Tirzepatide: what the SURPASS and SURMOUNT trials showed

Tirzepatide activates both the GIP and GLP-1 receptors. It is FDA-approved as Mounjaro for type 2 diabetes and Zepbound for weight management. The big question it raised was why adding GIP activity helps, since GIP alone was long thought to be a poor drug target. Key papers: 1. Nauck & D'Alessio (Cardiovasc Diabetol, 2022), a review of how the dual mechanism works. https://doi.org/10.1186/s12933-022-01604-7 2. Rosenstock et al. (Lancet, 2021), SURPASS-1, tirzepatide alone in type 2 diabetes. https://doi.org/10.1016/S0140-6736(21)01324-6 3. Jastreboff et al. (NEJM, 2022), SURMOUNT-1, the 72-week obesity trial. https://doi.org/10.1056/NEJMoa2206038 For discussion: how much of the extra effect over semaglutide is GIP, and how much is dose and trial design? The full write-up is in Guides: Tirzepatide.