Anastasiou, Ioanna ? (I?);Argyrakopoulou, Georgia (G);Dalamaga, Maria (M);Kokkinos, Alexander (A);

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Curr Obes Rep.2025 Apr 11;14(1):34.doi:10.1007/s13679-025-00623-1

Abstract

PURPOSE OF REVIEW: The development of long-acting incretin receptor agonists represents a significant advance in the fight against the concurrent epidemics of type 2 diabetes mellitus (T2DM) and obesity. The aim of the present review is to examine the cellular processes underlying the actions of these new, highly significant classes of peptide receptor agonists. We further explore the potential actions of multi-agonist drugs as well as the mechanisms through which gut-brain communication can be used to achieve long-term weight loss without negative side effects.

RECENT FINDINGS: Several unimolecular dual-receptor agonists have shown promising clinical efficacy studies when used alone or in conjunction with approved glucose-lowering medications. We also describe the development of incretin-based pharmacotherapy, starting with exendin- 4 and ending with the identification of multi-incretin hormone receptor agonists, which appear to be the next major step in the fight against T2DM and obesity. We discuss the multi-agonists currently in clinical trials and how each new generation of these drugs improves their effectiveness. Since most glucose-dependent insulinotropic polypeptide (GIP) receptor: glucagon-like peptide- 1 receptor (GLP- 1) receptor: glucagon receptor triagonists compete in efficacy with bariatric surgery, the success of these agents in preclinical models and clinical trials suggests a bright future for multi-agonists in the treatment of metabolic diseases. To fully understand how these treatments affect body weight, further research is needed.