Glucagon-like peptide 1 in the pathophysiology and pharmacotherapy of clinical obesity

Core Tip

Core tip: Several lines of clinical evidence implicate an important functional role for glucagon-like peptide 1 (GLP-1) signalling in the pathophysiology of clinical obesity. Here we critically evaluate such findings in way that as yet has been unexplored; using the well established roles of GLP-1 as an incretin and meal to meal satiety signal to go some way toward explaining findings from interventional and observational clinical data that suggest functional deficits of GLP-1 to be a contributor to the obesity phenotype. We also explore the promise shown by GLP-1 analogues in achieving and maintaining significant weight loss in obese individuals, and use findings to discuss to what extent they too may support a role for GLP-1 in obesity pathophysiology. We conclude by exploring what an association with functional GLP-1 deficit could mean for the clinical management of obesity; conducting cost and risk benefit analyses to evaluate the extent to which GLP-1 analogues may provide a successful and sustainable option for the medical management of obesity that remains as yet, an unmet clinical need.