Laboratory of Morphometry, Metabolism and Cardiovascular Diseases, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
Laboratory of Morphometry, Metabolism and Cardiovascular Diseases, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
Life Sci. 2022 Jan 1;288:120188. doi: 10.1016/j.lfs.2021.120188. Epub 2021 Nov 30.
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.
最近,治疗 2 型糖尿病(T2DM)的治疗手段得到了丰富,包括了 1 型胰高血糖素样肽(GLP-1)。GLP-1 受体激动剂(RA)可间接降低食欲、减缓胃排空并减轻体重。这种作用已被用于治疗超重/肥胖症,尤其是与 T2DM 相关的合并症。然而,最初的制剂和不良反应逐渐被新的制剂所取代,这些新制剂的不良反应更少,作用时间更长(每周皮下注射,甚至口服),从而提高了患者对治疗的接受度和依从性。因此,GLP-1RA 的滴定应逐渐进行。此外,在经过数周/数月的滴定后,如果不良反应持续且无法耐受,应降低剂量或联合使用其他降糖治疗方案,避免中断治疗。制药行业不断努力研发出更有效、副作用更少的分子,这是推动药物研发的动力。具有单分子双重激动作用的 GLP-1RA 加胰高血糖素受体激动剂(GRA)代表了一种更新的治疗 2 型糖尿病及其合并症的药理学指标,与单 GLP-1RA 相比,它具有更好的疗效和更少的不良反应。目前,不同实验室都提出了不同的方案。然而,实验结果很有前景,表明很快我们将有新的药物来治疗 T2DM。