Retatrutide Against Semaglutide in Type 2 Diabetes: What TRANSCEND-T2D-2 Shows
Published: November 3, 2026 · 3 min read · By Grey Peptides News Desk · ✓ Sourced
Eli Lilly reports that in TRANSCEND-T2D-2, the first phase 3 head-to-head for retatrutide, its weekly triple agonist lowered HbA1c more than semaglutide 2 mg, the highest Ozempic dose, and produced roughly twice the weight loss over 80 weeks: 19.5% on 9 mg and 20.9% on 12 mg against 9.4%. More people stopped retatrutide 12 mg for side effects. The figures are the company's own and have not been peer reviewed.
The trial
TRANSCEND-T2D-2 is the head-to-head in retatrutide's type 2 diabetes programme. Its registration on ClinicalTrials.gov describes a randomised, open-label phase 3 trial in adults whose diabetes was not controlled on metformin, with or without an SGLT2 inhibitor. Participants took weekly retatrutide, which acts on the GIP, GLP-1 and glucagon receptors, or weekly semaglutide. The primary outcome was the change in HbA1c at week 80. The registry lists primary completion as August 27, 2026.
TRANSCEND-T2D-2 at a glance
- What it was: a randomised, open-label phase 3 trial (NCT06260722).
- Who took part: 1,298 adults with type 2 diabetes, HbA1c 7.0% to 10.5% (average 8.3%), average weight 102.4 kg.
- Compared with: semaglutide 2 mg weekly, Ozempic's highest approved dose. There was no placebo group.
- Arms: retatrutide 9 mg, retatrutide 12 mg or semaglutide 2 mg, randomised 2:2:1.
- Length: 80 weeks, with an extension in which about 650 people continue retatrutide for 24 more weeks.
- Published: not yet; the results below are Lilly's own summary.
What Lilly reported
In its October 28 release, the company reported HbA1c falls of 2.2 percentage points on both retatrutide doses against 1.8 on semaglutide. Weight fell 19.5% (20.1 kg) on 9 mg and 20.9% (21.5 kg) on 12 mg, against 9.4% (9.5 kg) on semaglutide. The figures use the efficacy estimand, which describes people who stayed on treatment. The weight differences were statistically significant with the trial's error control. For HbA1c, the 9 mg dose met its non-inferiority test, and its superiority result is only nominal, so it does not count as a confirmed win.
Side effects
The most common side effects were digestive. Diarrhoea was reported by 28.3% and 32.7% on the two retatrutide doses against 26.4% on semaglutide, and vomiting by 10.2% and 15.0% against 13.2%. Dysaesthesia, an abnormal skin sensation seen in earlier retatrutide trials, affected 4.8% and 6.5% against 2.7%. Stopping because of side effects was 4.8% on 9 mg and 7.9% on 12 mg, against 2.7% on semaglutide.
What is not yet known
The release gives no figures for the treatment-regimen estimand, which counts everyone randomised, and no hypoglycaemia rates. The trial was open-label, so participants knew which drug they took. Lilly says the full results will be presented at a medical meeting and published, and names neither. Retatrutide is not approved anywhere, and the release gives no date for a diabetes filing; Lilly's earlier plan is a US submission for obesity in early 2027.
Related on Grey Peptides
The TRIUMPH and TRANSCEND trials, published and topline. Semaglutide encyclopedia entry
The comparator, its approved doses and labels. Retatrutide filing planned for 2027
Lilly's submission plan and its expanded-access programme.
ClinicalTrials.gov - TRANSCEND-T2D-2 (NCT06260722)
Trial design read on ClinicalTrials.gov on November 3, 2026. The results are Eli Lilly's, from its October 28, 2026 announcement, read in full on November 3; they have not been published in a journal or presented at a meeting.