Retatrutide vs tirzepatide: what the trials show, and what you can get today

Tirzepatide is a dual agonist: it activates the GLP-1 receptor and the GIP receptor. It is approved in the United States as Mounjaro for type 2 diabetes and as Zepbound for weight management, both under Eli Lilly applications on the FDA's register ^[8]. Our tirzepatide page covers the mechanism and the approval history.

Retatrutide adds a third: it agonises the glucagon receptor as well, which is where the extra energy expenditure is thought to come from. It is made by the same company. It is approved nowhere — not by the FDA, not by the EMA, not by the MHRA. The FDA's register of approved applications returns nothing for it, which is exactly what an unapproved molecule should return ^[8]. Our retatrutide page goes through the mechanism in full.

That asymmetry is the whole comparison, and the rest of this page is about how to think about it without pretending it away.

SURMOUNT-1 ^[1] is the Phase 3 obesity trial: 2,539 adults with a BMI of 30 or more, or 27 or more with a weight-related complication, excluding diabetes, randomised to tirzepatide 5 mg, 10 mg, 15 mg or placebo for 72 weeks.

Mean weight change at week 72 was −15.0% at 5 mg, −19.5% at 10 mg and −20.9% at 15 mg, against −3.1% on placebo. A fifth or more of body weight was lost by 50% of the 10 mg group and 57% of the 15 mg group, against 3% on placebo. Adverse events caused discontinuation in 4.3%, 7.1% and 6.2% across the three doses, against 2.6% on placebo.

Retatrutide's Phase 2 trial ^[2] reported −24.2% at 48 weeks on 12 mg, and that is the figure much of the internet still quotes. It has been superseded twice: first by company toplines, then by peer-reviewed papers.

TRIUMPH-1 was published in the New England Journal of Medicine on 29 September 2026 ^[10]: 2,339 adults with obesity and without diabetes, randomised to 4 mg, 9 mg, 12 mg or placebo for 80 weeks. Counting everyone randomised (the treatment-regimen estimand), mean weight change was −17.6% at 4 mg, −23.7% at 9 mg and −25.0% at 12 mg, against −3.9% on placebo — differences from placebo of 19.8 and 21.0 percentage points at the two higher doses. The trial also met its other primary endpoints: knee-osteoarthritis pain fell further than on placebo in the 574 participants with that condition, and sleep-apnoea events per hour fell further in the 243 with obstructive sleep apnoea.

Lilly's May press release had reported −19.0%, −25.9% and −28.3% against −2.2% ^[3]. Those are efficacy-estimand figures: they estimate the result had everyone stayed on treatment, so they run higher. The same release reported that, on that basis, 45.3% of the 12 mg group lost 30% or more of their weight, and that a pre-specified extension to 104 weeks in 532 participants with a BMI of 35 or above averaged 30.3% on 12 mg.

TRIUMPH-2, in 1,152 adults with obesity and type 2 diabetes, was published in The Lancet the same day ^[11]: −11.9%, −16.8% and −18.8% at 80 weeks across the three doses, against −5.1% on placebo, on the treatment-regimen estimand. TRIUMPH-3, in 1,949 adults with severe obesity and cardiovascular disease, has so far been reported only in Lilly's July press release ^[4]: −21.6% at 9 mg and −22.6% at 12 mg over 80 weeks.

These are the largest weight reductions any obesity pharmacotherapy has reported in Phase 3.

Put the headline figures next to each other — −28.3% against −20.9% — and the gap looks like seven and a half percentage points. Most of that gap is how the numbers were counted, and it is worth being precise about it rather than waving at "different trials".

The −28.3% in Lilly's press release is an efficacy-estimand figure; SURMOUNT-1's −20.9% is a treatment-regimen figure. Put both trials on the treatment-regimen basis and subtract placebo, and the gap is about three percentage points (21.0 against 17.8), not seven and a half. Retatrutide's own trial still shows more weight loss, and it ran eight weeks longer on a curve that was still descending.

What the table cannot fix is that these are two trials, run years apart, in different people. Both are now peer-reviewed, so the figures are no longer press-release numbers. They are still not a head-to-head comparison.

None of the above is how this question gets settled, and it does not have to stay unsettled.

Eli Lilly is running TRIUMPH-5 (NCT06662383) ^[5], a Phase 3 trial of retatrutide compared to tirzepatide in adults with obesity. It has 800 participants, it is no longer recruiting, and its estimated primary completion date is November 2026 (registry read 19 October 2026). Results come later, when Lilly reports them.

That is the trial that answers the question this page is about. A second one, TRANSCEND-T2D-2 (NCT06260722) ^[6], compared retatrutide with semaglutide in type 2 diabetes. Lilly reported its topline results on 28 October 2026: both retatrutide doses lowered A1C more than Ozempic 2 mg and produced more than twice the weight loss over 80 weeks (what the trial showed). It answers the question against semaglutide, not against tirzepatide.

Anyone making a decision on the cross-trial arithmetic in section 4 is making it shortly before the real answer arrives.

The efficacy comparison is the one that gets quoted. The tolerability comparison runs the other way.

Discontinuation because of adverse events in TRIUMPH-1 was 4.1% at 4 mg, 6.9% at 9 mg and 11.3% at 12 mg, against 4.9% on placebo, as reported in Lilly's May press release ^[3]. In TRIUMPH-3, at the top two doses, it was 9.8% and 13.5% against 4.8% ^[4]. In the published TRIUMPH-2 paper, permanent discontinuation because of adverse events or death was 4% at 4 mg, 12% at 9 mg and 8% at 12 mg, against 5% on placebo ^[11]. In SURMOUNT-1, tirzepatide's was 4.3% to 7.1% across its three doses.

So roughly one in nine people left the retatrutide 12 mg arm over side effects, and in the cardiovascular-disease population roughly one in seven. That is the dose the headline weight-loss figure belongs to.

There is also a finding that has no counterpart in the tirzepatide programme. Lilly's TRIUMPH-1 release reported dysesthesia — altered or unpleasant skin sensation — in 5.1% to 12.5% of participants across doses, against 0.9% on placebo ^[3]; the TRIUMPH-2 paper found it in 4% to 7% against 1%, along with more hypotension (1% to 6% against under 1%) ^[11]. It is dose-related, it is new to this class, and what it means over years is not yet known. A drug that has been prescribed to millions of people since 2022 has a different quantity of safety information behind it than one whose first Phase 3 papers appeared in September 2026, independent of what either drug does to weight.

As of 19 October 2026:

Retatrutide has no application before the FDA. Lilly's latest stated timeline, from 23 July 2026, is that it plans to submit a Biologics License Application in the first quarter of 2027 ^[4]. A plan to file is not a filing. After a filing comes a review that typically runs several months to a year.

It is on no shortage list, and cannot be. Shortage listings apply to approved drugs. That is why no compounding pathway covers retatrutide: 503A and 503B authorise compounding of drugs that exist in an approved form, and the FDA separately proposed in April 2026 to exclude the approved GLP-1 molecules from the 503B bulks list altogether ^[9].

Tirzepatide, by contrast, is on the register under Lilly's applications for both Mounjaro and Zepbound ^[8], with every strength and presentation listed.

Three things get called availability and only one of them is a prescription.

Clinical trials. Several TRIUMPH studies have completed; others are active and not recruiting; the cardiovascular and kidney outcomes trial, with 10,000 participants, does not reach primary completion until February 2029.

Expanded access. Lilly has a pre-approval expanded access record for retatrutide on ClinicalTrials.gov, NCT07629401 ^[7], listed as available. Expanded access is a real FDA pathway for patients outside a trial, arranged through a treating physician. We have not read its eligibility criteria and do not summarise who qualifies; that is on the record itself, and a clinician is the one who applies.

Everything else. The vials sold as "research use only", the peptide vendors, the telehealth sites offering it — none of that sits inside any FDA-recognised framework, because there is no approved product for it to be a version of. The practical problem is not only legal: there is no verified potency, no sterility assurance and no identity guarantee a buyer in that market can rely on. What to ask before your first order is about sellers of approved and compounded drugs, and every question in it fails immediately here.

If the file runs as Lilly plans — filing in Q1 2027, a standard review — a first approval lands somewhere in late 2027 or 2028, and those are projections rather than commitments. Call it eighteen months to two and a half years from today, with the usual possibility that it slips.

Set against that: tirzepatide at 15 mg produced a mean 20.9% over 72 weeks in Phase 3, and 57% of that group lost a fifth or more of their body weight. Someone who starts now is, on the trial evidence, most of the way through that by the time retatrutide reaches a pharmacy.

The other half of the arithmetic is that GLP-1 weight loss is maintenance therapy rather than a course. Stopping brings most of it back — the STEP 1 extension found about two-thirds regained within a year of withdrawal. So "start tirzepatide now and switch later" is a coherent plan in a way that "wait, and start nothing" is not.

If you are deciding between them today, you are not. One is prescribable and one is not obtainable outside a trial or expanded access. That is the decision, and it is already made.

If retatrutide is genuinely the drug you want, the legitimate routes are trial enrolment while studies recruit, and expanded access through a treating physician. Both run through a clinician, and neither runs through a website.

If you want the best available treatment now, tirzepatide is the most effective approved obesity drug on head-to-head evidence — it beat semaglutide in SURMOUNT-5, which is a real head-to-head rather than a cross-trial one.

If you are watching the file, the date to watch is not the approval. It is the TRIUMPH-5 head-to-head readout, after its primary completion in November 2026, and the TRIUMPH-3 paper. TRIUMPH-1 and TRIUMPH-2 are already published.

This page is informational and is not medical advice. It compares published trial results and regulatory records; it cannot tell you what is appropriate for you. Tirzepatide carries a boxed warning for thyroid C-cell tumours and is contraindicated in people with a personal or family history of medullary thyroid carcinoma or MEN 2. Retatrutide is investigational: its full safety profile is not established, and nothing on this page should be read as encouragement to obtain it outside a clinical trial or an authorised expanded access programme. Figures from company press releases are labelled as such and are not peer-reviewed; TRIUMPH-1 and TRIUMPH-2 figures cite the published papers. Every figure carries the date it was read.