Research material and lot documents.
Retatrutide vs tirzepatide comes down to receptors and evidence: retatrutide is an investigational agonist of three hormone receptors, and tirzepatide is an FDA-approved agonist of two, sold as Mounjaro and Zepbound.
Retatrutide, often shortened to reta, is described by Lilly as a single molecule that activates the GIP, GLP-1 and glucagon receptors. FDA's announcement of November 8, 2023 says that Zepbound activates the GLP-1 and GIP receptors. The 2022 paper on tirzepatide's phase 3 obesity trial calls it a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist. Both are once-weekly Lilly molecules in their trials. Sources: Lilly, What to know about retatrutide, FDA announcement, November 8, 2023 and PMID 35658024.
Tirzepatide is the active ingredient in both. FDA's announcement says tirzepatide is approved as Mounjaro for adults with type 2 diabetes, and FDA approved Zepbound on November 8, 2023 for chronic weight management in adults with obesity, or with overweight and at least one weight-related condition. Retatrutide has no FDA approval; the retatrutide FDA approval page quotes Lilly and FDA. Source: FDA announcement, November 8, 2023.
Each trial compared its own drug with placebo, and neither compared the two drugs. Their lengths and populations differ.
SURMOUNT-1 (tirzepatide): phase 3, 2539 adults with obesity or overweight and no diabetes, 72 weeks. Mean body-weight change at week 72 was -15.0% to -20.9% across the three tirzepatide groups, against -3.1% with placebo. Source: 2022 New England Journal of Medicine, PMID 35658024.
TRIUMPH-1 (retatrutide): phase 3, 2339 adults with obesity and no diabetes, 80 weeks. Mean body-weight change was -17.6% to -25.0% across the three retatrutide groups, against -3.9% with placebo. Source: 2026 New England Journal of Medicine, PMID 42814954.
Both papers report the treatment-regimen estimand in the intention-to-treat population. A 2026 systematic review in Annals of Internal Medicine covered randomized trials of at least 16 weeks in adults without diabetes. It reported placebo-subtracted weight loss of up to -19.0% for tirzepatide and -22.1% for retatrutide, and its authors wrote that heterogeneity precluded quantitative synthesis. Source: PMID 42673585.
TRIUMPH-5 is a phase 3, double-blind, randomized trial of retatrutide against tirzepatide in adults who have obesity. Its ClinicalTrials.gov record lists 800 planned participants, percent change in body weight at week 80 as the primary outcome, and an estimated primary completion date of November 2026. The record's last update was posted on July 20, 2026, and on October 15, 2026 it showed no posted results.
FDA approved Wegovy (semaglutide) for chronic weight management on June 4, 2021 (NDA 215256). Source: FDA approval package, NDA 215256. The retatrutide trial TRANSCEND-T2D-2 compares retatrutide with semaglutide in adults with type 2 diabetes. Its record lists 1,250 planned participants, an actual primary completion date of August 27, 2026 and no posted results.
The phase 2 type 2 diabetes trial included dulaglutide as an active comparator. The authors reported larger HbA1c reductions than with dulaglutide in two retatrutide groups, and larger weight decreases than with dulaglutide in every retatrutide group except the lowest. Source: 2023 Lancet, PMID 37385280.
The retatrutide trials page follows each published result, and the retatrutide side effects page lists the adverse events the authors reported.