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Type 2 diabetes (T2D) is a major healthcare concern.G-protein-coupled receptor (GPCR) ligands are used to treat a range of diseases.Human islets express nearly three hundred GPCRs.Only one islet GPCR is currently the target of a clinically used T2D therapy.Pharmaceutical companies are developing T2D therapies that activate islet GPCRs.The incidence of type 2 diabetes (T2D) is increasing at an alarming rate, which is imposing substantial healthcare and economic burdens worldwide. T2D can be treated by a range of drugs, but there is a need to identify additional therapeutic options. Human islets express nearly three hundred G-protein-coupled receptors (GPCRs), which could be targeted for the treatment of T2D. However, to date, the GLP-1 receptor is the only islet GPCR for which agonists are in current clinical use. This review explores pharmaceutical development of drugs that activate individual or multiple β-cell GPCRs and explains how our knowledge of GPCR expression by human islets may inform direction on novel GPCR targets.