Critical analysis of GPCRs implicated in metabolic disease reveals that, despite apparent selectivity at the level of ligand binding, few receptors prove exquisitely specific when subjected to exhaustive pharmacological analysis in cellular and animal models. This review has highlighted several targets with demonstrated potential for therapeutic intervention, by virtue of medical need and tractability. Ultimate success, as measured by amelioration of human maladies, will depend upon the ability of the scientific community to elucidate mechanisms of action and further augment understanding of the molecular basis and promise of targeting GPCRs for the treatment of disease.

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