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Retatrutide (LY3437943): Triple GIP/GLP-1/Glucagon Receptor Agonism — Research Overview

Retatrutide (LY3437943) is a synthetic 39-amino-acid peptide engineered as a unimolecular triple agonist acting at the glucose-dependent insulinotropic polypeptide (GIP) receptor, the glucagon-like peptide-1 (GLP-1) receptor, and the glucagon receptor (GCGR). It is a fatty-acid-a

Identity and sequence

Retatrutide (LY3437943) is a synthetic, fatty-acid-acylated 39-residue peptide investigated as a single molecule engaging GIP, GLP-1 and glucagon receptors. This article addresses the retatrutide component of the prepared GLP3 + Cagrilintide blends.

Structural and pharmacological evidence

Li et al. (2024) used structural and signaling experiments to examine retatrutide engagement with GIPR, GLP-1R and GCGR. The work describes shared and receptor-specific contacts and differing activities. Triple agonism does not mean equal or balanced potency at all three receptors.

Primary clinical research as background

Urva et al. (2022) report a phase 1b study in people with type 2 diabetes. Rosenstock et al. (2023) report a phase 2 diabetes trial, and Jastreboff et al. (2023) report a separate phase 2 obesity trial. These controlled clinical studies of the molecule do not validate a catalog blend or supply a research-product administration guide.

Blend and evidence limitations

The 12 mg preparation is labeled retatrutide 10 mg plus cagrilintide 2 mg; the 24 mg preparation is labeled retatrutide 20 mg plus cagrilintide 4 mg. The cited studies do not evaluate those combinations. Retatrutide research cannot be replaced by semaglutide references, and component-level evidence does not establish blend stability, safety or efficacy.

Related

References

  1. Li W et al. (2024). Structural insights into the triple agonism at GLP-1R, GIPR and GCGR manifested by retatrutide. [primary; cryo-EM structures and receptor-signaling experiments]PMID: 39019866DOI: 10.1038/s41421-024-00700-0
  2. Urva S et al. (2022). LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. [primary; human phase 1b diabetes trial]PMID: 36354040DOI: 10.1016/S0140-6736(22)02033-5
  3. Rosenstock J et al. (2023). Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. [primary; human phase 2 diabetes trial]PMID: 37385280DOI: 10.1016/S0140-6736(23)01053-X
  4. Jastreboff AM et al. (2023). Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. [primary; human phase 2 obesity trial]PMID: 37366315DOI: 10.1056/NEJMoa2301972

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