Retatrutide's first phase 3 paper, published in September 2026, reported an average weight loss of 25.0% at the top dose [2]. That's a bigger number than any approved weight drug has posted in its own trials. So it's natural to ask whether it beats tirzepatide. The honest answer is that nobody knows yet, and right now only one of the two is a prescription you can fill.
No trial has put the two drugs side by side
Every number on this page comes from a trial that tested one drug against placebo. The trials enrolled different people, ran for different lengths of time and were measured at different points. Retatrutide's obesity trial lasted 80 weeks; tirzepatide's lasted 72.
That matters because the placebo groups differ too. In the retatrutide trial, people on placebo lost 3.9%; in the tirzepatide trial, 3.1% [2] [6]. A gap between two separate trials can come from the people enrolled as much as from the drug. Only a head-to-head trial settles it, and none has been published.
Weight loss in each drug's own trials
| Retatrutide (investigational) | Tirzepatide (approved) | |
|---|---|---|
| Receptors | GIP, GLP-1 and glucagon | GIP and GLP-1 |
| Obesity, no diabetes | TRIUMPH-1, 2,339 adults, 80 weeks: −17.6% (4 mg), −23.7% (9 mg), −25.0% (12 mg) vs −3.9% placebo [2] | SURMOUNT-1, 2,539 adults, 72 weeks: −15.0% (5 mg), −19.5% (10 mg), −20.9% (15 mg) vs −3.1% placebo [6] |
| Obesity with type 2 diabetes | TRIUMPH-2, 1,152 adults, 80 weeks: −11.9% to −18.8% vs −5.1% placebo [3] | SURMOUNT-2, 938 adults, 72 weeks: −12.8% (10 mg), −14.7% (15 mg) vs −3.2% placebo [7] |
| Blood sugar in type 2 diabetes | TRANSCEND-T2D-1, 537 adults, 40 weeks: A1C −1.69 to −1.94 points vs −0.81 on placebo [4] | SURPASS-2, 1,879 adults, 40 weeks: A1C −2.01 to −2.30 points vs −1.86 on semaglutide 1 mg [8] |
| Sleep apnea | Subgroup of 243 in TRIUMPH-1: −22.8 to −34.3 events an hour vs −9.6 on placebo [2] | SURMOUNT-OSA, 52 weeks: −25.3 events an hour vs −5.3 on placebo (people not using CPAP) [9] |
| FDA label | None | Mounjaro (May 2022), Zepbound (November 2023) |
| Compounding | Cannot be used in compounding under federal law (FDA) | Not on FDA's 503B bulks list; pharmacies may compound it only within narrow patient-specific limits |
| Developer | Eli Lilly | Eli Lilly |
Results come from separate trials and can't be ranked against each other. SURPASS-2 compared tirzepatide with semaglutide, not placebo, so its A1C figures aren't on the same footing as TRANSCEND-T2D-1's. All trials listed were funded by Eli Lilly.
The pattern holds across trials: retatrutide's averages run higher. In people with type 2 diabetes, who usually lose less weight on any of these drugs, the top retatrutide dose reached 18.8% at 80 weeks [3]. Tirzepatide's top dose reached 14.7% at 72 weeks in a similar group [7]. Lilly's own news release gave a higher TRIUMPH-2 figure using a different statistical method; the published paper's number is the one used here.
Three receptors vs two
Tirzepatide's label describes it as a GIP and GLP-1 receptor agonist: it mimics two gut hormones that raise insulin after meals and curb appetite [12]. Retatrutide adds a third target, the glucagon receptor [2]. Glucagon is the hormone that tells the liver to release stored energy, which is why researchers are studying whether the third receptor adds weight loss through energy use.
That's a research question, not an established benefit. The trial papers describe what the drug binds to; they don't show that the glucagon arm is what produced the extra weight loss. For the basics of the newer drug, see the retatrutide guide.
What is known about safety
Retatrutide's side effects in trials looked like the rest of the class. The most common were nausea, diarrhea and other stomach effects, mostly mild to moderate and tied to the dose [5]. In the 40-week diabetes trial, 2% to 5% of people on retatrutide stopped because of side effects, against none on placebo [4].
One signal stands out. Pulse went up in step with the dose during the phase 2 study, reaching its high point around week 24 before easing [5]. Trials of this size can't show what that means over years. There's no FDA label, so there's no approved list of warnings, no approved population and no postmarketing record yet.
Tirzepatide has all three. Its labels carry a boxed warning about thyroid C-cell tumors seen in rodents and warnings that include pancreatitis, gallbladder disease, kidney injury from dehydration and severe stomach reactions [12]. People have taken it under a prescription since 2022. More on that in tirzepatide side effects.
Where each drug stands with FDA
| Retatrutide | Tirzepatide | |
|---|---|---|
| FDA approval | Not approved for any use; not on FDA's 2026 novel approvals list (current as of October 9, 2026) [14] | Approved: Mounjaro for type 2 diabetes, Zepbound for weight and sleep apnea |
| Compounding | FDA: "cannot be used in compounding under federal law" | Shortage declared over on December 19, 2024; not on the 503B bulks list |
| Next step | Lilly says it plans to file for US approval in early 2027 (company statement) | Label updates continue; a heart-risk indication was added to Mounjaro in August 2026 |
Retatrutide and cagrilintide cannot be used in compounding under federal law. Additionally, these are not components of FDA-approved drugs and have not been found safe and effective for any condition.[13]
FDA also warns that illegally marketed GLP-1 drugs sold online may be counterfeit or contain the wrong ingredients [13]. Retatrutide sold as a "research" chemical is not the drug used in Lilly's trials, and its contents are unverified. The full legal picture is in retatrutide's legal status in the US.
On timing, Lilly has said publicly that it plans to submit retatrutide for US approval in the first quarter of 2027 [16]. FDA review usually takes many months after a filing, and a filing isn't an approval.
Retatrutide vs semaglutide: the same caveats apply
People ask the same question about semaglutide, the molecule in Wegovy. In its main obesity trial, STEP 1, semaglutide 2.4 mg produced 14.9% average weight loss at 68 weeks, against 2.4% on placebo [11]. Retatrutide's 25.0% at 80 weeks is larger, but again it comes from a separate trial.
Semaglutide and tirzepatide have been tested head to head: in SURMOUNT-5, tirzepatide produced 20.2% average weight loss against 13.7% for semaglutide at 72 weeks [10]. That comparison is in semaglutide vs tirzepatide. Retatrutide hasn't faced either drug in a published trial.
Switching from Zepbound or Mounjaro to retatrutide
Switching isn't an option for most people. Retatrutide isn't approved and a pharmacy can't compound it, so the routes are a clinical trial or Lilly's single-patient expanded access program, which a treating physician has to request [1]. If you're doing well on Zepbound or Mounjaro, that's an approved treatment with a known safety record.
The legitimate route to an investigational drug is a clinical trial. Trials are listed on ClinicalTrials.gov, the federal government's public trial listing, where each study shows who can join and where it runs [15]. A trial team decides eligibility, and stopping a current drug to join one is a conversation to have with your prescriber first.