General information with sources. Never a substitute for your doctor.

MethodologyAbout the authorESEN
SaciedadSearch

Randomized controlled trial

TRANSCEND-T2D-1: retatrutide in type 2 diabetes

At 40 weeks, HbA1c fell by 1.69, 1.86 and 1.94 points with retatrutide 4, 9 and 12 mg, compared with 0.81 on placebo; the differences were −0.88 (95% CI, −1.18 to −0.59), −1.04 (95% CI, −1.32 to −0.76) and −1.12 points (95% CI, −1.39 to −0.85).

Bajaj HS et al. Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial. The Lancet, 2026. DOI: 10.1016/S0140-6736(26)00967-0

Prepared by
Last updated
Next review
Sources
2 sources

No clinical review. No advertising from drug companies and no affiliate links.How we work

Key facts

Drug
retatrutide
Design
Randomized controlled trial
Participants
537
Duration
40 weeks
Funding
Eli Lilly
Registry
NCT06354660
Population
537 adults with type 2 diabetes not controlled with diet and exercise alone (HbA1c of 7.0 to 9.5% and BMI of 23 or more), at 48 sites in the United States, Mexico and India; 55% women, mean age 48.8 years, mean HbA1c 7.9%, an average of 2.5 years with diabetes and mean BMI 35.8.
Primary outcome
Change in HbA1c from baseline to week 40 with retatrutide 4, 9 or 12 mg once weekly versus placebo; percentage change in weight was a key secondary objective.

What it found

At 40 weeks, HbA1c fell by 1.69, 1.86 and 1.94 points with retatrutide 4, 9 and 12 mg, compared with 0.81 on placebo; the differences were −0.88 (95% CI, −1.18 to −0.59), −1.04 (95% CI, −1.32 to −0.76) and −1.12 points (95% CI, −1.39 to −0.85). Weight changed by −11.5%, −13.9% and −15.3% with the three doses, compared with −2.6% on placebo. The most common adverse effects were digestive, generally mild or moderate and decreasing over time; between 2 and 5% of participants on retatrutide stopped treatment because of adverse effects, compared with none on placebo. There was no severe hypoglycemia.

Limitations

Funded by Eli Lilly, which is developing retatrutide. It lasted 40 weeks and included only people with short-duration type 2 diabetes who were not taking other diabetes drugs. It was compared with placebo, not with other treatments. Retatrutide is an investigational drug.

What it means for you

In people with short-duration type 2 diabetes who were not taking other diabetes drugs, retatrutide markedly lowered HbA1c and weight over 40 weeks. It is an investigational drug and these data come from a single placebo-controlled trial. They are not a basis for choosing a treatment today.

Further reading

Related trials

  • retatrutide80 weeks

    TRIUMPH-2

    At 80 weeks, weight changed by −11.9%, −16.8% and −18.8% with retatrutide 4, 9 and 12 mg, compared with −5.1% on placebo, using the treatment-regimen estimand.

  • retatrutide80 weeks

    TRIUMPH-1

    At 80 weeks, weight changed by −17.6%, −23.7% and −25.0% with retatrutide 4, 9 and 12 mg, compared with −3.9% on placebo, using the treatment-regimen estimand (intention to treat).

  • retatrutide48 weeks

    Retatrutide phase 2 (obesity)

    In this phase 2 trial, retatrutide (a GIP, GLP-1 and glucagon receptor agonist) reduced weight at 48 weeks by 24.2% with 12 mg once weekly, 22.8% with 8 mg, 17.1% with 4 mg and 8.7% with 1 mg, compared with 2.1% on placebo.

  • orforglipron40 weeks

    ACHIEVE-2

    At 40 weeks, HbA1c fell by 1.23, 1.50 and 1.56 points with orforglipron 3, 12 and 36 mg, compared with 0.81 on dapagliflozin.

Sources

The original paper and the records consulted for this summary, with the date they were accessed.

  1. The Lancet.Bajaj HS, et al. Efficacy and safety of retatrutide in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1). Lancet. 2026;407(10546):2402-2413.accessed .
  2. National Library of Medicine (PubMed).PubMed record PMID 42250575 (abstract).accessed .