Remarkably, the fundamental question of whether to agonize or antagonize GIPR to treat obesity remains unanswered given the clinical success of both the dual GLP-1R/GIPR co-agonist tirzepatide [4] and the GIPR antagonist antibody/GLP-1R peptide agonist conjugate maridebart cafraglutide (MariTide, formerly AMG-133) [5]. This evidence concerns the gene GLP1R and obesity due to melanocortin 4 receptor deficiency.