The Numbers From Each Trial Program

Semaglutide (STEP-1, Wilding et al., NEJM 2021): 2.4 mg weekly led to a mean weight reduction of 14.9% over 68 weeks.

Tirzepatide (SURMOUNT-1, Jastreboff et al., NEJM 2022): Over 72 weeks, dose-dependent reductions of 15% (5 mg), 19.5% (10 mg), and 22.5% (15 mg) were observed.

Retatrutide Phase 2 (Jastreboff et al., NEJM 2023): 22.8% (8 mg) and 24.2% (12 mg) over 48 weeks. The Phase 3 TRIUMPH-4 trial reported topline results in December 2025 of 26.4% (9 mg) and 28.7% (12 mg) over 68 weeks – these figures currently come from a press release; full peer-reviewed publication is still pending.

What a Direct Comparison Shows – and What It Doesn't

For tirzepatide vs. semaglutide, direct comparative trials now exist. A 2025 meta-analysis (Munawar et al., Cureus) with nearly 29,000 participants confirms a statistically significant advantage for tirzepatide over semaglutide.

For retatrutide, however, no study exists to date that tests it directly against semaglutide or tirzepatide. The percentages above come from separate trials with different populations, durations (48/68/72 weeks), and designs – ranking based on these numbers alone is not statistically sound.

Why More Receptors Tend to Show More Effect

Semaglutide activates only the GLP-1 receptor. Tirzepatide combines GLP-1 and GIP. Retatrutide adds a third pathway via the glucagon receptor, which studies associate with increased hepatic fat oxidation. Across the trial programs so far, this increasing receptor breadth tends to correlate with stronger weight reduction – while also changing the side-effect profile.

Different Approval Status

Semaglutid, Tirzepatid, Retatrutid." data-en="Semaglutide (Wegovy/Ozempic) and tirzepatide (Mounjaro/Zepbound) are FDA approved. Retatrutide is not – the Phase 3 TRIUMPH program is ongoing. Research product pages: Semaglutide, Tirzepatide, Retatrutide.">Semaglutid (Wegovy/Ozempic) und Tirzepatid (Mounjaro/Zepbound) sind FDA-zugelassen. Retatrutid ist es nicht – das Phase-3-Programm TRIUMPH läuft weiter. Produktseiten für die Forschung: Semaglutid, Tirzepatid, Retatrutid.

Sources

  • Wilding JPH, et al. NEJM. 2021;384(11):989–1002. PMID 33567185
  • Jastreboff AM, et al. NEJM. 2022;387(3):205–216. PMID 35658024
  • Jastreboff AM, et al. NEJM. 2023;389(6):514–526. PMID 37366315
  • Munawar N, et al. Cureus. 2025;17(6):e86080. PMID 40666599
  • Eli Lilly, TRIUMPH-4 Phase-3-Topline-Ergebnisse (Pressemitteilung, Dezember 2025) – Peer-Review-Publikation noch ausstehend.

References without a PMID can be located via the respective publisher.