Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Cell. 2024 Jul 25;187(15):3829-3853. doi: 10.1016/j.cell.2024.06.003.
For more than a century, physicians have searched for ways to pharmacologically reduce excess body fat. The tide has finally turned with recent advances in biochemically engineered agonists for the receptor of glucagon-like peptide-1 (GLP-1) and their use in GLP-1-based polyagonists. These polyagonists reduce body weight through complementary pharmacology by incorporating the receptors for glucagon and/or the glucose-dependent insulinotropic polypeptide (GIP). In their most advanced forms, gut-hormone polyagonists achieve an unprecedented weight reduction of up to ∼20%-30%, offering a pharmacological alternative to bariatric surgery. Along with favorable effects on glycemia, fatty liver, and kidney disease, they also offer beneficial effects on the cardiovascular system and adipose tissue. These new interventions, therefore, hold great promise for the future of anti-obesity medications.
一个多世纪以来，医生们一直在寻找药理学方法来减少多余的体脂肪。随着最近在胰高血糖素样肽-1 (GLP-1) 受体的生化工程激动剂方面的进展，以及它们在基于 GLP-1 的多激动剂中的应用，这一趋势终于发生了转变。这些多激动剂通过结合胰高血糖素和/或葡萄糖依赖性胰岛素释放多肽 (GIP) 的受体，通过互补的药理学来减轻体重。在其最先进的形式中，肠激素多激动剂实现了高达约 20%-30%的前所未有的体重减轻，为减重手术提供了一种药理学替代方案。除了对血糖、脂肪肝和肾脏疾病有有利影响外，它们还对心血管系统和脂肪组织有有益影响。因此，这些新的干预措施为未来的抗肥胖药物带来了巨大的希望。
