Tirzepatide vs retatrutide: what the trials show
- By Reed Calder
- Last reviewed Oct 30, 2026
- 17 sources checked: trials, FDA records, trial registry
In short
Tirzepatide, sold as Mounjaro and Zepbound, acts on two gut-hormone receptors, GLP-1 and GIP, and is FDA-approved. Retatrutide adds a third, glucagon, and is still in trials. In separate trials of adults with obesity, the top dose of retatrutide averaged 25.0% weight loss over 80 weeks and tirzepatide 20.9% over 72 weeks. They haven’t been tested against each other yet: Lilly’s head-to-head trial is still running.
EvidenceCellAnimalHumanLarge randomized trials for both; no head-to-head result yet
Both drugs are made by Eli Lilly. Putting two trial results next to each other doesn’t tell you which drug works better. This page lines up what each was tested in, why those numbers can’t settle it, the side effects that do differ, the trial that will compare them directly, and what is known about switching from one to the other.
Tirzepatide and retatrutide side by side
| Tirzepatide | Retatrutide | |
|---|---|---|
| Brand names | Mounjaro (diabetes), Zepbound (weight, sleep apnea) | None; code name LY3437943, nicknamed “reta” |
| Receptors it acts on | GLP-1 and GIP (two) | GLP-1, GIP and glucagon (three) |
| FDA status | Approved: Mounjaro May 2022, Zepbound November 2023, sleep apnea December 2024 | Not approved; Lilly plans to apply in early 2027 |
| Largest weight trial, top dose | 20.9% at 15 mg, 72 weeks | 25.0% at 12 mg, 80 weeks |
| Given | Injection under the skin, once a week | Injection under the skin, once a week, in trials |
| Longest data | About 3 years (176 weeks) | About 80 weeks |
| Heart outcome trial | Done: matched an older drug with proven heart benefit | Still running |
| Legal ways to get it | Prescription | Clinical trials only |
Sources for each row are in the sections below and the source list.
Weight loss, trial by trial
The two biggest weight trials were run the same way: adults with obesity but without diabetes, a placebo group, a slow dose increase, and results counted for everyone assigned the drug, including people who stopped.
| Tirzepatide (SURMOUNT-1) | Retatrutide (TRIUMPH-1) | |
|---|---|---|
| People | 2,539 | 2,339 |
| Length | 72 weeks | 80 weeks |
| Low dose | 15.0% (5 mg) | 17.6% (4 mg) |
| Middle dose | 19.5% (10 mg) | 23.7% (9 mg) |
| Top dose | 20.9% (15 mg) | 25.0% (12 mg) |
| Placebo | 3.1% | 3.9% |
| Paper | Jastreboff et al., 2022 | Jastreboff et al., 2026 |
You’ll also see 28.3% for retatrutide. That figure counts only people who kept taking the drug as planned (HCPLive, May 2026), so it is higher. Setting it against tirzepatide’s 20.9%, which counts everyone, overstates the gap. Compare numbers counted the same way.
EvidenceCellAnimalHumanTwo separate randomized trials
Why the numbers can’t pick a winner
Retatrutide’s numbers are higher, and it may well turn out stronger. But two separate trials can’t prove it:
- Different lengths. TRIUMPH-1 ran 8 weeks longer. That’s small, but it’s one more way the numbers aren’t measured on the same scale.
- Different years and people. SURMOUNT-1 started in December 2019; TRIUMPH-1 started in July 2023, with different sites and volunteers.
- Different dose ladders. Neither trial tested the other drug’s doses, so “12 mg of one equals X mg of the other” charts online aren’t based on a study.
- Same sponsor. Lilly paid for both, which doesn’t make either wrong but means no independent trial exists for retatrutide yet.
A head-to-head trial, with people randomly given one drug or the other, is the only way to settle which works better.
The head-to-head trial: TRIUMPH-5
Lilly is already running that trial. TRIUMPH-5 randomly assigns about 800 adults with obesity to retatrutide or tirzepatide, with neither the participants nor the doctors knowing which, and measures weight change at 80 weeks. It started in November 2024, has finished enrolling, and its main results are expected around November 2026, by the trial’s own estimate. No results have been posted (ClinicalTrials.gov NCT06662383).
A second, much larger trial is testing both drugs, each against placebo, in about 4,500 people with fatty liver disease, looking at serious liver outcomes over roughly four years. It runs to 2030 or later.
EvidenceCellAnimalHumanRunning; no results yet
We’ll update this page when TRIUMPH-5 reports.
Side effects compared
- Both are mostly digestive. Nausea, diarrhea, vomiting and constipation were the most common on both, rose with the dose, and came mostly during the dose increases (Zepbound label; Bellido et al., 2026).
- Skin sensations are the clearest difference. Dysesthesia, tingling, burning or touch-sensitive skin, was rare on tirzepatide and affected up to about 1 in 8 people on the top dose of retatrutide; Lilly says most cases were mild (HCPLive, 2026).
- Heart rate. Tirzepatide raised resting heart rate by 1 to 3 beats a minute on average. Retatrutide’s rise was dose-related in its phase 2 trial, peaked around 24 weeks and then eased (Jastreboff et al., 2023).
- Thyroid warning. Tirzepatide’s label carries a boxed warning because it caused thyroid C-cell tumors in rats; whether it does in people is unknown. Retatrutide has no label yet.
These come from different trials, so small gaps in nausea or quitting rates may not be real differences. The skin sensation gap is large enough that it probably is.
Sleep apnea, diabetes and the heart
Sleep apnea
Tirzepatide cut breathing pauses by about 25 to 29 an hour over 52 weeks, against about 5 on placebo, in people with moderate to severe sleep apnea, and is approved for it (Malhotra et al., 2024). Retatrutide cut them by about 23 to 34 an hour, against about 10 on placebo, over 80 weeks (Grunstein et al., 2026).
Diabetes
Over three years, 1.3% of people with prediabetes on tirzepatide developed type 2 diabetes, against 13.3% on placebo (Jastreboff et al., 2025). Retatrutide’s diabetes trials lowered blood sugar and weight (Bellido et al., 2026), but nothing that long has been reported.
Against semaglutide (Wegovy, Ozempic)
Both have beaten semaglutide head to head. Tirzepatide: 20.2% against 13.7% in 751 adults with obesity, published (Aronne et al., 2025). Retatrutide: 19.5% to 20.9% against 9.4% in people with diabetes, counting only people who stayed on treatment, released by Lilly but not yet published (Drugs.com summary, Oct 2026).
The heart
In 13,165 people with diabetes and heart disease, tirzepatide was at least as good as dulaglutide, an older drug known to cut heart attacks and strokes: 12.2% against 13.1% had one, or died of heart causes (Nicholls et al., 2025). Retatrutide’s heart outcome trial is still running.
EvidenceCellAnimalHuman
Switching from tirzepatide to retatrutide
We found no published study of people switching from tirzepatide to retatrutide, and no official conversion chart. The washout periods and “equivalent dose” tables you’ll see online aren’t based on a study.
- What the trials did: every retatrutide trial started people at 2 mg and raised the dose every four weeks, because starting high caused more nausea (Jastreboff et al., 2023). That’s how the trials were run, not instructions for anyone.
- Taking both at once: Zepbound’s label says not to combine it with any other GLP-1 drug, and retatrutide acts on the same two receptors plus one (Zepbound label).
- The legal route: outside a trial, there is no legal way to switch to retatrutide yet. If you’re on tirzepatide and want to try it, ask your doctor about enrolling in a trial.
Legal status and online products
- Tirzepatide needs a prescription to be sold legally for use in people, as Mounjaro, Zepbound or a compounded version. Compounded copies were widely allowed during a shortage; the FDA declared the shortage over and gave compounders until March 19, 2025 at the latest to stop (FDA). It’s also sold online without a prescription, as “research use only” powder (see below).
- Retatrutide can’t be compounded at all under federal law, and the FDA has sent warning letters to telehealth firms and suppliers selling it (FDA, 2026).
- “Research use only” products. The FDA has warned companies selling tirzepatide and retatrutide labeled “for research purposes” to people with dosing instructions (FDA, 2026). No regulator checks those products, so quality depends on the seller. Our guide to what to look for explains the legal routes and how to check a lab report.
- People do take both outside trials and post about it, but those reports aren’t studies: there’s no comparison group, and doses and products vary (Sehgal et al., 2026).
What’s still unknown
- Which drug causes more weight loss when tested side by side (TRIUMPH-5 should answer this).
- Whether retatrutide protects the heart, as tirzepatide has been shown to match an older drug that does.
- Retatrutide’s effects beyond about two years.
- What happens when people switch from one to the other.
- Whether the extra skin and heart rate effects of retatrutide matter over the long term.
Retracted and flagged studies
We checked every study cited here against PubMed and the Retraction Watch database, and we recheck them every month. None has been retracted or flagged; the 2024 sleep apnea paper has a routine published correction. The retatrutide studies are checked on our retatrutide page.
Bring your questions to other researchers
Our forum opens once 100 researchers join the waitlist. Members post studies, ask what they actually found, and answer with sources.
Questions
Is retatrutide better than tirzepatide?
It caused more weight loss in its own trials, 25.0% against 20.9% at the top doses, but they were separate trials. The head-to-head trial, TRIUMPH-5, hasn’t reported yet. Tirzepatide is approved and has longer safety data.
What is the difference between tirzepatide and retatrutide?
Tirzepatide acts on two hormone receptors, GLP-1 and GIP. Retatrutide adds a third, glucagon, which is thought to raise the energy the body burns. Tirzepatide is FDA-approved; retatrutide is still in trials.
Is retatrutide a GLP-3?
There is no hormone called GLP-3. “GLP-3” is a nickname for retatrutide’s three targets: GLP-1, GIP and glucagon.
Is retatrutide the same as Zepbound or Mounjaro?
No. Zepbound and Mounjaro are brand names for tirzepatide. Retatrutide is a different molecule, also from Lilly, with no brand name yet.
Can you switch from tirzepatide to retatrutide?
No study has tested switching, and retatrutide is only legally available in clinical trials. Trials started everyone at 2 mg and raised the dose slowly.
Can you take tirzepatide and retatrutide together?
No study has tested it. Zepbound’s label says not to combine it with any other GLP-1 drug, and retatrutide acts on the same receptors.
When will retatrutide be approved?
Lilly plans to apply to the FDA in early 2027, and reviews usually take months after that (HCPLive, July 2026).
Sources
- Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-16. PubMed 35658024
- Jastreboff AM, et al. Tirzepatide for obesity treatment and diabetes prevention. N Engl J Med. 2025;392(10):958-71. PubMed 39536238
- Aronne LJ, et al. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med. 2025;393(1):26-36. PubMed 40353578
- Malhotra A, et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity. N Engl J Med. 2024;391(13):1193-205. PubMed 38912654
- Nicholls SJ, et al. Cardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes. N Engl J Med. 2025;393(24):2409-20. PubMed 41406444
- Jastreboff AM, et al. Retatrutide, a triple hormone receptor agonist, for treatment of obesity. N Engl J Med. 2026 (TRIUMPH-1). PubMed 42814954
- Bellido V, et al. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial. Lancet. 2026;408(10563):1455-72. PubMed 42810372
- Grunstein RR, et al. Retatrutide once weekly for treatment of obstructive sleep apnea. N Engl J Med. 2026. PubMed 42904878
- Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial. N Engl J Med. 2023;389(6):514-26. PubMed 37366315
- Sehgal NKR, et al. Self-reported adverse effects among social media users taking nonapproved retatrutide. JAMA Netw Open. 2026;9(10):e2638929. PubMed 42873503
- ClinicalTrials.gov. A study of retatrutide compared to tirzepatide in adults who have obesity (TRIUMPH-5), NCT06662383. Last updated July 20, 2026. Record
- Zepbound (tirzepatide) prescribing information, Eli Lilly, revised August 2026. DailyMed
- U.S. Food and Drug Administration. FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize. Content current as of April 1, 2026. FDA page
- U.S. Food and Drug Administration. FDA’s concerns with unapproved GLP-1 drugs used for weight loss. Content current as of October 1, 2026. FDA page
- HCPLive. Retatrutide meets weight loss endpoints in phase 3 obesity trial (TRIUMPH-1 topline). May 2026. Article
- HCPLive. Retatrutide meets phase 3 weight loss endpoints in 2 obesity trials. July 2026. Article
- Drugs.com. Retatrutide (summary of Lilly’s TRANSCEND-T2D-2 topline results). Updated October 30, 2026. Page
Last reviewed Oct 30, 2026. Approval and compounding status change often; we recheck this page when they do. Nothing here is medical advice; see our medical disclaimer. Found a mistake? Email editors@peptideresearchstudy.com.