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Retatrutide vs Tirzepatide — Trial Data

Retatrutide is a GIP/GLP-1/glucagon triple receptor agonist; tirzepatide is a GIP/GLP-1 dual receptor agonist. This page reports each compound's pivotal trial, retatrutide's topline Phase 3 data labelled as such, and adverse-event data from the same sources.

RetatrutideTirzepatide
MechanismGIP + GLP-1 + glucagon receptor agonistGIP + GLP-1 receptor agonist
Brand namesNone — investigationalMounjaro (type 2 diabetes), Zepbound (chronic weight management)
FDA statusNot approvedApproved (Mounjaro 2022, Zepbound 2023)
Pivotal trial result−24.2% at 12mg/48wk vs −2.1% placebo (Phase 2, Jastreboff et al. 2023, PMID 37366315)−20.9% at 15mg/72wk vs −3.1% placebo (SURMOUNT-1, Jastreboff et al. 2022, PMID 35658024)
Phase 3 statusTRIUMPH-4 topline: 28.7% at 12mg/68wk (Lilly release, Dec 11, 2025 — not yet peer-reviewed)Approved; SURPASS-CVOT (vs dulaglutide, active comparator) reported noninferior, PMID 41406444
Trial dosing1, 4, 8, or 12 mg subcutaneous once weekly (Phase 2)5, 10, or 15 mg subcutaneous once weekly (SURMOUNT-1)
On this page
  1. 1.Mechanism
  2. 2.Pivotal Trials
  3. 3.Retatrutide Phase 3 (Topline, Not Yet Peer-Reviewed)
  4. 4.Adverse Events
  5. 5.Approval Status
  6. 6.Dosing
  7. 7.Evidence Level
  8. 8.Reading These Figures
  9. 9.FAQ
  10. 10.References
  11. 11.Related comparisons

Mechanism

Tirzepatide activates the GIP and GLP-1 receptors. Retatrutide adds a third target, the glucagon receptor, reported to increase energy expenditure through a mechanism distinct from GLP-1-driven appetite suppression (Jastreboff et al. 2023, PMID 37366315).

Pivotal Trials

Retatrutide Phase 2 (Jastreboff et al. 2023, NEJM, PMID 37366315, NCT04881760): a double-blind, randomized, placebo-controlled trial of 338 adults with obesity, randomized to subcutaneous retatrutide (1, 4, 8, or 12 mg) or placebo once weekly for 48 weeks. At 48 weeks, mean weight change was −8.7% (1mg), −17.1% (4mg), −22.8% (8mg), and −24.2% (12mg), versus −2.1% with placebo.

SURMOUNT-1 (Jastreboff et al. 2022, NEJM, PMID 35658024, NCT04184622): a Phase 3, double-blind, randomized, placebo-controlled trial of 2,539 adults with obesity, randomized to subcutaneous tirzepatide (5, 10, or 15 mg) or placebo once weekly for 72 weeks, including a 20-week dose-escalation period. At week 72, mean weight change was −15.0% (5mg), −19.5% (10mg), and −20.9% (15mg), versus −3.1% with placebo.

Retatrutide Phase 3 (Topline, Not Yet Peer-Reviewed)

TRIUMPH-4 (Eli Lilly investor press release, December 11, 2025 — not yet peer-reviewed): 28.7% average weight loss reported at the 12 mg dose over 68 weeks in adults with obesity and knee osteoarthritis. No dated primary source for a specific TRIUMPH-4 dysesthesia percentage, liver-fat-reduction figure, or heart-rate change was located; those figures are not reproduced here.

Adverse Events

  • Retatrutide Phase 2: gastrointestinal events were dose-related, mostly mild to moderate, partially mitigated with a lower starting dose. Dose-dependent heart-rate increases peaked at 24 weeks and declined thereafter (PMID 37366315).
  • SURMOUNT-1 (tirzepatide): most common adverse events were gastrointestinal, occurring primarily during dose escalation. Discontinuation due to adverse events occurred in 4.3% (5mg), 7.1% (10mg), and 6.2% (15mg) of participants, versus 2.6% with placebo (PMID 35658024).

Approval Status

Retatrutide is investigational, with no FDA approval and no approved brand name. Tirzepatide is FDA-approved as Mounjaro (type 2 diabetes, 2022) and Zepbound (chronic weight management, 2023).

Dosing

In the trials above, retatrutide was dosed at 1, 4, 8, or 12 mg subcutaneously once weekly over 48 weeks; tirzepatide was dosed at 5, 10, or 15 mg subcutaneously once weekly over 72 weeks including a 20-week dose-escalation period. Dosing guides for each compound: retatrutide, tirzepatide.

Evidence Level

Both compounds: Human RCT. Retatrutide's Phase 2 trial and three Phase 3 trials (TRIUMPH-1, TRIUMPH-2, TRANSCEND-T2D-1) are published; TRIUMPH-4 is so far a topline company release. Tirzepatide's evidence includes both its pivotal Phase 3 obesity trial and post-approval cardiovascular-outcomes data (SURPASS-CVOT, PMID 41406444).

The retatrutide Phase 2 trial and SURMOUNT-1 enrolled different populations, at different doses, over different durations (48 weeks versus 72 weeks). Their reported figures are cross-trial comparisons, not a head-to-head result. No trial randomizing participants to retatrutide versus tirzepatide directly has been identified.

FAQ

What did the retatrutide Phase 2 trial report?

Jastreboff et al. 2023 (NEJM, PMID 37366315, NCT04881760) randomized 338 adults with obesity to subcutaneous retatrutide (1, 4, 8, or 12 mg) or placebo once weekly for 48 weeks. At 48 weeks, mean weight change was −24.2% with the 12 mg dose versus −2.1% with placebo. Gastrointestinal adverse events were dose-related and mostly mild to moderate; dose-dependent heart-rate increases peaked at 24 weeks and declined thereafter. No specific heart-rate figure in beats per minute was reported in the trial's abstract.

What did SURMOUNT-1 report for tirzepatide?

Jastreboff et al. 2022 (NEJM, PMID 35658024, NCT04184622) randomized 2,539 adults with obesity to subcutaneous tirzepatide (5, 10, or 15 mg) or placebo once weekly for 72 weeks. At week 72, mean weight change was −20.9% with the 15 mg dose versus −3.1% with placebo. The most common adverse events were gastrointestinal, occurring primarily during dose escalation; discontinuation due to adverse events occurred in 4.3–7.1% of tirzepatide groups versus 2.6% with placebo.

Is the retatrutide Phase 3 TRIUMPH-4 data published?

No. TRIUMPH-4's 28.7% weight-loss figure comes from an Eli Lilly investor press release dated December 11, 2025, not a peer-reviewed publication. It is reported here as a topline company release. No dated primary source for a specific TRIUMPH-4 dysesthesia percentage or heart-rate figure was located; those specific numbers are not reproduced on this page.

Can the Phase 2 retatrutide result and SURMOUNT-1 be compared directly?

Not as a head-to-head result. The retatrutide Phase 2 trial and SURMOUNT-1 enrolled different populations at different doses over different durations (48 weeks versus 72 weeks), so their reported percentages are cross-trial comparisons, not results from a shared trial. No trial randomizing participants to retatrutide versus tirzepatide directly has been identified.

References

  1. Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med. 2023;389(6):514-526. https://pubmed.ncbi.nlm.nih.gov/37366315/
  2. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-216. https://pubmed.ncbi.nlm.nih.gov/35658024/
  3. Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes (SURPASS-CVOT). N Engl J Med. 2025. PMID 41406444. DOI 10.1056/NEJMoa2505928. https://pubmed.ncbi.nlm.nih.gov/41406444/
  4. Eli Lilly. 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 (TRIUMPH-4). December 11, 2025. Topline results, not yet peer-reviewed. https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-weight-loss-average
Retatrutide ProfileTirzepatide Profile

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