On October 28, 2026, the developer of retatrutide reported topline results from TRANSCEND-T2D-2. It is the first Phase 3 trial to compare retatrutide directly against semaglutide. The setting was type 2 diabetes, not obesity alone.
This is a summary of what the press release reported. It is not guidance of any kind.
Why a head-to-head trial matters
Most earlier retatrutide data compared the compound with placebo. A placebo comparison shows whether something moves a marker at all. An active comparator shows how it performs against an established reference compound. Semaglutide acts on one receptor (GLP-1). Retatrutide acts on three: GLP-1, GIP and glucagon. For background on those receptors, see GLP-1, GIP and glucagon: understanding receptor names.
Trial design
- Identifier: NCT06260722.
- Design: randomized, open-label, 80 weeks.
- Participants: 1,298 adults with type 2 diabetes not adequately controlled on metformin, with or without an SGLT2 inhibitor.
- Baseline A1C: eligibility ranged from 7.0% to 10.5%, with an average of 8.3%.
- Baseline weight: an average of 102.4 kg, with a BMI of 36.8.
- Study arms: two retatrutide arms (a lower and a higher target level) and one semaglutide comparator arm, randomized 2:2:1.
- Primary objective: show that the higher retatrutide arm was not inferior to the semaglutide arm on A1C reduction at 80 weeks.
Reported A1C results
- Both retatrutide arms lowered A1C by an average of 2.2 percentage points.
- The semaglutide arm lowered A1C by 1.8 points.
- The higher retatrutide arm met the primary objective, with a reported p-value below 0.001.
- The lower arm also showed greater reduction than semaglutide, described as nominally significant.
Reported weight results
- The lower retatrutide arm averaged a 19.5% reduction in body weight (20.1 kg).
- The higher retatrutide arm averaged 20.9% (21.5 kg).
- The semaglutide arm averaged 9.4% (9.5 kg).
- The release also reported greater improvement in non-HDL cholesterol, triglycerides and systolic blood pressure in the retatrutide arms.
All of these figures use the efficacy estimand. That approach estimates the effect in participants who stayed on their assigned treatment. The release did not report treatment-regimen estimand results, which count everyone randomized. Treatment-regimen figures are usually somewhat smaller.
What was reported on tolerability
Gastrointestinal events were the most common in every arm. Rates were broadly similar between retatrutide and semaglutide:
- Diarrhea: 28.3% and 32.7% in the retatrutide arms, 26.4% with semaglutide.
- Nausea: 21.2% and 23.8%, versus 21.3%.
- Vomiting: 10.2% and 15.0%, versus 13.2%.
- Constipation: 14.2% and 13.1%, versus 19.8%.
Dysesthesia, an altered skin sensation, appeared in 4.8% and 6.5% of the retatrutide arms, versus 2.7% with semaglutide. The same signal was noted in the earlier TRIUMPH trials.
Discontinuation because of adverse events was higher with retatrutide:
- 4.8% in the lower arm.
- 7.9% in the higher arm.
- 2.7% in the semaglutide arm.
Limits of this data
- Open-label design. Participants and investigators knew which compound was assigned.
- Topline only. Full results have not yet been presented at a meeting or published in a peer-reviewed journal.
- One estimand. Without the treatment-regimen figures, the picture is incomplete.
- Company source. These numbers come from the developer's press release and have not been independently reviewed.
How this fits with earlier results
TRANSCEND-T2D-2 is described as the sixth Phase 3 trial in which retatrutide met its goals. The three TRIUMPH obesity trials are summarized in Retatrutide in Phase 3. What the TRIUMPH trials reported. The earlier Phase 2 work is covered in our retatrutide research guide. For the comparator, see Semaglutide: mechanism from the label, outcomes from the trial.
A second head-to-head trial, TRIUMPH-5, is comparing retatrutide with tirzepatide. No results have been reported yet. Retatrutide is not approved by any regulator.
Why this matters for researchers
Head-to-head data gives laboratory work a sharper reference point than placebo data alone. It suggests how much a third receptor target may add over a single-receptor comparator on the same markers. Detailed tables in the eventual journal publication will be more useful than any topline summary.
Sources
- Eli Lilly press release, October 28, 2026
- AJMC, October 28, 2026
- Trial registry entry NCT06260722, ClinicalTrials.gov
- Life Science Daily, trial results roundup, October 30, 2026
For laboratory research use only. Not for human or veterinary use.
