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Randomized controlled trial

Retatrutide phase 2 trial in obesity: results at 48 weeks

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.

Jastreboff AM et al. Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. New England Journal of Medicine, 2023. DOI: 10.1056/NEJMoa2301972

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Key facts

Drug
retatrutide
Design
Randomized controlled trial
Participants
338
Duration
48 weeks
Funding
Eli Lilly
Registry
NCT04881760
Population
338 adults with a BMI of 30 or more (or 27 to 30 with at least one weight-related condition), without diabetes.
Primary outcome
Percentage change in body weight at 24 weeks; the change at 48 weeks was a secondary objective.

What it found

Mean weight loss, % of starting weight · 48 weeks
  • Retatrutide 1 mg weekly−8.7%
  • Retatrutide 4 mg weekly−17.1%
  • Retatrutide 8 mg weekly−22.8%
  • Retatrutide 12 mg weekly−24.2%
  • Placebo−2.1%

Difference (Retatrutide 1 mg weekly): −6.6 points vs placebo (subtraction).

Difference (Retatrutide 4 mg weekly): −15.0 points vs placebo (subtraction).

Difference (Retatrutide 8 mg weekly): −20.7 points vs placebo (subtraction).

Difference (Retatrutide 12 mg weekly): −22.1 points vs placebo (subtraction).

Figures from the paperSee the results in a chart

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. At 24 weeks (the primary outcome), the reduction was 17.5% with 12 mg versus 1.6% on placebo. The most common adverse effects were digestive and dose-dependent. Confidence intervals are not given in the paper’s abstract.

Limitations

A phase 2 trial with few participants per group, funded by Eli Lilly; phase 3 results (the TRIUMPH program) have been announced in press releases but had not been published in a peer-reviewed journal as of the review date. The drug is not approved in any country.

What it means for you

This phase 2 trial showed very large weight losses with retatrutide, but with few participants per group and over 48 weeks. Retatrutide is an investigational drug. The full phase 3 results are needed to know whether the figures hold up and with what safety profile.

Further reading

Related trials

  • retatrutide40 weeks

    TRANSCEND-T2D-1

    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.

  • orforglipron52 weeks

    ATTAIN-MAINTAIN

    On orforglipron, 74.7% of the weight lost on tirzepatide was maintained, versus 49.2% on placebo.

  • tirzepatide112 weeks

    SURMOUNT-MAINTAIN

    At week 112, weight had changed by −21.9% on the maximum tolerated dose of tirzepatide, −16.6% on 5 mg and −9.9% on placebo.

  • orforglipron72 weeks

    ATTAIN-1

    Orforglipron, an oral small-molecule GLP-1 receptor agonist, reduced weight at 72 weeks by 11.2% with 36 mg, 8.4% with 12 mg and 7.5% with 6 mg, compared with 2.1% on placebo.

Sources

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

  1. New England Journal of Medicine.Jastreboff AM, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. N Engl J Med. 2023;389(6):514-526.accessed .
  2. National Library of Medicine (PubMed).PubMed record PMID 37366315 (abstract).accessed .