On published trials retatrutide has produced more weight loss than tirzepatide — 24.2% against 20.9%. Those are separate studies, so it is an estimate rather than a result. But unusually for this kind of comparison, the real answer is already being generated: a phase 3 trial putting the two drugs head to head in 800 adults is enrolled and running. The other difference matters more today. Zepbound is approved and available; retatrutide is not.
Side by side
| Retatrutide | Zepbound | |
|---|---|---|
| Status | Investigational, phase 3 | FDA approved |
| Targets | GLP-1, GIP, glucagon | GLP-1, GIP |
| Weight loss, obesity | 24.2% at 48 wks (phase 2, n=338) | 20.9% at 72 wks (n=2,539) |
| Weight loss, type 2 diabetes | 15.3% at 40 wks (phase 3, n=537) | ~14.7% at 72 wks |
| Stopped for side effects | 2–5% | ~10% |
| Can you get it | No | Yes, by prescription |
| Also approved for | — | Obstructive sleep apnoea |
| Maker | Eli Lilly — both | |
Both drugs belong to the same company, which is running a trial of its investigational molecule against its own approved one.
The comparison that actually controls for something
The headline pairing — 24.2% against 20.9% — compares a 338-person phase 2 trial over 48 weeks with a 2,539-person phase 3 over 72. Different sizes, different durations, three years apart. It is the comparison everyone makes and it is the weaker one.
There is a tighter reading available. Both drugs have now been tested in adults with type 2 diabetes, a population where every drug in this class loses less weight:
| In type 2 diabetes | Weight loss | Duration | Phase |
|---|---|---|---|
| Retatrutide 12 mg | 15.3% | 40 weeks | 3 |
| Tirzepatide 15 mg | ~14.7% | 72 weeks | 3 |
Same patient type, both phase 3, and retatrutide reached a slightly higher figure in nearly half the time. Still not a head-to-head, but far closer to like-for-like than the headline pairing, and it points the same direction.
The trial that will settle it
NCT06662383 is a phase 3 study of retatrutide compared with tirzepatide in 800 adults with obesity. It is enrolled and running, and has not reported.
This is worth knowing for a specific reason: the last time this question came up in this drug class, cross-trial estimates turned out to be roughly right but not precisely right. SURMOUNT-5 compared tirzepatide with semaglutide directly and found 20.2% against 13.7% — the ordering everyone expected, at figures neither of the separate trials would have predicted exactly.
So the reasonable position on retatrutide versus tirzepatide is that retatrutide is probably ahead, by an amount nobody can currently state. Anyone giving you a precise margin is giving you arithmetic, not evidence.
Tolerability, where the gap may be wider than the efficacy gap
In its phase 3 trial, 2 to 5% of retatrutide patients discontinued for adverse events, against 0% on placebo. Zepbound's trial with a lifestyle lead-in reported about 10%.
Different trials, different lengths, different populations — so treat it as a signal rather than a measurement. But it is a large gap in the direction that matters, and it fits a pattern already established in this class: when tirzepatide and semaglutide were compared directly, the stronger drug was also the better tolerated one. If that holds again, retatrutide may be both more effective and easier to take.
The caution is scale. Zepbound's figure comes from thousands of patients across a full programme; retatrutide's comes from 537 people over 40 weeks. Rare and late-emerging problems are exactly what small trials cannot see, and phase 2 also recorded dose-dependent heart rate increases peaking at 24 weeks. Details in retatrutide side effects.
What Zepbound has that no trial result can offset
You can actually take it. Zepbound has an FDA label, a known dose, a pharmacy that dispenses it, a manufacturer accountable for what is in the vial, and years of post-marketing surveillance. Retatrutide has none of these.
That is not a technicality about paperwork. Three products sold online as retatrutide were analysed in Australia in 2026 and contained 51%, 165% and 190% of their labelled dose. A drug that beats Zepbound in a trial does not beat it in a vial of unknown strength.
And a second indication. Zepbound is approved for moderate-to-severe obstructive sleep apnoea in adults with obesity, which can open a route to insurance coverage that weight alone does not.
What this means in practice
- If you are choosing a treatment today: the comparison is between an approved drug and nothing. Zepbound, or one of the other approved options in the best GLP-1 for weight loss.
- If you are asking which is the better molecule: the evidence leans retatrutide, on both efficacy and tolerability, and the head-to-head has not reported.
- If you are considering buying retatrutide online: the dose in the vial is unknown, which makes every number on this page inapplicable. See can you buy retatrutide.
- If you want to know when it might change: retatrutide's phase 3 programme runs to fourteen trials, tracked in the GLP-1 pipeline tracker.
Scientific References
4 sources- 1
Jastreboff AM, Kaplan LM, Frías JP, et al.
Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial
New England Journal of Medicine · 389(6) · 2023PMID: 37366315
NEJM - 2
Bajaj HS, Welch M, Shah P, et al.
Efficacy and safety of retatrutide in people with type 2 diabetes (TRANSCEND-T2D-1): a phase 3 trial
The Lancet · 407(10546) · 2026PMID: 42250575
- 3
Jastreboff AM, Aronne LJ, Ahmad NN, et al.
Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1)
New England Journal of Medicine · 387(3) · 2022PMID: 35658024
NEJM - 4
U.S. National Library of Medicine
NCT06662383 — A Study of Retatrutide (LY3437943) Compared to Tirzepatide in Participants With Obesity, phase 3, 800 participants; status read 13 August 2026
ClinicalTrials.gov · 2026
References open in a new tab. Content is reviewed against peer-reviewed literature as part of our editorial policy.
About the author
Editor, Modern Weight Science
Claudiu Gheorghe is the editor of Modern Weight Science. He is not a physician. His role is to synthesize peer-reviewed studies, clinical-trial data, and FDA prescribing information into clear, plain-language explanations, and to make sure every factual claim on the site traces back to a cited source. Any decision about starting, changing, or stopping a medication belongs with a licensed clinician who knows your history.
Every claim is checked against peer-reviewed research through our review process and fact-checking policy.
Frequently Asked Questions
Is retatrutide better than Zepbound?
The published evidence leans that way and no head-to-head has reported. Retatrutide reached 24.2% mean weight loss in phase 2 against tirzepatide's 20.9% in SURMOUNT-1, and in type 2 diabetes — a much closer comparison, both phase 3 — it reached 15.3% in 40 weeks against roughly 14.7% over 72. A direct trial in 800 adults, NCT06662383, is running and has not reported.
When will we know if retatrutide beats Zepbound?
When NCT06662383 reports. It is a phase 3 study comparing the two drugs directly in 800 adults with obesity, enrolled and running. The precedent is SURMOUNT-5, which compared tirzepatide with semaglutide and confirmed the expected ordering at figures neither separate trial would have predicted exactly — so expect the direction to hold and the margin to surprise.
Which has fewer side effects, retatrutide or Zepbound?
On the available figures, retatrutide: 2 to 5% discontinued for adverse events in its phase 3 trial against 0% on placebo, where Zepbound reported around 10% in the trial with a lifestyle lead-in. Those come from trials of very different sizes and lengths, so treat it as a signal. Retatrutide's data covers 537 people over 40 weeks and cannot show what is rare.
Can I take retatrutide instead of Zepbound?
Not as a prescribed medicine. Retatrutide is not approved anywhere, so no clinician can prescribe it and no pharmacy can dispense it, apart from a narrow compassionate use programme. Zepbound is approved, has a known dose and a manufacturer accountable for the contents of the vial. Products sold online as retatrutide have been measured at 51% to 190% of their labelled dose.
Are retatrutide and Zepbound made by the same company?
Yes, both are Eli Lilly. Zepbound is tirzepatide, approved, activating GLP-1 and GIP. Retatrutide is investigational and adds a third target, glucagon. Lilly is running a phase 3 trial of its investigational drug against its own approved one.
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Where to read next
Not medical advice. This guide is for general education only. GLP-1 medications, dosing, and treatment suitability are decisions for you and a licensed clinician who knows your full medical history.