24.2% at 48 wk (phase 2); up to 28.3% at 80 wk (phase 3) | 20.9% at 72 wk (SURMOUNT-1, 15 mg) |
| Dosing | Once-weekly injection, up to 12 mg | Once-weekly injection, up to 15 mg |
| Route | Subcutaneous self-injection | Subcutaneous self-injection |
| List price | Not commercially priced | About $1,059.87/month |
| Availability | Clinical trials only | Retail pharmacies in the US |
Mechanism: dual agonist vs triple agonist
The core difference is how many gut and metabolic hormone pathways each drug activates.
Zepbound's active ingredient, tirzepatide, is a dual agonist. It mimics two hormones at once: GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide). GLP-1 slows gastric emptying, blunts appetite, and improves how the body handles glucose. Adding GIP appears to amplify the appetite and metabolic effects beyond what GLP-1 alone delivers, which is part of why tirzepatide outperformed older single-agonist drugs like semaglutide.
Retatrutide is a triple agonist. It hits GLP-1 and GIP like tirzepatide, then adds a third target: the glucagon receptor. Glucagon receptor activation is the interesting twist here. Glucagon raises energy expenditure and helps mobilize stored fat, including liver fat. The theory is that pairing appetite suppression (from GLP-1 and GIP) with increased energy burn (from glucagon) drives more total weight loss. The phase 2 and phase 3 numbers so far support that theory.
If you want the deeper biology, see our guide to retatrutide's mechanism of action and the overview of what retatrutide is.
Weight loss: what the trials actually show
Both drugs have strong clinical data, but they come from separate trials with different lengths and patient groups, so the percentages are not a perfectly head-to-head match. There has been no direct trial pitting retatrutide against Zepbound. Here is what each program reported.
Zepbound (SURMOUNT-1)
SURMOUNT-1 enrolled 2,539 adults with obesity (or overweight plus a weight-related condition) and no diabetes. Participants took tirzepatide or placebo once weekly for 72 weeks. Average weight reduction by week 72:
- 15 mg: 20.9%
- 10 mg: 19.5%
- 5 mg: about 15%
- Placebo: 3.1%
That result is the foundation of Zepbound's FDA approval for chronic weight management.
Retatrutide (phase 2)
The phase 2 trial (published in the New England Journal of Medicine, Jastreboff et al., 2023) enrolled 338 adults with obesity or overweight without type 2 diabetes and ran for 48 weeks. Least-squares mean weight change at 48 weeks:
- 12 mg: -24.2%
- 8 mg: -22.8%
- 4 mg: -17.1%
- 1 mg: -8.7%
- Placebo: -2.1%
At the 12 mg dose, 83% of participants lost at least 15% of their body weight, and the curve had not clearly plateaued at 48 weeks, suggesting more loss might be possible with longer treatment.
Retatrutide (phase 3 TRIUMPH-1)
The first pivotal phase 3 readout, TRIUMPH-1, reported in December 2025. Over 80 weeks, weight loss was:
- 12 mg: 28.3% (about 70.3 lbs)
- 9 mg: 25.9% (about 64.4 lbs)
- 4 mg: 19.0% (about 47.2 lbs)
- Placebo: 2.2%
Notably, 45.3% of people on 12 mg lost at least 30% of their body weight, a threshold historically associated with bariatric surgery. In an extended-follow-up subgroup with BMI of 35 or higher who stayed on treatment to 104 weeks, 12 mg reached about 30.3%.
For a fuller breakdown of the trial program, see our retatrutide clinical trial summary and the before-and-after overview.
Reading the numbers fairly
Retatrutide's headline figures are higher, but keep the caveats in mind:
- The trials differ in length (48 to 80 weeks vs 72 weeks) and dose ceilings.
- Cross-trial comparisons are not the same as a head-to-head study.
- Retatrutide's phase 3 results are recent and still being peer-reviewed and submitted.
Even with those caveats, the consistent signal across phase 2 and phase 3 is that retatrutide produces more weight loss than the best dual-agonist data to date. Our retatrutide vs tirzepatide article looks at the molecule-level comparison in more detail.
Dosing and titration
Both are once-weekly subcutaneous injections you give yourself, and both use slow dose escalation to limit nausea.
Zepbound starts at 2.5 mg once weekly, then increases by 2.5 mg roughly every four weeks as tolerated. The titration ladder is 2.5 to 5 to 7.5 to 10 to 12.5 to 15 mg, with 15 mg the maximum maintenance dose. Many people settle at 10 or 15 mg for maintenance.
Retatrutide dosing in trials also ramped up slowly. The phase 2 study used a lower 2 mg start (instead of 4 mg) specifically because it reduced gastrointestinal side effects, then escalated toward target doses of 4, 8, or 12 mg. Because retatrutide is not approved, there is no official prescribing label or finalized dose schedule yet. For what the trials used, see our retatrutide dosage guide, the dosage chart, and the dosing schedule.
Side effects
The side-effect profiles look similar because both drugs lean heavily on GLP-1 and GIP, and gastrointestinal symptoms dominate.
Common side effects for both include:
- Nausea (reported in roughly 30 to 40% of users in tirzepatide data)
- Diarrhea
- Vomiting
- Constipation
- Stomach (abdominal) pain
- Reduced appetite
For both drugs, these effects are usually mild to moderate, are most noticeable after a dose increase, and tend to ease as the body adjusts. Slower titration and a lower starting dose reduce them.
Retatrutide's glucagon activity adds a few things to watch that are less central to Zepbound. In trials, retatrutide was associated with dose-dependent increases in heart rate and some transient changes in glucose handling at higher doses, which is expected from glucagon receptor activity. Longer phase 3 data will clarify how meaningful these are. For details, see retatrutide side effects and our take on whether retatrutide is safe.
Price and access
This is where the two drugs split sharply.
Zepbound has a US list price of about $1,059.87 per month across all dose strengths. Commercially insured patients whose plans cover it may pay as little as $25 per month with Lilly's savings card, and Lilly also sells lower-cost single-dose vials directly in some cases. Coverage varies widely by plan, and many insurers still restrict obesity drugs.
Retatrutide has no commercial price because it is not for sale. In the official supply chain it is legally available only to people enrolled in Lilly's clinical trials. Any product marketed as "retatrutide" outside a trial is compounded or research-grade material that has not been through FDA review, and quality and legality are not guaranteed. We cover this in compounded retatrutide, retatrutide without a prescription, and where to buy retatrutide. For projected pricing once approved, see retatrutide cost.
Availability and approval status
Zepbound was approved by the FDA in November 2023 for chronic weight management in adults with obesity, or overweight plus at least one weight-related condition. You can get it with a prescription at US pharmacies today.
Retatrutide is investigational. As of mid-2026 it is not approved by the FDA, the EMA, or any other major regulator. It is in a multi-trial phase 3 program (called TRIUMPH), with several more readouts expected through 2026 covering obesity, type 2 diabetes, sleep apnea, liver disease, and cardiovascular outcomes. Analysts expect a possible FDA submission in late 2026 or early 2027, which would put a potential approval no earlier than late 2027, though Lilly has not confirmed any timeline. See when retatrutide will be available for the latest.
Which should you consider?
- If you want a proven, prescribable option now: Zepbound is the only one of the two you can actually obtain through normal channels, and its 72-week data is robust.
- If you are tracking the next generation: Retatrutide's triple-agonist mechanism and larger trial numbers make it the most-watched obesity drug in development, but it is not available outside trials and its full safety record is still being built.
- If you have not started any GLP-1 yet: Talk to a clinician about tirzepatide or semaglutide options today rather than waiting on an unapproved drug.
FAQ
Is retatrutide better than Zepbound for weight loss?
In trials, retatrutide produced more weight loss (up to about 24% in phase 2 and 28% in phase 3) than Zepbound's roughly 21% in SURMOUNT-1. But these are separate trials, not a head-to-head comparison, and retatrutide is not yet approved, so "better" is based on early data, not real-world use.
Is retatrutide FDA-approved?
No. As of 2026 retatrutide is investigational and in phase 3 trials. It is not approved by the FDA or any other major regulator. Zepbound, by contrast, has been FDA-approved since November 2023.
What is the difference between retatrutide and tirzepatide?
Tirzepatide (the drug in Zepbound) is a dual agonist that targets GLP-1 and GIP. Retatrutide is a triple agonist that targets GLP-1, GIP, and the glucagon receptor. The added glucagon activity is thought to drive extra weight loss by increasing energy expenditure.
Can I switch from Zepbound to retatrutide?
Not through legitimate channels, because retatrutide is not commercially available. If retatrutide is approved in the future, switching would be a clinical decision to make with your prescriber based on results, tolerance, and cost.
Do retatrutide and Zepbound have the same side effects?
They share the same dominant gastrointestinal side effects (nausea, diarrhea, vomiting, constipation), since both act on GLP-1 and GIP. Retatrutide's glucagon activity adds dose-related increases in heart rate and some glucose changes seen in trials, which are still being studied.
This article is for informational purposes only and is not medical advice. Talk to a qualified clinician before starting, stopping, or changing any medication.
Sources
- Jastreboff AM, et al. "Triple-Hormone-Receptor Agonist Retatrutide for Obesity, A Phase 2 Trial." New England Journal of Medicine, 2023.
- Eli Lilly. "Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial" (TRIUMPH-1), December 2025.
- Eli Lilly / FDA. "FDA Approves Lilly's Zepbound (tirzepatide) for Chronic Weight Management" and SURMOUNT-1 results.
