TRANSCEND-T2D-1: retatrutide phase 3 monotherapy in early type 2 diabetes

This is the first retatrutide phase 3 result indexed on PubMed as of our check date. It is a diabetes trial, so HbA1c is primary and weight is secondary, but the weight numbers are worth reading against the phase 2 obesity trial.

What the trial asked

Whether retatrutide as monotherapy improves glycaemic control in adults whose type 2 diabetes is inadequately controlled by diet and exercise alone.

Design

Phase 3, randomised 1:1:1:1, double-blind, placebo-controlled, 40 weeks, at 48 sites in the USA, Mexico and India. Once-weekly retatrutide 4 mg, 9 mg or 12 mg versus placebo. Primary endpoint: change in HbA1c from baseline to week 40. Key secondary endpoint: percent change in body weight. The treatment-regimen estimand was primary.

Who was enrolled

930 screened, 537 randomised between April 2024 and April 2025: 134 to 4 mg, 133 to 9 mg, 136 to 12 mg, 134 to placebo. Adults with HbA1c 7.0 to 9.5 percent and BMI of at least 23. Mean age 48.8 (SD 12.1), mean HbA1c 7.9 percent (SD 1.1), mean diabetes duration 2.5 years (SD 4.4), mean BMI 35.8 (SD 7.0); 55 percent female. 490 (91 percent) completed treatment on study drug and 504 (94 percent) completed the study.

Primary endpoint and result

All p less than 0.0001.

Key secondary results

Mean percent change in body weight at week 40: -11.5 percent (SE 0.7) with 4 mg, -13.9 percent (SE 0.8) with 9 mg, -15.3 percent (SE 0.8) with 12 mg, versus -2.6 percent (SE 0.5) with placebo. The abstract does not give confidence intervals or treatment differences for weight.

Adverse events and discontinuation

The most frequent adverse events were gastrointestinal, generally mild to moderate, and subsided over time. Discontinuation of study intervention because of adverse events: 2 to 5 percent with retatrutide, 0 percent with placebo. No severe hypoglycaemia. Two deaths, both in the 4 mg group, unrelated to study drug according to the paper.

Funding and registration

Eli Lilly and Company. ClinicalTrials.gov NCT06354660.

What this trial does not show

• Weight was secondary and the population had recent-onset diabetes with a mean BMI of 35.8. These are not obesity-trial weight numbers and should not be placed beside SURMOUNT or STEP as if they were.
• 40 weeks is shorter than the 48-week phase 2 and much shorter than the 68 to 72 weeks of most obesity trials.
• The comparison is placebo. No arm tells you how retatrutide compares with tirzepatide or semaglutide.
• The obesity phase 3 programme (TRIUMPH) was not indexed on PubMed with results at our check date.

Where the numbers come from

PubMed abstract of the primary paper (PubMed 42250575), fetched 4 September 2026.