Initial reports that GIPR null mice [64] are protected from diet-induced obesity have been supported by preclinical studies in rodents and non-human primates that GIPR antagonism induces additive weight loss when combined with GLP-1R agonism [32,67], and human genetics data that loss-of-function GIPR variants associate with reduced adiposity [68]. Here, GLP1R is linked to obesity due to melanocortin 4 receptor deficiency.