Retatrutide vs tirzepatide vs semaglutide

Retatrutide, tirzepatide and semaglutide act on three, two and one hormone receptors. Tirzepatide and semaglutide are FDA-approved; retatrutide is investigational, not approved for any use, and no trial comparing it directly with either one has published its findings yet. Its phase 3 trials compared it with placebo, so its weight-loss numbers can’t be set fairly against the other two medicines’ trials.

If your prescriber has you on tirzepatide or semaglutide from a vial, the tirzepatide units calculator and the semaglutide units calculator turn the dose they gave you into syringe units. For the approved pair compared with each other, see semaglutide vs tirzepatide.

One, two or three receptors

Each is given as a once-weekly injection under the skin (semaglutide also comes as tablets). What sets them apart is how many hormone receptors each one switches on.

• Semaglutide acts on one: the GLP-1 receptor. It’s the active ingredient in Ozempic, Wegovy and Rybelsus (Wegovy label, Ozempic label).
• Tirzepatide acts on two: the GIP and GLP-1 receptors. It’s the active ingredient in Mounjaro and Zepbound (Zepbound label, Mounjaro label).
• Retatrutide acts on three. The TRIUMPH-1 authors describe it as “a triple-receptor agonist of glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, and glucagon receptors” (TRIUMPH-1). Its code name in early trials was LY3437943, and its half-life was “approximately 6 days,” which suits once-weekly dosing (phase 1b trial).

The third receptor, glucagon, is the one retatrutide adds over tirzepatide. More receptors doesn’t by itself mean more effect or fewer side effects; only trials can show that, and the direct comparisons haven’t reported yet.

Side by side

Sources: the Ozempic, Wegovy, Mounjaro and Zepbound labels; STEP 1, SURMOUNT-1, SURMOUNT-5 and the TRIUMPH-1 and TRIUMPH-2 papers; the FDA 2026 novel approvals list. Checked October 16, 2026.

“Retatrutide vs Ozempic” is the same question as retatrutide vs semaglutide: Ozempic is a semaglutide brand.

Where retatrutide stands with the FDA

As of October 16, 2026, retatrutide is not on the FDA’s list of 2026 novel drug approvals (current as of October 9, 2026), has no brand name, and has no FDA label (FDA). The FDA’s own wording:

“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.” (FDA)

So there’s no legal US prescription product to compare with Zepbound or Wegovy. The FDA has warned telehealth companies for marketing unapproved drugs such as retatrutide, and companies selling it “falsely labeled ‘for research purposes’ or ‘not for human consumption’”; it says those products “are of unknown quality and may be harmful” (FDA). It sent warning letters over “research use only” retatrutide in March and August 2026 (March 2026 letter, August 2026 letter). Whatever such a vial holds, none of the trial findings below describe it.

What each program’s trials found

Each medicine was tested against placebo in its own large trials. These are the averages each paper reports, with every trial’s own placebo group alongside:

Sources: STEP 1 (funded by Novo Nordisk); SURMOUNT-1; TRIUMPH-1; TRIUMPH-2; TRANSCEND-T2D-1. The tirzepatide and retatrutide trials were funded by Eli Lilly.

In TRANSCEND-T2D-1, HbA1c fell by 1.69 to 1.94 percentage points across the doses, compared with 0.81 on placebo, and “no severe hypoglycaemia was reported” (TRANSCEND-T2D-1). The earlier phase 2 trial (338 adults, 48 weeks) reported up to −24.2% at the highest dose tested vs −2.1% on placebo (phase 2 trial).

Beyond weight

TRIUMPH-1 also measured two conditions in the people who had them (TRIUMPH-1):

• Sleep apnea (243 people): breathing events per hour changed by −22.8 to −34.3 across the doses, vs −9.6 on placebo. Among the three medicines, only tirzepatide is FDA-approved for sleep apnea, as Zepbound (Zepbound label).
• Knee osteoarthritis (574 people): the WOMAC pain score changed by −3.2 to −3.6, vs −1.9 on placebo.

These are subgroups of one trial, not approvals. A dedicated knee osteoarthritis trial, TRIUMPH-4, finished in November 2025 but has no findings posted yet (ClinicalTrials.gov).

Why the numbers can’t be lined up

Putting −25.0% next to −20.9% and −14.9% is the comparison you’ll often see online. The table shows why it doesn’t hold:

• Different lengths. 68, 72 and 80 weeks. A longer trial has more time to show weight change.
• Different placebo groups. Placebo lost 2.4%, 3.1% and 3.9% in STEP 1, SURMOUNT-1 and TRIUMPH-1. The gap over placebo, not the raw figure, is what each trial measures.
• Different people. The same drug looks different in a different population: retatrutide’s top figure was −25.0% in people without diabetes (TRIUMPH-1) and −18.8% in people with type 2 diabetes (TRIUMPH-2).
• The same drug, a different trial. Tirzepatide averaged up to −20.9% in SURMOUNT-1 and −20.2% in SURMOUNT-5; semaglutide −14.9% in STEP 1 and −13.7% in SURMOUNT-5 (SURMOUNT-1, SURMOUNT-5, STEP 1).
• Different ways of counting. Trials can report a “treatment-regimen” figure, which keeps people in the count even if they stopped the drug, and an “efficacy” figure, which estimates the effect while people stay on it. In REDEFINE 4, a 2026 trial of CagriSema vs tirzepatide, the same tirzepatide group lost 23.6% on average one way and 25.5% the other, according to a company announcement from Novo Nordisk, which ran it (Novo Nordisk, REDEFINE 4). This page uses the treatment-regimen figures the papers report.

Only a trial that gives the drugs to similar people, for the same time, under the same rules can say which one did more. Among these three medicines, the only such trial with published findings is SURMOUNT-5: tirzepatide −20.2% vs semaglutide −13.7% over 72 weeks, open-label and funded by Eli Lilly (SURMOUNT-5). The details are in semaglutide vs tirzepatide.

The head-to-head trials still running

Sources: TRIUMPH-5 and TRANSCEND-T2D-2 on ClinicalTrials.gov.

TRIUMPH-5 is the trial that can answer “retatrutide vs tirzepatide” for weight. Until its findings are published, any claim that one beats the other comes from lining up separate trials.

Side effects: what’s known and what isn’t

Tirzepatide and semaglutide have FDA labels listing their warnings, including a boxed warning: both caused thyroid C-cell tumors in rodents, and it’s unknown whether they do in people (Zepbound label, Wegovy label). Retatrutide has no label, so no official warning list exists for it. What’s known comes from the trials.

In TRIUMPH-2, these were more common on retatrutide than on placebo (TRIUMPH-2):

• Diarrhea: 27% to 34% across the doses, vs 13%.
• Nausea: 14% to 28%, vs 8%.
• Unusual skin sensations (dysesthesia): 4% to 7%, vs 1%.
• Low blood pressure (hypotension): 1% to 6%, vs under 1%.
• Stopping for side effects or death: 4% to 12% across the doses (highest at the middle dose), vs 5% on placebo.
• Deaths: 6 on retatrutide and 1 on placebo; the investigators judged all of them unrelated to the study drug.

The phase 2 trial found that heart rate rose with dose, peaked at 24 weeks and declined after that; its digestive side effects were “dose-related” and mostly mild to moderate (phase 2 trial). The rates for tirzepatide and semaglutide in their own trials are in semaglutide vs tirzepatide. Long-term safety of retatrutide is still being studied.

Questions people ask