Retatrutide vs Tirzepatide: What the Phase 3 Trials Show in 2026
Retatrutide (LY3437943) is Eli Lilly's once-weekly agonist of the GIP, GLP-1 and glucagon receptors. Tirzepatide, also from Lilly, acts on GIP and GLP-1 only and is already sold as Mounjaro and Zepbound. Since this page first went up in July, retatrutide has gone from one phase 2 paper to five phase 3 readouts, and the two biggest are now peer reviewed: TRIUMPH-1 in the New England Journal of Medicine and TRIUMPH-2 in The Lancet, both published online on 29 September 2026. For the molecule on its own, with the phase 3 results and where it stands with the FDA, see the retatrutide guide.
Every number below comes from those papers, Lilly's own trial releases, FDA records or the ClinicalTrials.gov registry, and each one is linked. This is a research reference, not medical advice. If you are prescribed Mounjaro or Zepbound, your prescriber's plan comes first.
Retatrutide vs tirzepatide at a glance
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Check price at Amino Club Compare all vendors| What | Retatrutide | Tirzepatide |
|---|---|---|
| Mechanism | GIP, GLP-1 and glucagon receptor agonist (NEJM 2026) | GIP and GLP-1 receptor agonist (NEJM 2022) |
| Pivotal obesity trial | TRIUMPH-1, phase 3: 2,339 adults with obesity, no diabetes, 80 weeks (NEJM 2026) | SURMOUNT-1, phase 3: 2,539 adults with obesity, or overweight plus a weight-related complication, no diabetes, 72 weeks (NEJM 2022) |
| Top dose studied | 12 mg once weekly (TRIUMPH-1) | 15 mg once weekly (SURMOUNT-1) |
| Mean weight loss, treatment-regimen estimand (all randomised participants, whether or not they stayed on drug) | 25.0% at week 80 on 12 mg vs 3.9% on placebo (NEJM 2026) | 20.9% at week 72 on 15 mg vs 3.1% on placebo (NEJM 2022) |
| Mean weight loss, efficacy estimand (as if everyone stayed on drug) | 28.3% at week 80 on 12 mg vs 2.2% on placebo (Lilly, May 2026) | 22.5% at week 72 on 15 mg vs 2.4% on placebo (Lilly, April 2022) |
| Stopped because of adverse events, top dose vs placebo | 11.3% vs 4.9% (TRIUMPH-1, Lilly, May 2026) | 6.2% vs 2.6% (SURMOUNT-1, NEJM 2022) |
| Other key trial | Phase 2: 24.2% at week 48 on 12 mg vs 2.1% on placebo, 338 adults (NEJM 2023) | SURMOUNT-5: 20.2% vs 13.7% with semaglutide at week 72, head to head (NEJM 2025) |
| FDA status | Not approved. Investigational; Lilly plans to submit a Biologics License Application in the first quarter of 2027 (Lilly, July 2026) | Approved: Mounjaro on 13 May 2022 (Drugs@FDA), Zepbound on 8 November 2023 (Drugs@FDA) |
| Brand names | None yet | Mounjaro for type 2 diabetes (label); Zepbound for weight reduction and obstructive sleep apnoea in adults with obesity (label) |
| Dosing frequency | Once-weekly injection under the skin in every trial (NEJM 2026) | Once-weekly injection under the skin (Zepbound label) |
These are separate trials, not a head-to-head comparison. TRIUMPH-1 ran eight weeks longer and its participants started heavier (mean 112.7 kg, BMI 40.0, per Lilly) than SURMOUNT-1's (mean 104.8 kg, BMI 38.0, per NEJM 2022). A direct trial, TRIUMPH-5, is running but has not reported (details below).
Mechanism: what the extra receptor adds
Tirzepatide activates two receptors, GIP and GLP-1 (SURMOUNT-1). Retatrutide activates the same two plus the glucagon receptor (TRIUMPH-1). Both are given once a week by injection under the skin, and both come from Eli Lilly.
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Build your stack, 2 minutesThe glucagon receptor is the whole difference between the two molecules, and the trials show what comes with it in practice: more weight loss at the top dose, and a few effects tirzepatide's label does not list. In the phase 2 trial, retatrutide raised heart rate in a dose-dependent way, with the increase peaking at 24 weeks and declining after that (NEJM 2023). In phase 3, dysesthesia (an altered or unpleasant skin sensation) appeared far more often on retatrutide than on placebo (see side effects below).
What none of the published trials measure is how much of the extra weight loss comes from the glucagon arm itself. That is a working hypothesis, not a result. Mazdutide, a GLP-1 and glucagon dual agonist, is the other glucagon-containing compound we track.
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Every retatrutide readout so far
Lilly has reported five phase 3 retatrutide trials since December 2025, on top of the 2023 phase 2 paper. Here they are in order, with the top-dose result and the estimand each source used. Placebo figures are from the same trial.
| Trial and readout | Who and how long | Top-dose weight loss vs placebo | Stopped for adverse events, top dose vs placebo | Source |
|---|---|---|---|---|
| Phase 2 (June 2023) | 338 adults with obesity or overweight, 48 weeks | 24.2% vs 2.1% on 12 mg (least-squares mean) | Not given in the abstract | NEJM 2023 |
| TRIUMPH-4 (topline 11 December 2025) | 445 adults with obesity or overweight and knee osteoarthritis, no diabetes, 68 weeks | 28.7% vs 2.1% on 12 mg (efficacy); 23.7% vs 4.6% (treatment-regimen) | 18.2% vs 4.0% | Lilly, December 2025 |
| TRANSCEND-T2D-1 (ADA 2026) | Adults with type 2 diabetes on diet and exercise alone, 40 weeks | Up to 16.8% weight loss and up to 1.9 points off HbA1c | 2% to 5% across doses | Lilly ADA 2026 presentation |
| TRIUMPH-1 (topline 21 May 2026; NEJM 29 September 2026) | 2,339 adults with obesity, no diabetes, 80 weeks | 28.3% vs 2.2% on 12 mg (efficacy); 25.0% vs 3.9% (treatment-regimen) | 11.3% vs 4.9% | NEJM 2026, Lilly, May 2026 |
| TRIUMPH-2 (topline 23 July 2026; Lancet 29 September 2026) | 1,152 adults with obesity or overweight and type 2 diabetes, 80 weeks | 20.8% vs 4.0% on 12 mg (efficacy); 18.8% vs 5.1% (treatment-regimen) | 7.7% vs 4.9% | Lancet 2026, Lilly, July 2026 |
| TRIUMPH-3 (topline 23 July 2026) | 1,949 adults with a BMI of 35 or more and established cardiovascular disease, 80 weeks | 22.6% vs 3.2% on 12 mg (efficacy) | 13.5% vs 4.8% | Lilly, July 2026 |
Three details matter beyond the headline numbers. First, in a pre-specified extension of TRIUMPH-1 to 104 weeks, 532 participants with a starting BMI of 35 or more reached a mean loss of 30.3% in the 12 mg group (efficacy estimand), according to Lilly. Second, the NEJM paper reports that TRIUMPH-1 also reduced knee pain in 574 participants with knee osteoarthritis and reduced breathing events in 243 participants with obstructive sleep apnoea (NEJM 2026). Third, TRIUMPH-3 counted 44 major cardiovascular events (MACE-5) on retatrutide against 52 on placebo, a hazard ratio of 0.82 with a 95% confidence interval of 0.55 to 1.22 (Lilly, July 2026). That interval crosses 1, so it shows no proven cardiovascular benefit either way. The dedicated outcomes trial, TRIUMPH-Outcomes, lists an estimated primary completion of February 2029 (NCT06383390).
Weight loss: reading the numbers honestly
Trials of these drugs report two kinds of average. The treatment-regimen estimand counts everyone who was randomised, including people who stopped the drug. The efficacy estimand estimates what would have happened had everyone stayed on treatment, so it always looks better. A fair comparison uses the same estimand on both sides:
- Treatment-regimen: retatrutide 12 mg, 25.0% at week 80 (TRIUMPH-1), against tirzepatide 15 mg, 20.9% at week 72 (SURMOUNT-1). A gap of about 4 percentage points.
- Efficacy: retatrutide 12 mg, 28.3% at week 80 (Lilly), against tirzepatide 15 mg, 22.5% at week 72 (Lilly). A gap of about 6 percentage points.
Even like for like, these are indirect comparisons. TRIUMPH-1 ran eight weeks longer, started from a heavier group and used different doses and escalation. The older comparison many sites still quote, 24.2% at 48 weeks for retatrutide against 20.9% at 72 weeks for tirzepatide, mixes a 338-person phase 2 trial with a 2,539-person phase 3 trial and should be retired now that phase 3 data exist.
The trial that will settle it is TRIUMPH-5 (NCT06662383): a phase 3, randomised, double-blind study of retatrutide against tirzepatide in adults with obesity, an estimated 800 participants, with percent change in body weight at week 80 as the primary endpoint. The registry lists it as active, not recruiting, with primary completion estimated for November 2026. No results had been released as of 14 October 2026.
Side effects: where the profiles differ
Both drugs mainly cause gastrointestinal side effects, and on the numbers available retatrutide's top dose produces more of them. The table sets TRIUMPH-1 against the Zepbound label, which pools SURMOUNT-1 with a second 72-week weight trial. Different trials again, so read the gap as indicative.
| Side effect | Retatrutide 12 mg (TRIUMPH-1) | Placebo (TRIUMPH-1) | Tirzepatide 15 mg (Zepbound label) | Placebo (Zepbound label) |
|---|---|---|---|---|
| Nausea | 42.4% | 14.8% | 28% | 8% |
| Vomiting | 25.3% | 4.8% | 13% | 2% |
| Diarrhoea | 32.0% | 13.5% | 23% | 8% |
| Constipation | 26.1% | 10.9% | 11% | 5% |
| Dysesthesia | 12.5% | 0.9% | Not in the label's common adverse reaction table | Not listed |
| Stopped for adverse events | 11.3% | 4.9% | 6.7% | 3.4% |
| Source | Lilly, May 2026 | Zepbound prescribing information | ||
Dysesthesia is the retatrutide-specific signal to watch. It ran at 12.5% on 12 mg in TRIUMPH-1 and 20.9% on 12 mg in TRIUMPH-4, against under 1% on placebo; Lilly says the events were generally mild to moderate and most resolved during treatment (TRIUMPH-1, TRIUMPH-4). In TRIUMPH-2, hypotension was also more frequent on retatrutide (6% on 12 mg vs under 1% on placebo, Lancet 2026).
Tirzepatide carries a boxed warning: it causes thyroid C-cell tumours in rats, it is unknown whether it does in humans, and it is contraindicated in people with a personal or family history of medullary thyroid carcinoma or MEN 2 (Zepbound label). Retatrutide has no label yet. For the full pictures, see retatrutide side effects and tirzepatide side effects.
Doses the trials used
Retatrutide has no approved dose; the figures below are what the trials used, reported for reference only and not as a protocol. For the full schedules see the retatrutide dosage guide and the tirzepatide dosage guide.
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Open the retatrutide or tirzepatide calculator peptulator.com, the Bureau's independent tool| Study | Start | Escalation | Doses studied | Source |
|---|---|---|---|---|
| Retatrutide phase 2 | 2 mg or 4 mg weekly, depending on arm | Stepped up to the assigned dose | 1, 4, 8 or 12 mg weekly for 48 weeks | NEJM 2023 |
| Retatrutide, TRIUMPH-1 | 2 mg weekly | Every four weeks to the target dose | 4, 9 or 12 mg weekly for 80 weeks | Lilly, May 2026 |
| Tirzepatide, SURMOUNT-1 | Not stated in the abstract | 20-week dose-escalation period | 5, 10 or 15 mg weekly for 72 weeks | NEJM 2022 |
| Tirzepatide, Zepbound label | 2.5 mg weekly for 4 weeks, then 5 mg | Up in 2.5 mg steps after at least 4 weeks on the current dose | Maintenance 5, 10 or 15 mg weekly; maximum 15 mg | Zepbound label |
TRIUMPH-1 and the Zepbound label both escalate in four-week steps. The tirzepatide label says the escalation schedule is there to reduce the risk of gastrointestinal adverse reactions (Mounjaro label).
Approval status and availability in 2026
Tirzepatide. Drugs@FDA lists Mounjaro (NDA 215866) as approved on 13 May 2022 and Zepbound (NDA 217806) on 8 November 2023 (Mounjaro, Zepbound). The FDA's Zepbound announcement covered chronic weight management; the current Zepbound label covers weight reduction and moderate to severe obstructive sleep apnoea in adults with obesity. The current Mounjaro label covers glycaemic control in type 2 diabetes from age 10, plus reducing the risk of major cardiovascular events in adults with type 2 diabetes at high risk (Mounjaro label). Pricing is on our tirzepatide cost page.
Retatrutide. Not FDA approved. Lilly's 23 July 2026 release says it is completing the chemistry, manufacturing and controls package and plans to submit a Biologics License Application to the FDA in the first quarter of 2027 (Lilly, July 2026). Lilly states that retatrutide is legally available only to participants in its clinical trials (Lilly, May 2026). ClinicalTrials.gov also lists a pre-approval, single-patient expanded access programme for adults with a BMI of 35 or more and at least two serious obesity-related complications who have not responded to the best approved therapy and cannot join a trial (NCT07629401). See also retatrutide cost.
Research-grade material. Peptide vendors sell both compounds for laboratory research only, not for human use. The rules differ by country and are tightening; our research peptides legal status guide and peptide enforcement tracker cover where things stand. If you compare suppliers, third-party COA testing is the first thing to check, and the vendor scorecard covers it.
Vendor recommendations for GLP-1 peptides
Pantheon and Amino Club both carry tirzepatide and retatrutide with third-party COA verification. We've reviewed their testing practices and purity records.
Pantheon Peptides Amino ClubWhich has the stronger case?
Tirzepatide has the deeper evidence base: two FDA-approved brands, a label that now includes obstructive sleep apnoea and, on Mounjaro, cardiovascular risk reduction in type 2 diabetes, and a phase 3 head-to-head win over semaglutide (SURMOUNT-5).
Retatrutide has produced the larger mean weight loss in its own trials, under both estimands and across five phase 3 readouts. The trade-offs on the current data: more people stopped for adverse events at 12 mg (11.3% in TRIUMPH-1, 18.2% in TRIUMPH-4), a dysesthesia signal tirzepatide's label does not show, no approved label, and no completed cardiovascular outcomes trial.
Bottom line
On weight loss alone, retatrutide leads by roughly 4 to 6 percentage points when you compare the pivotal trials on the same estimand, but that is an indirect comparison and TRIUMPH-5 has not reported. Tirzepatide is the approved, better-characterised option today. Retatrutide remains investigational, and Lilly plans to file it with the FDA in the first quarter of 2027.
How both compare with semaglutide
Tirzepatide has already been tested directly against semaglutide. In SURMOUNT-5, an open-label phase 3b trial in 751 adults with obesity and no diabetes, tirzepatide at the maximum tolerated dose cut weight by 20.2% at week 72 against 13.7% with semaglutide (NEJM 2025). Retatrutide's comparison with semaglutide, TRANSCEND-T2D-2 in type 2 diabetes, is registered as an open-label phase 3 trial with a primary completion date of 27 August 2026 (NCT06260722); we found no published results as of 14 October 2026.
More on that side of the family: semaglutide vs tirzepatide and retatrutide vs Ozempic.
Frequently Asked Questions
Is retatrutide stronger than tirzepatide?
On weight loss in separate trials, yes. Retatrutide 12 mg cut body weight by 25.0% at week 80 in TRIUMPH-1, against 20.9% at week 72 for tirzepatide 15 mg in SURMOUNT-1, both by the treatment-regimen estimand. The trials differed in length and population, and the direct comparison, TRIUMPH-5, has not reported yet.
What is the difference between retatrutide and tirzepatide?
Tirzepatide activates two receptors, GIP and GLP-1, and is FDA approved as Mounjaro and Zepbound. Retatrutide activates three, GIP, GLP-1 and glucagon, and is still investigational. Both are once-weekly injections made by Eli Lilly.
Is retatrutide FDA approved?
No. As of 14 October 2026 retatrutide is investigational. Lilly said in July 2026 that it plans to submit a Biologics License Application to the FDA in the first quarter of 2027, and it states that retatrutide is legally available only to participants in its clinical trials.
When will retatrutide be available?
Lilly has not given a launch date. Its stated plan is to file with the FDA in the first quarter of 2027, and approval could only follow an FDA review. Until then the legal routes are Lilly's clinical trials and a single-patient expanded access programme for adults with severe obesity and serious complications.
Does retatrutide have more side effects than tirzepatide?
At the top doses, the trial numbers point that way. In TRIUMPH-1, 42.4% on retatrutide 12 mg reported nausea against 14.8% on placebo, and 11.3% stopped for adverse events. On the Zepbound label, nausea was 28% on tirzepatide 15 mg against 8% on placebo, and 6.7% stopped. Retatrutide also showed dysesthesia, an altered skin sensation. These are different trials, so the gap is indicative.
Can you switch from tirzepatide to retatrutide?
Not through any approved route, because retatrutide is not approved. We found no published trial that tested a switch. The head-to-head TRIUMPH-5 trial excluded people who had taken weight-loss drugs in the 90 days before screening, so it will not answer that question either.
Is there a head-to-head trial of retatrutide vs tirzepatide?
Yes, one is running. TRIUMPH-5 (NCT06662383) is a phase 3, double-blind trial randomising an estimated 800 adults with obesity to retatrutide or tirzepatide, with percent weight change at week 80 as the primary endpoint. The registry lists primary completion in November 2026, and no results had been released by 14 October 2026.
Sources
- Jastreboff et al, Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity (TRIUMPH-1), New England Journal of Medicine, 2026
- Bellido et al, Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2), The Lancet, 2026
- Jastreboff et al, Triple-Hormone-Receptor Agonist Retatrutide for Obesity, A Phase 2 Trial, New England Journal of Medicine, 2023
- Jastreboff et al, Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1), New England Journal of Medicine, 2022
- Aronne et al, Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5), New England Journal of Medicine, 2025
- Lilly, retatrutide delivered powerful weight loss in pivotal Phase 3 obesity trial (TRIUMPH-1 topline), press release via BioSpace, May 2026
- Lilly, retatrutide successful in two additional Phase 3 obesity trials (TRIUMPH-2 and TRIUMPH-3), press release via PR Newswire, July 2026
- Lilly, retatrutide weight loss and osteoarthritis pain relief in first Phase 3 trial (TRIUMPH-4), press release via BioSpace, December 2025
- Lilly, results of the first Phase 3 study of retatrutide in type 2 diabetes (TRANSCEND-T2D-1), ADA Scientific Sessions, 2026
- Lilly, SURMOUNT-1 topline results, tirzepatide up to 22.5% weight loss, via Bariatric News, 2022
- TRIUMPH-5, retatrutide compared to tirzepatide in adults who have obesity, ClinicalTrials.gov NCT06662383, 2026
- Pre-approval expanded access of retatrutide, ClinicalTrials.gov NCT07629401, 2026
- TRANSCEND-T2D-2, retatrutide compared with semaglutide in type 2 diabetes, ClinicalTrials.gov NCT06260722, 2026
- TRIUMPH-Outcomes, retatrutide cardiovascular and kidney outcomes, ClinicalTrials.gov NCT06383390, 2026
- FDA approves new medication for chronic weight management (Zepbound), FDA, 2023
- Drugs@FDA, Mounjaro NDA 215866, FDA
- Drugs@FDA, Zepbound NDA 217806, FDA
- Zepbound prescribing information, DailyMed, 2026
- Mounjaro prescribing information, DailyMed, 2026
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