By comparing the metabolic effects of a pair of matched peptides with these sequence substitutions, we demonstrate that reduced recruitment efficacy of β-arrestins translates into improved efficacy in preclinical rodent models of obesity, consistent with a similar effect previously observed for GLP-1R mono-agonists [[18], [19], [20], [21]]. The gene discussed is GLP1R; the disease is obesity due to melanocortin 4 receptor deficiency.