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Retatrutide Beat Ozempic on A1C and Weight in First Head-to-Head Trial, Lilly Says

INDIANAPOLIS · Published November 2026 · 4 min read

  • Retatrutide
  • Ozempic
  • Semaglutide
  • Type 2 diabetes
  • Head-to-head
  • Phase 3
  • Eli Lilly
By Eli Marsden · Founding Editor
Editorially reviewed & fact-checked against primary sources · How we verify contentLast reviewed

Lilly said on October 28 that its investigational triple agonist retatrutide lowered blood sugar more than Ozempic and produced more than twice the weight loss in TRANSCEND-T2D-2, the first phase 3 trial to compare retatrutide directly with another incretin drug. These are company topline results that have not been peer-reviewed, and retatrutide is not FDA-approved.

Lilly announced positive topline results from TRANSCEND-T2D-2 on October 28, saying retatrutide met the primary and all key secondary endpoints against Ozempic 2 mg, the highest approved Ozempic dose for type 2 diabetes.[1] The figures below come from Lilly’s press release. Lilly says detailed results will be presented at a future medical meeting and published in a peer-reviewed journal; until then, no independent reviewer has checked them. Retatrutide is investigational and has not been approved by the FDA or any other regulator.[1]

The trial

  • Who: 1,298 adults with type 2 diabetes not controlled on metformin, with or without an SGLT2 inhibitor, and a starting A1C of 7.0% to 10.5%. Average baseline A1C was 8.3% and average weight 102.4 kg.[1]
  • Design: randomized 2:2:1 to weekly retatrutide 9 mg, retatrutide 12 mg or Ozempic 2 mg for 80 weeks. The trial was open-label, so participants and investigators knew which drug was given.[1]
  • Primary goal: showing that retatrutide 12 mg lowers A1C at least as well as Ozempic 2 mg (noninferiority).[1]

Results at 80 weeks

  • A1C: fell by an average of 2.2% on both retatrutide doses, against 1.8% on Ozempic.[1]
  • Weight: fell 19.5% on 9 mg and 20.9% on 12 mg, against 9.4% on Ozempic.[1]
  • Stopping because of side effects: 4.8% on 9 mg and 7.9% on 12 mg, against 2.7% on Ozempic.[1]
  • Common side effects: mostly gastrointestinal. Diarrhea affected 28.3% and 32.7% on retatrutide against 26.4% on Ozempic, and nausea 21.2% and 23.8% against 21.3%. Dysesthesia, an abnormal skin sensation, occurred in 4.8% and 6.5% against 2.7%.[1]

Lilly reports every number in the release under the efficacy estimand, which estimates what would have happened had everyone stayed on their assigned drug for the full 80 weeks. Figures that also count people who stopped treatment were not released.[1]

What it changes

Until now, every comparison of retatrutide with Ozempic in type 2 diabetes ran across separate trials with different comparators and durations, as our evidence review of retatrutide versus Ozempic explains; we have added the TRANSCEND-T2D-2 figures there. The earlier phase 2 diabetes trial, which used dulaglutide rather than semaglutide as its comparator, is covered in our review of retatrutide for type 2 diabetes. Lilly is also comparing retatrutide head-to-head with tirzepatide in TRIUMPH-5, which is still running.[1]

None of this makes retatrutide available. Lilly states that no one is legally allowed to sell it to patients.[1] The company plans to file with the FDA in early 2027, as our report on the retatrutide filing timeline sets out.

References

  1. 1.Eli Lilly and Company Lilly's retatrutide delivered greater A1C reduction and more than double the weight loss of Ozempic's highest approved dose in head-to-head trial PR Newswire. 2026. https://www.prnewswire.com/news-releases/lillys-retatrutide-delivered-greater-a1c-reduction-and-more-than-double-the-weight-loss-of-ozempics-highest-approved-dose-in-head-to-head-trial-302921328.html

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