Therapeutic Targeting of the GIP Receptor-Revisiting the Controversies

Current and emerging strategies to therapeutically target weight management include pairing agonism of the glucagon-like peptide 1 receptor (GLP-1R) with either agonism or antagonism of the glucose-dependent insulinotropic polypeptide receptor (GIPR). On the surface, these two approaches seem contradictory, yet they have produced similar effects for weight loss in clinical studies. Arguments that support the rationale for both approaches are made in these point-counterpoint articles, founded on preclinical studies, human genetics, and clinical outcomes. Here, we attempt to reconcile how two opposing approaches can produce similar effects on body weight by evaluating the leading hypotheses derived from the available evidence.