Comparisons
Retatrutide vs tirzepatide: trial weight loss, dosing and status
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Short answer
Tirzepatide (Zepbound, Mounjaro) is an FDA-approved GIP and GLP-1 receptor agonist. Retatrutide adds glucagon receptor activity and is not approved anywhere as of Oct 19, 2026. On the treatment-regimen estimand, retatrutide 12 mg averaged −25.0% at 80 weeks (TRIUMPH-1) and tirzepatide 15 mg −20.9% at 72 weeks (SURMOUNT-1). Separate trials, not a head-to-head; TRIUMPH-5 tests that directly.
On this page11 sections
| Item | Value | Source |
|---|---|---|
| Retatrutide receptor targets | GIP, GLP-1 and glucagon receptors (triple agonist) | Cell Metabolism, Aug 18, 2022 |
| Tirzepatide receptor targets | GIP and GLP-1 receptors (dual agonist) | Eli Lilly, May 13, 2022 |
| Retatrutide regulatory status | Investigational; not approved by any regulator; U.S. submission planned Q1 2027 | Eli Lilly, Sep 29, 2026 |
| Zepbound FDA approval (weight) | Nov 8, 2023 | FDA, Nov 8, 2023 |
| Retatrutide half-life | Approximately 6 days (Phase 1b, type 2 diabetes) | The Lancet, Oct 27, 2022 |
| Tirzepatide half-life | About 5 days (Zepbound label section 12.3: 5–6 days) | DailyMed, Aug 28, 2026 |
| Retatrutide Phase 3 ladder | 2 → 4 → 6 → 9 → 12 mg, one step every 4 weeks (trial protocol) | Eli Lilly, Dec 11, 2025 |
| Zepbound label ladder | 2.5 mg for 4 weeks, then 5 mg; +2.5 mg steps after ≥4 weeks; max 15 mg | DailyMed, Aug 28, 2026 |
| TRIUMPH-1, 12 mg, week 80 | −28.3% (efficacy estimand); −25.0% (treatment-regimen) vs −2.2% / −3.9% placebo | Eli Lilly, May 21, 2026 |
| SURMOUNT-1, 15 mg, week 72 | −20.9% vs −3.1% placebo (treatment-regimen estimand) | N Engl J Med, Jul 21, 2022 |
| Head-to-head trial | TRIUMPH-5 (NCT06662383): active, not recruiting; no results posted | ClinicalTrials.gov, Jul 20, 2026 |
Also useful: Retatrutide level plotter, Tirzepatide level plotter, GLP-1 level plotter (all compounds).
Retatrutide and tirzepatide are both once-weekly Eli Lilly peptides for obesity, and both act on the GIP and GLP-1 receptors. Retatrutide also activates the glucagon receptor. The bigger difference is status: tirzepatide is an approved medicine with an FDA label, while retatrutide is still a trial drug. The table below puts the published facts side by side. Retatrutide numbers come from Lilly releases and journal abstracts; tirzepatide numbers come from the FDA labels and the SURMOUNT-1 paper. For the full profiles, see the retatrutide hub and the tirzepatide hub.
Side-by-side comparison table
| Item | Retatrutide | Tirzepatide |
|---|---|---|
| Receptor targets | GIP, GLP-1, glucagon | GIP, GLP-1 |
| Status | Investigational; not approved anywhere | FDA approved (Mounjaro 2022, Zepbound 2023) |
| Brand names | None | Zepbound, Mounjaro |
| Half-life | Approximately 6 days | About 5 days (Zepbound label: 5–6 days) |
| Time to peak | About 1–3 days (single-dose study) | Median 24 hours, range 8–72 hours (Zepbound label) |
| Starting dose | 2 mg weekly (trial protocol) | 2.5 mg weekly for 4 weeks (label) |
| Step interval | Every 4 weeks (trial protocol) | At least 4 weeks per step (label) |
| Dose steps | 2, 4, 6, 9, 12 mg | 2.5, 5, 7.5, 10, 12.5, 15 mg |
| Pivotal obesity trial | TRIUMPH-1 (NCT05929066), 2,339 randomized | SURMOUNT-1, 2,539 participants |
| Primary timepoint | 80 weeks | 72 weeks |
| Top-dose weight change, treatment-regimen estimand | −25.0% (12 mg) vs −3.9% placebo | −20.9% (15 mg) vs −3.1% placebo |
| Top-dose weight change, efficacy estimand | −28.3% (12 mg) vs −2.2% placebo | Not verified in our sources |
| Nausea, top dose vs placebo | 42.4% vs 14.8% (80 weeks) | 28% vs 8% (label pooled table) |
| Discontinuation due to adverse events, top dose | 11.3% vs 4.9% placebo | 6.2% vs 2.6% placebo |
Sources: TRIUMPH-1 figures (Eli Lilly, May 21, 2026), half-life (The Lancet, Oct 27, 2022), retatrutide time to peak from Lilly’s Phase 2 protocol summary of the single-dose study (Eli Lilly, hosted on ClinicalTrials.gov, Aug 29, 2022), Zepbound label (DailyMed, Aug 28, 2026), SURMOUNT-1 (N Engl J Med, Jul 21, 2022).
An estimand is the exact question an analysis answers. The efficacy estimand asks what would have happened if everyone had stayed on the drug. The treatment-regimen estimand counts everyone who was randomized, whether or not they kept taking it, so its numbers are usually lower. Lilly press releases lead with the efficacy estimand; journals lead with the treatment-regimen estimand. The SURMOUNT-1 abstract reports the treatment-regimen estimand, so the fair like-for-like pair is −25.0% for retatrutide 12 mg and −20.9% for tirzepatide 15 mg (N Engl J Med, Sep 29, 2026).
Why this is not a head-to-head result
The two pivotal trials were run separately, years apart, with different people. Any comparison across them carries these caveats:
- Length. TRIUMPH-1 measured weight at 80 weeks; SURMOUNT-1 at 72 weeks. Eight more weeks of treatment can add weight loss on its own.
- Starting weight. TRIUMPH-1 participants averaged 112.7 kg with a BMI of 40.0 (Eli Lilly, May 21, 2026). SURMOUNT-1 participants averaged 104.8 kg (N Engl J Med, Jul 21, 2022).
- Enrollment criteria. TRIUMPH-1 enrolled adults with obesity or overweight plus at least one weight-related condition, without diabetes. SURMOUNT-1 enrolled adults with obesity or overweight without diabetes. The criteria are similar but not identical.
- Analysis. Even within one estimand, missing-data rules differ between trials. The Zepbound label notes that its Study 1 numbers use hybrid retrieved-dropout imputation.
- Side-effect tables. The TRIUMPH-1 rates are Lilly’s 80-week topline. The Zepbound label table pools SURMOUNT-1 and SURMOUNT-2, and SURMOUNT-2 enrolled people with type 2 diabetes.
The honest summary: retatrutide’s trial numbers are higher, but no one has yet shown how the two drugs compare in the same people.
TRIUMPH-5: the direct comparison
Lilly registered TRIUMPH-5 (NCT06662383) to compare retatrutide with tirzepatide in adults who have obesity (ClinicalTrials.gov, Jul 20, 2026). When we retrieved the record on Oct 19, 2026, ClinicalTrials.gov listed it as active, not recruiting, with primary completion estimated for November 2026. No results have been posted or announced. Until they are, any claim that one drug “beats” the other rests on cross-trial comparison.
Mechanism: two receptors vs three
GLP-1 and GIP are gut hormones released after meals. Both drugs mimic them at their receptors. Lilly’s 2022 approval release called tirzepatide the first GIP and GLP-1 receptor agonist (Eli Lilly, May 13, 2022).
Retatrutide adds the glucagon receptor. In laboratory testing, it showed balanced glucagon and GLP-1 receptor activity but more GIP receptor activity (Cell Metabolism, Aug 18, 2022). Glucagon receptor activity is the part that is new. It is one reason retatrutide is studied as a separate class of drug rather than a stronger tirzepatide. Online sellers sometimes call it “GLP-3”; that is a nickname, not a hormone. See GLP-3 vs GLP-1.
Dose ladders compared
Both drugs start low and climb in 4-week steps. For retatrutide this is how the trials were run; for tirzepatide it is the FDA label. Neither column is personal advice.
| Weeks | Retatrutide (TRIUMPH protocol) | Tirzepatide (Zepbound label) |
|---|---|---|
| 1–4 | 2 mg | 2.5 mg |
| 5–8 | 4 mg | 5 mg |
| 9–12 | 6 mg | 7.5 mg |
| 13–16 | 9 mg | 10 mg |
| 17–20 | 12 mg (top dose) | 12.5 mg |
| 21 onward | 12 mg | 15 mg (top dose) |
Sources: Lilly’s TRIUMPH-4 release describes the 2 mg start and 4-week steps used across the program (Eli Lilly, Dec 11, 2025); the Zepbound label sets the 2.5 mg start and 2.5 mg increments after at least 4 weeks (DailyMed, Aug 28, 2026).
Two differences stand out. Retatrutide’s trial arms ended at fixed targets of 4, 9 or 12 mg. Zepbound’s label names 5, 10 and 15 mg as maintenance doses, and the label lets a prescriber stay longer on any step. In Phase 2, retatrutide used a 2 → 4 → 8 → 12 mg ladder; Phase 3 replaced the 8 mg step with 6 and 9 mg.
- Weekly dose (published steps)
- Modeled amount (mg-eq)
- Stable window
- Weekly dose (published steps)
- Modeled amount (mg-eq)
- Stable window
To model either ladder with your own start date, use the retatrutide titration tool or the tirzepatide titration tool.
Half-life and modeled accumulation
A longer half-life means more of each weekly dose is still present when the next one arrives, so levels build higher before they level off. GLP Ladder’s model uses 6 days for retatrutide and 5 days for tirzepatide.
| Model value | Retatrutide | Tirzepatide |
|---|---|---|
| Half-life used | 6 days | 5 days |
| Time to peak used | 1 day | 1 day |
| Fraction of a dose left after 7 days | 0.4454 | 0.3789 |
| Weekly accumulation ratio | 1.8033 | 1.6101 |
| About 97% of steady state after 5 half-lives | About 30 days | About 25 days |
The Zepbound label states that steady state is reached after 4 weeks of once-weekly dosing (DailyMed, Aug 28, 2026), which matches the model. The model output is a relative amount in milligram-equivalents, not a blood concentration. See it plotted in the retatrutide plotter, the tirzepatide plotter, or both on one chart in the multi-compound plotter.
Side effects compared
| Adverse event | Retatrutide 12 mg (TRIUMPH-1, 80 wk) | Placebo | Tirzepatide 15 mg (Zepbound label pool) | Placebo |
|---|---|---|---|---|
| Nausea | 42.4% | 14.8% | 28% | 8% |
| Diarrhea | 32.0% | 13.5% | 23% | 8% |
| Constipation | 26.1% | 10.9% | 11% | 5% |
| Vomiting | 25.3% | 4.8% | 13% | 2% |
| Dysesthesia | 12.5% | 0.9% | Not in label table | — |
| Hair loss | Not reported in topline | — | 5% | 1% |
Sources: (Eli Lilly, May 21, 2026) (DailyMed, Aug 28, 2026)
Dysesthesia means abnormal skin sensations such as tingling or burning. It is a signal seen with retatrutide that is not typical of older GLP-1 drugs. In TRIUMPH-4, a 68-week knee osteoarthritis trial, it reached 20.9% on 12 mg vs 0.7% on placebo (Eli Lilly, Dec 11, 2025).
Discontinuation due to adverse events in TRIUMPH-1 rose with dose: 4.1% on 4 mg, 6.9% on 9 mg and 11.3% on 12 mg, vs 4.9% on placebo. In SURMOUNT-1 it was 4.3%, 7.1% and 6.2% on 5, 10 and 15 mg, vs 2.6% on placebo (N Engl J Med, Jul 21, 2022). More detail is in the retatrutide side effects guide and the tirzepatide side effects guide.
In type 2 diabetes
TRIUMPH-2 tested retatrutide in adults with type 2 diabetes plus obesity or overweight. At 80 weeks, 12 mg averaged −20.8% under the efficacy estimand (Eli Lilly, Sep 29, 2026) and −18.8% under the treatment-regimen estimand (The Lancet, Sep 29, 2026), vs −4.0% and −5.1% on placebo. That is smaller than the −28.3% the same dose reached in TRIUMPH-1, which enrolled people without diabetes, and it is another reason not to mix diabetes and non-diabetes results. Tirzepatide’s diabetes program (SURPASS) reported weight in kilograms against active comparators, so its numbers do not line up with TRIUMPH-2.
Status and legal availability
Tirzepatide is sold as Mounjaro, approved May 13, 2022 for type 2 diabetes (Eli Lilly, May 13, 2022), and Zepbound, approved Nov 8, 2023 for chronic weight management (FDA, Nov 8, 2023) and Dec 20, 2024 for obstructive sleep apnea in adults with obesity (FDA, Dec 20, 2024). Mounjaro is not indicated for weight loss. Compounded tirzepatide is not FDA approved, and FDA had received more than 730 adverse-event reports linked to it as of May 31, 2026 (FDA, Oct 1, 2026).
Retatrutide is not approved anywhere. Lilly said on Aug 12, 2026 that no retatrutide medicine has been approved by any regulator (Eli Lilly, Aug 12, 2026), and on Sep 29, 2026 that it plans a U.S. submission in the first quarter of 2027 (Eli Lilly, Sep 29, 2026). Products sold online as “research use only” retatrutide are not the trial drug, and FDA has said compounded retatrutide does not qualify for the compounding exemptions (FDA, Sep 9, 2025). For the full timeline, see is retatrutide FDA approved.
If you take tirzepatide, talk to your prescriber before changing anything based on trial comparisons.
Frequently asked questions
Retatrutide vs tirzepatide: which causes more weight loss?
- No head-to-head result exists yet. In separate placebo-controlled trials, retatrutide 12 mg averaged −25.0% at 80 weeks in TRIUMPH-1 and tirzepatide 15 mg averaged −20.9% at 72 weeks in SURMOUNT-1, both under the treatment-regimen estimand. The trials differ in population, length and baseline weight, so the difference is a cross-trial comparison. TRIUMPH-5 (NCT06662383) compares the two directly; it had not posted results as of Oct 19, 2026.
Is retatrutide FDA approved like tirzepatide?
- No. Tirzepatide is FDA approved as Mounjaro (type 2 diabetes, May 13, 2022) and Zepbound (chronic weight management, Nov 8, 2023; obstructive sleep apnea, Dec 20, 2024). Retatrutide is investigational. Lilly said on Aug 12, 2026 that no retatrutide medicine has been approved by any regulator, and on Sep 29, 2026 that it plans a U.S. submission in the first quarter of 2027.
Is there a head-to-head trial of retatrutide vs tirzepatide?
- Yes. TRIUMPH-5 (NCT06662383) is a Lilly study comparing retatrutide with tirzepatide in adults who have obesity. ClinicalTrials.gov listed it as active, not recruiting when retrieved on Oct 19, 2026, with primary completion estimated for November 2026. No results have been posted or announced.
How does the retatrutide dosing schedule compare with tirzepatide?
- In Phase 3 trials, retatrutide started at 2 mg once weekly and stepped up every 4 weeks through 4, 6 and 9 mg to 12 mg, per Lilly's releases. That is a trial protocol, not a recommendation. The Zepbound label starts at 2.5 mg weekly for 4 weeks, then 5 mg, with 2.5 mg increases after at least 4 weeks on the current dose, up to 15 mg. Talk to your prescriber about any tirzepatide dose.
Does retatrutide have more side effects than tirzepatide?
- Both mostly cause gastrointestinal effects. In TRIUMPH-1, nausea was 42.4% on 12 mg vs 14.8% on placebo over 80 weeks, and dysesthesia (abnormal skin sensation) was 12.5% vs 0.9%. The Zepbound label reports nausea of 28% on 15 mg vs 8% on placebo in a pooled table. The data sources, populations and durations differ, so these rates are not a direct comparison.
What is the half-life of retatrutide vs tirzepatide?
- Retatrutide's half-life is approximately 6 days, from a Phase 1b study published in The Lancet in 2022. Tirzepatide's is about 5 days: the Mounjaro label says approximately 5 days, and section 12.3 of the Zepbound label says 5 to 6 days. Both support once-weekly schedules.
Sources
- Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial. Eli Lilly and Company (via PR Newswire; also investor.lilly.com), May 21, 2026. Accessed Oct 19, 2026.
- Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. N Engl J Med (abstract via PubMed PMID 42814954; doi:10.1056/NEJMoa2604169), Sep 29, 2026. Accessed Oct 19, 2026.
- Lilly's triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful Phase 3 trial. Eli Lilly and Company (via PR Newswire), Dec 11, 2025. Accessed Oct 19, 2026.
- Lilly's triple agonist, retatrutide, delivered substantial weight loss and A1C reduction, underscoring its potential promise for people with obesity and type 2 diabetes. Eli Lilly and Company (via PR Newswire; also investor.lilly.com), Sep 29, 2026. Accessed Oct 19, 2026.
- Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial. The Lancet 2026;408(10563):1455-1472 (abstract via PubMed PMID 42810372; doi:10.1016/S0140-6736(26)01861-1), Sep 29, 2026. Accessed Oct 19, 2026.
- Lilly calls on online platforms, payment companies and regulators to shut down the illegal retatrutide black market. Eli Lilly and Company (via PR Newswire), Aug 12, 2026. Accessed Oct 19, 2026.
- LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. The Lancet 2022;400(10366):1869-1881 (abstract via PubMed PMID 36354040; doi:10.1016/S0140-6736(22)02033-5), Oct 27, 2022. Accessed Oct 19, 2026.
- LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Cell Metabolism 2022;34(9):1234-1247.e9 (abstract via PubMed PMID 35985340; doi:10.1016/j.cmet.2022.07.013), Aug 18, 2022. Accessed Oct 19, 2026.
- A Study of Retatrutide (LY3437943) Compared to Tirzepatide (LY3298176) in Adults Who Have Obesity (TRIUMPH-5). ClinicalTrials.gov (U.S. NLM), Jul 20, 2026. Accessed Oct 19, 2026.
- Study Protocol J1I-MC-GZBF(b) for NCT04881760 (Prot_000.pdf). Eli Lilly and Company, hosted on ClinicalTrials.gov, Aug 29, 2022. Accessed Oct 19, 2026.
- Warning Letter: ASN-LABS, MARCS-CMS 716459. U.S. Food and Drug Administration, Sep 9, 2025. Accessed Oct 19, 2026.
- ZEPBOUND (tirzepatide) injection, for subcutaneous use - Full Prescribing Information, Medication Guide and Instructions for Use (DailyMed SPL set ID 487cd7e7-434c-4925-99fa-aa80b1cc776b, version 40). U.S. National Library of Medicine (DailyMed) / Eli Lilly and Company, Aug 28, 2026. Accessed Oct 19, 2026.
- MOUNJARO (tirzepatide) injection, for subcutaneous use - Full Prescribing Information, Medication Guide and Instructions for Use (DailyMed SPL set ID d2d7da5d-ad07-4228-955f-cf7e355c8cc0, version 40). U.S. National Library of Medicine (DailyMed) / Eli Lilly and Company, Aug 27, 2026. Accessed Oct 19, 2026.
- Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med 2022;387(3):205-216 (Jastreboff AM et al.; PubMed PMID 35658024; doi:10.1056/NEJMoa2206038), Jul 21, 2022. Accessed Oct 19, 2026.
- FDA approves Lilly's Mounjaro™ (tirzepatide) injection, the first and only GIP and GLP-1 receptor agonist for the treatment of adults with type 2 diabetes. Eli Lilly and Company (investor.lilly.com), May 13, 2022. Accessed Oct 19, 2026.
- FDA Approves New Medication for Chronic Weight Management. U.S. Food and Drug Administration, Nov 8, 2023. Accessed Oct 19, 2026.
- FDA Approves First Medication for Obstructive Sleep Apnea. U.S. Food and Drug Administration, Dec 20, 2024. Accessed Oct 19, 2026.
- FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss. U.S. Food and Drug Administration, Oct 1, 2026. Accessed Oct 19, 2026.