Retatrutide

Retatrutide is a triple receptor agonist. It acts at the GIP receptor, the GLP-1 receptor, and the glucagon (GCG) receptor.

The development code is LY3437943. Eli Lilly develops it. It is one peptide with a fatty diacid group. It is investigational.

Retatrutide acts at three receptors. The added glucagon agonism can increase energy expenditure. It can also decrease food intake.

Evidence tier: clinical, Phase 2.

A Phase 2 trial randomized participants to seven arms. The 12 mg dose gave a mean weight decrease of 24.2% at 48 weeks. The weight curves did not reach a plateau at that point.

A Phase 2a substudy in MASLD enrolled 98 participants. Liver fat decreased by up to 82.4%.

Evidence limit. No Phase 3 result and no approval exist yet.

Phase 2 used 1 mg, 4 mg, 8 mg, and 12 mg by subcutaneous injection, once each week, after an initial step increase.

No approved label exists. These are trial doses under trial supervision. They are not a recommendation.

The trials used one subcutaneous dose each week.

Researchers expect the class effects of an incretin agonist. These are delayed gastric emptying and a low blood glucose risk with insulin or a sulfonylurea.

No formal interaction study exists yet.

Compare with Tirzepatide and Semaglutide.

The most common adverse events in Phase 2 were gastrointestinal. They increased with the dose. No participant stopped the trial because of them.

• HbA1c and glucose.
• Liver fat and liver enzymes.

No regulator approves retatrutide. The Phase 3 TRIUMPH program continues.

WADA prohibits a non-approved substance under S0. See the WADA prohibited list status.