Retatrutide: the triple agonist and the Phase 2 results

Retatrutide (LY3437943) acts on three receptors: GLP-1, GIP and glucagon. It is investigational and not approved anywhere. The idea behind the glucagon arm is to add energy expenditure on top of the appetite effects. Key papers: 1. Coskun et al. (Cell Metab, 2022), the preclinical and early human pharmacology. https://doi.org/10.1016/j.cmet.2022.07.013 2. Jastreboff et al. (NEJM, 2023), the 48-week Phase 2 obesity trial. https://doi.org/10.1056/NEJMoa2301972 3. Melson et al. (Int J Obes, 2024), on where it sits in the pipeline of upcoming obesity drugs. https://doi.org/10.1038/s41366-024-01473-y Phase 3 trials are underway. If you've seen published Phase 3 results, post the link. For discussion: what does the glucagon arm add, and what are the trade-offs, such as heart rate? The full write-up is in Guides: Retatrutide.