GIPR–GLP-1R coagonists such as TZP are now approved for T2D and obesity, retatrutide — the GIPR-biased triple agonist— is in phase 3 clinical trials (41) and the GIPR antagonist-GLP-1RA, AMG-133, is also being studied in phase 2/3 trials (2, 4); therefore, understanding how gain and loss of GIPR signaling in different tissue compartments modifies the response to gut injury may have translational relevance. This evidence concerns the gene GLP1R and obesity due to melanocortin 4 receptor deficiency.