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<p>Obesity is a chronic, relapsing disease driven by complex interactions between genetic, environmental, neuroendocrine and behavioural factors. The advent of incretin-based therapies and the expansion to multi-receptor agonist peptides targeting glucagon-like peptide 1 (GLP1), glucose-dependent insulinotropic polypeptide (GIP), glucagon, and amylin receptors has transformed obesity treatment, demonstrating average weight loss of more than 20% in humans and improvements in a broad range of obesity-related comorbidities. In this Review, we trace the recent evolution of obesity pharmacotherapy from GLP1 receptor agonists to next-generation multi-receptor agonists, alongside strategies that incorporate oral formulations, weight-loss quality approaches and tissue-specific drug targeting. We outline major translational and biological challenges, identify key gaps for future research and discuss emerging approaches aimed at achieving durable and scalable obesity treatment.</p>

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The evolving landscape of obesity pharmacotherapy

  • 期刊论文

  • 发表日期：

    2026年5月13日

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  • Jonas Petersen,
  • Brian Finan,
  • Valdemar B. I. Johansen,
  • Timo D. Müller,
  • Christoffer Clemmensen

摘要

Obesity is a chronic, relapsing disease driven by complex interactions between genetic, environmental, neuroendocrine and behavioural factors. The advent of incretin-based therapies and the expansion to multi-receptor agonist peptides targeting glucagon-like peptide 1 (GLP1), glucose-dependent insulinotropic polypeptide (GIP), glucagon, and amylin receptors has transformed obesity treatment, demonstrating average weight loss of more than 20% in humans and improvements in a broad range of obesity-related comorbidities. In this Review, we trace the recent evolution of obesity pharmacotherapy from GLP1 receptor agonists to next-generation multi-receptor agonists, alongside strategies that incorporate oral formulations, weight-loss quality approaches and tissue-specific drug targeting. We outline major translational and biological challenges, identify key gaps for future research and discuss emerging approaches aimed at achieving durable and scalable obesity treatment.