4.7 Article

The current significance and prospects for the use of dual receptor agonism GLP-1/Glucagon

Journal

LIFE SCIENCES
Volume 288, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2021.120188

Keywords

Type 1 glucagon-like peptide; Type 2 diabetes mellitus; Overweight; Obesity; Oxyntomodulin

Funding

  1. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (Brazil) (CNPq) [302.920/2016-1, 40.60.81/2018-2]
  2. Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (Faperj) [E-26/010.001274/2016, E-26/010.100947/2018, E-26/200.936/2021]
  3. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brazil (CAPES) [001]

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The therapeutic arsenal for treating type 2 diabetes has recently been enriched with the inclusion of GLP-1 receptor agonists, which secondarily reduce appetite, decrease gastric emptying, and reduce body weight. New formulations with fewer adverse effects and extended action periods have improved treatment acceptance and adherence. The pharmaceutical industry's efforts to produce more powerful molecules with fewer side effects will soon lead to the introduction of new drugs for the treatment of type 2 diabetes.
The therapeutic arsenal for treating type 2 diabetes mellitus (T2DM) has been enriched recently with the inclusion of type 1 glucagon-like peptide (GLP-1). GLP-1 receptor agonists (RA) secondarily reduce appetite, decrease gastric emptying, and reduce body weight. This effect has been used to treat overweight/obesity, especially with comorbidities associated with T2DM. However, the first formulations and adverse effects gradually gave way to new formulations with fewer unpleasant effects and a more extended period of action (weekly subcutaneous administration and even oral administration), which improved the acceptance and adherence to the treatment. Therefore, titration of GLP-1RA should be done gradually. Furthermore, when side effects are consistent and intolerable after weeks/months of titration, a lower dose or a combination of antidiabetic therapies should be implemented, avoiding treatment interruption. The effort to produce increasingly powerful molecules with fewer side effects is the driving force behind the pharmaceutical industry. The unimolecular dual agonism GLP-1RA plus glucagon receptor agonism (GRA) represents an updated pharmacological indication for controlling blood glucose levels in treating T2DM and its comorbidities, showing better effects with less adverse impact than mono GLP-1RA. There are currently different proposals in this way by different laboratories. Nevertheless, the experimental results are promising and show that soon, we will have the contribution of new drugs for the treatment of T2DM.

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