Pharmacotherapy for chronic obesity management: a look into the future

Mariana Abdel-Malek, Lisa Yang, Alexander Dimitri Miras

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Substantial leaps have been made in the drug discovery front in tackling the growing pandemic of obesity and its metabolic co-morbidities. Greater mechanistic insight and understanding of the gut-brain molecular pathways at play have enabled the pursuit of novel therapeutic agents that possess increasingly efficacious weight-lowering potential whilst remaining safe and tolerable for clinical use. In the wake of glucagon-like peptide 1 (GLP-1) based therapy, we look at recent advances in gut hormone biology that have fermented the development of next generation pharmacotherapy in diabesity that harness synergistic potential. In this paper, we review the latest data from the SURPASS and SURMOUNT clinical trials for the novel 'twincretin', known as Tirzepatide, which has demonstrated sizeable body weight reduction as well as glycaemic efficacy. We also provide an overview of amylin-based combination strategies and other emerging therapies in the pipeline that are similarly providing great promise for the future of chronic management of obesity.
Original languageEnglish
Pages (from-to)1019-1030
Number of pages12
JournalInternal and Emergency Medicine
Issue number4
Early online date30 May 2023
Publication statusPublished online - 30 May 2023

Bibliographical note

Funding Information:
The views expressed in this manuscript are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The Section of Endocrinology and Investigative Medicine is funded by grants from the MRC, BBSRC, NIHR and is supported by the NIHR Biomedical Research Centre Funding Scheme. Prof Alex Miras has also received research funding from the MRC, NIHR, Jon Moulton Charity Trust, Fractyl, Novo Nordisk and Randox.

Publisher Copyright:
© 2023, Crown.


  • Amylin
  • Tirzepatide
  • Obesity
  • Glucagon-like peptide 1
  • Type 2 diabetes
  • Glucagon dependent insulinotropic polypeptide


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