Taken together, the increased effect of simultaneous GIPR and GLP-1R agonism relative to GLP-1R monoagonism on AgRP neuron dynamics aligns with mounting evidence for the superior efficacy of combined GIP and GLP-1R activation for the treatment of obesity (25–28), and may represent a partial mechanism for the remarkable weight loss induced by dual incretin agonism. This evidence concerns the gene GLP1R and obesity due to melanocortin 4 receptor deficiency.