Home / Comparisons / Tirzepatide vs Retatrutide: Approved vs Investigational
Tirzepatide vs Retatrutide: Approved vs Investigational
Tirzepatide is FDA-approved; retatrutide is still experimental. What trials show for each, why they can't be ranked yet, and their FDA status.
On this page
Side by side
| Question | Tirzepatide | Retatrutide |
|---|---|---|
| U.S. status | ||
| Strongest evidence | Human trials | Human trials |
| Status verified |
One of these drugs is on pharmacy shelves with a label. The other is still being tested, and some of its headline numbers come only from the company that makes it. Here is what can and can’t be said when you put them next to each other.
Key takeaways
- Tirzepatide is FDA-approved. Retatrutide is investigational and not FDA-approved for any use. Lilly, which makes both, says it plans to submit retatrutide to FDA in the first quarter of 2027. That is a company plan, not an approval timeline.
- We found no published head-to-head trial of the two. A trial of that kind is listed as still active, so any claim that one beats the other is not backed by a published comparison.
- Retatrutide’s published weight-loss averages are numerically larger, but they come from different trials with different designs. That is not a ranking.
- Tirzepatide has labeled uses beyond weight; retatrutide has none. Tirzepatide has trials in sleep apnea and heart events. Retatrutide has phase 3 results in type 2 diabetes and subgroup results in knee osteoarthritis and sleep apnea, and no published cardiovascular or kidney outcome results.
- Compounded tirzepatide is not FDA-approved. FDA says retatrutide cannot be used in compounding under federal law.
What is the difference between them?
| Tirzepatide | Retatrutide | |
|---|---|---|
| FDA status | Approved as Zepbound (weight, sleep apnea) and Mounjaro (type 2 diabetes) | Investigational; not approved for any use |
| What it acts on | Two hormone receptors (GIP and GLP-1) | Three hormone receptors (GIP, GLP-1 and glucagon) |
| Prescribing label with warnings | Yes. Boxed warning for thyroid C-cell tumors | None. Risks are known only from trials |
| Compounded versions | Not FDA-approved. Not on the shortage or 503B lists | FDA: cannot be used in compounding under federal law |
| Maker | Eli Lilly | Eli Lilly |
Sources: Zepbound label, Mounjaro label, FDA and a search of Drugs@FDA on Oct. 31, which found no product listed as retatrutide. That search cannot show whether an application is pending.
Can the weight-loss numbers be compared?
Only with care. Here is one published trial of each drug, in adults with obesity and no diabetes. This is not a head-to-head comparison, and the order of the columns isn’t a rank. The figures are each journal’s main analysis. Arms are shown as dose ranges; this guide does not give doses.
| Tirzepatide: SURMOUNT-1 | Retatrutide: TRIUMPH-1 | |
|---|---|---|
| People | 2,539 adults with obesity, or overweight plus a weight-related condition, no diabetes | 2,339 adults with obesity, no diabetes |
| Length | 72 weeks | 80 weeks |
| Average weight change, active arms | −15.0% to −20.9% depending on dose arm | −17.6% to −25.0% depending on dose arm |
| Placebo | −3.1% | −3.9% |
| Stopping because of side effects | 4.3% to 7.1% vs 2.6% | 4.1% to 11.3% vs 4.9% (company-reported) |
Why this is not a ranking:
- They are different trials. Different people, different lengths and different dose arms.
- Both figures use a treatment-regimen analysis, and that doesn’t make them comparable. The SURMOUNT-1 and TRIUMPH-1 abstracts both describe one. The trials still differ in people, length and dose arms.
- The side-effect rates come from different sources. The retatrutide stopping rates in TRIUMPH-1 are from Lilly’s release; the tirzepatide rates are from the journal.
- Lilly makes both drugs and paid for both trials. The retatrutide side-effect rates in TRIUMPH-1 come from the company.
Why do you see 28% for retatrutide?
Lilly’s May release gives 28.3% on the highest dose of TRIUMPH-1; the New England Journal of Medicine reports 25.0%. The company calls its higher figure the “efficacy estimand,” which it defines as the effect had all randomized participants remained on treatment. The journal figure uses the treatment-regimen estimand. Do not set the 28.3% beside the tirzepatide figures.
What about the retatrutide trial versus Ozempic?
On Oct. 28, 2026, Lilly reported topline results from an open-label trial of retatrutide against Ozempic in type 2 diabetes. It is a company result that has not been published in a journal, and it compares retatrutide with a different drug, not with tirzepatide.
What evidence goes beyond weight?
| Goal | Tirzepatide | Retatrutide |
|---|---|---|
| Sleep apnea with obesity | SURMOUNT-OSA: 469 adults, 52 weeks; apnea-hypopnea index fell 25.3 vs 5.3 events per hour without PAP therapy, and 29.3 vs 5.5 with it. FDA-approved use | In a TRIUMPH-1 subgroup of 243 people, the apnea-hypopnea index fell more than with placebo (differences of −24.7 and −22.5 events per hour in the intention-to-treat analysis for two dose arms). Not approved; not a dedicated trial |
| Knee osteoarthritis | We did not review this | In a TRIUMPH-1 subgroup of 574 people, pain improved more than with placebo. Not approved |
| Heart events | SURPASS-CVOT: non-inferior to dulaglutide, not superior | No results yet; a large outcomes trial is active |
| Type 2 diabetes | Approved as Mounjaro | Published phase 3 results; not approved |
| Lean mass | In a substudy of 160 people, about 25% of weight lost was lean mass | A phase 2 substudy in type 2 diabetes (funded by Lilly) says the share was similar to other obesity treatments; its abstract does not give the share |
Lean mass is not the same as muscle or strength, and neither set of analyses measured strength.
How do the risks compare?
We can’t compare them head to head, because retatrutide has no label and no long-term data.
- Tirzepatide: boxed warning for thyroid C-cell tumors, contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2, and warnings for severe gastrointestinal reactions, kidney injury from dehydration, gallbladder disease, pancreatitis and others (Zepbound label).
- Retatrutide, as seen in trials: dose-related nausea, abnormal skin sensations (dysesthesia), low blood pressure and a rise in heart rate. In TRIUMPH-2, six people on retatrutide and one on placebo died; investigators deemed the deaths unrelated to treatment (TRIUMPH-2). Long-term safety is unknown.
For each drug’s risks in more detail, see our guides to tirzepatide and retatrutide.
What about compounded versions?
- Tirzepatide: compounded versions are not FDA-approved, and FDA does not review compounded drugs for safety, effectiveness or quality before they are marketed. Tirzepatide is not on the FDA shortage list or the 503B list (FDA, April 1, 2026).
- Retatrutide: FDA says it “cannot be used in compounding under federal law” and has “not been found safe and effective for any condition” (FDA, Oct. 1, 2026). There is no FDA-approved retatrutide product to buy.
- HHS’s Oct. 30, 2026 interim compounding policy covers six other peptides and does not include either drug.
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Which claims are not supported?
- “Retatrutide beats tirzepatide.” No published comparison supports it, and the one trial that might is not finished.
- “Retatrutide is nearly approved.” Lilly says it plans to file in the first quarter of 2027.
- “You can get retatrutide from a compounding pharmacy.” FDA says no.
- “28% vs 21%.” That sets a company’s efficacy analysis beside a different trial’s figure.
- “Retatrutide is safer” or “tirzepatide is safer.” Retatrutide’s long-term safety is unknown, and no direct comparison exists.
What should you ask your doctor?
- Is an FDA-approved weight-management drug appropriate for me, and which uses are on its label?
- If I am interested in an experimental drug, is there a clinical trial for which I qualify, and what would taking part involve?
- If someone offers me retatrutide outside a trial, what is it, who made it, and how would anyone know what is in it?
Frequently asked questions
Is retatrutide stronger than tirzepatide?
Its published average weight loss is numerically larger, but the trials are different and no published head-to-head comparison exists.
Is retatrutide approved?
No. It is investigational.
Can you take retatrutide with tirzepatide?
We did not review combinations. The Zepbound label does not recommend combining tirzepatide with another GLP-1 product. Ask your prescriber about your own situation.
Is compounded tirzepatide the same as Zepbound?
No. Compounded drugs are not FDA-approved, which means FDA does not review them to evaluate their safety, effectiveness or quality before they reach patients.
Sources we checked
- Zepbound prescribing information (DailyMed, rev. 08/2026)FDA. Accessed .
- Mounjaro prescribing information (DailyMed)FDA. Accessed .
- SURMOUNT-1 trial (PubMed)PubMed. Accessed .
- SURMOUNT-OSA trial (PubMed)PubMed. Accessed .
- SURPASS-CVOT trial (PubMed)PubMed. Accessed .
- SURMOUNT-1 body composition substudy (PubMed)PubMed. Accessed .
- TRIUMPH-1 trial, retatrutide in obesity, NEJM (PubMed)PubMed. Accessed .
- TRIUMPH-2 trial, retatrutide in obesity and type 2 diabetes, Lancet (PubMed)PubMed. Accessed .
- Retatrutide body composition substudy, Lancet Diabetes Endocrinol 2025 (PubMed)PubMed. Accessed .
- Lilly press release on retatrutide TRIUMPH-1, May 21, 2026Press release. Accessed .
- Lilly press release on retatrutide TRIUMPH-2, Sept. 29, 2026Press release. Accessed .
- ClinicalTrials.gov NCT06662383 (retatrutide comparison trial, active)ClinicalTrials.gov. Accessed .
- ClinicalTrials.gov NCT06383390 (cardiovascular and renal outcomes trial, active)ClinicalTrials.gov. Accessed .
- Drugs@FDA (searched Oct. 31, 2026; no product listed as retatrutide)FDA. Accessed .
- FDA's concerns with unapproved GLP-1 drugs used for weight lossFDA. Accessed .
- FDA clarifies policies for compounders as national GLP-1 supply stabilizesFDA. Accessed .
- HHS: Enforcement Discretion Policy, with Appendices A and BOther. Accessed .
- TRANSCEND-T2D-1 trial, retatrutide in type 2 diabetes, Lancet (PubMed)PubMed. Accessed .
- Lilly press release on retatrutide TRANSCEND-T2D-2 vs Ozempic, Oct. 28, 2026Press release. Accessed .
- FDA: compounding laws and policiesFDA. Accessed .
Written and maintained by the Best Peptides For Editorial Team. How we rate evidence.