Novel approaches to anti-obesity drug discovery with gut hormones over the past 10 years.

Frances Rose, Stephen Bloom, Tricia Tan

Expert opinion on drug discovery 2019 Nov

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Introduction: Obesity is a global pandemic and new pharmacotherapies which combine weight loss efficacy, long-term safety, and reversal of metabolic co-morbidities are sorely needed. Gut hormones play key roles in regulating satiety and metabolism, and are natural candidates for therapeutic development. Areas covered: The authors discuss recent drug developments for the treatment of obesity using gut hormones. The review was based on a search of PubMed using keywords 'obesity' AND ('therapy' OR 'pharmacotherapy' OR 'gut hormones' OR 'analogues'), limited to the last 10 years. Expert opinion: Analogues of glucagon-like peptide (GLP-1) have been developed for obesity but so far do not provide enough weight loss. Bariatric surgery increases the post-prandial secretion of multiple gut hormones, leading to beneficial effects on weight loss and metabolism. This recognition has led to poly-agonist strategies: GLP-1/glucagon or GLP-1/glucose-dependent insulinotropic peptide (GIP) dual agonism, or even GLP-1/glucagon/GIP triple agonism. New delivery approaches include peptide-conjugate therapies that target key metabolic tissues. Practicable methods for oral delivery of peptide gut hormones are also close to market, expanding the potential market for these treatments. Anti-obesity therapy is therefore poised for an exciting phase, and it will be interesting to see which of these will eventually prevail.

Citation

Frances Rose, Stephen Bloom, Tricia Tan. Novel approaches to anti-obesity drug discovery with gut hormones over the past 10 years. Expert opinion on drug discovery. 2019 Nov;14(11):1151-1159