Retatrutide

An investigational triple agonist at the GIP, GLP-1 and glucagon receptors that produced the largest weight reductions yet reported in a phase 2 obesity trial.

What it is

Retatrutide is a single engineered peptide that activates three receptors: GIP, GLP-1 and glucagon. The first two are familiar from tirzepatide. Adding glucagon receptor activity is the novel part, because glucagon increases energy expenditure and mobilizes liver fat, which is a different lever from appetite suppression.

What phase 2 showed

In a randomized phase 2 trial published in 2023, adults with obesity receiving the highest dose lost an average of roughly 24 percent of body weight at 48 weeks, with the curve still declining at the end of the study. Those are the largest reductions reported for a pharmacological agent to date.

Phase 3 trials are ongoing. Phase 2 results have repeatedly failed to hold up at phase 3 scale in metabolic medicine, and long term safety in a broad population is exactly what phase 3 exists to establish.

Availability and the compounding question

Retatrutide is not approved by the FDA and is not legitimately available for patient care. It is not a candidate for compounding either, because compounding law is built around approved active ingredients, and material sold online under this name is research chemical supply.

Baseline covers retatrutide as education only. When and if it is approved, that changes.

Baseline does not dispense retatrutide, and would not before approval. This entry exists so the comparison to what is available is honest.

References

  1. Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial. N Engl J Med. 2023.
  2. Coskun T, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist. Cell Metab. 2022.