Another mechanistic pathway postulated recently by Gasbjerg and colleagues is that tirzepatide acts solely as a GLP-1R super agonist (Gasbjerg et al. 2023b), but this possibility seems less appealing based on the more impressive effects of tirzepatide over those of GLP-1 mimetics in both humans and animal models with obesity-diabetes (Coskun et al. 2018, Frias et al. 2020b). Here, GLP1R is linked to obesity due to melanocortin 4 receptor deficiency.