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新型抗糖尿病药物的药物遗传学。

Pharmacogenetics of new classes of antidiabetic drugs.

机构信息

Department of Biochemistry and Clinical Analysis, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina.

Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Sarajevo, Sarajevo, Bosnia and Herzegovina.

出版信息

Bosn J Basic Med Sci. 2021 Dec 1;21(6):659-671. doi: 10.17305/bjbms.2021.5646.

Abstract

Type 2 diabetes (T2D) has a continuously rising prevalence worldwide. Pharmacogenetics has been recognized as a promising concept for pharmacological treatment of T2D, as antidiabetic drugs are not equally effective and safe for all patients, and the costs of diabetes treatment are increasing. The latest published guidelines on T2D treatment firmly endorse the use of newer antidiabetic drugs, sodium-glucose cotransporter-2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP-IVi), and glucagon-like peptide-1 receptor agonists (GLP-1RA), considering their satisfactory pharmacological effect and good safety profile. Furthermore, SGLT2i and GLP-1RA show protective effects in patients with established atherosclerotic cardiovascular disease and chronic kidney disease. However, there has been growing evidence that the effectiveness and safety of these drug classes could depend on genetic variability. Here, we summarized the results of the published studies on the pharmacogenetic biomarkers for the three drug classes. A number of genetic variations have been investigated so far. The explored candidate genes mostly encode drug targets, drug-metabolizing enzymes, and genes linked to T2D risk. Although many of the results are promising, it is still necessary to obtain more information from larger controlled studies to confirm their clinical significance. This approach may lead towards more personalized treatment for patients with T2D.

摘要

2 型糖尿病(T2D)在全球范围内的患病率持续上升。药物遗传学已被认为是治疗 T2D 的一种有前途的概念,因为抗糖尿病药物对所有患者的疗效和安全性并不相同,而且糖尿病治疗的成本正在不断增加。最新发布的 T2D 治疗指南坚决支持使用新型抗糖尿病药物,即钠-葡萄糖共转运蛋白 2 抑制剂(SGLT2i)、二肽基肽酶-4 抑制剂(DPP-IVi)和胰高血糖素样肽-1 受体激动剂(GLP-1RA),因为它们具有令人满意的药理作用和良好的安全性。此外,SGLT2i 和 GLP-1RA 在已确诊的动脉粥样硬化性心血管疾病和慢性肾脏病患者中具有保护作用。然而,越来越多的证据表明,这些药物类别的有效性和安全性可能取决于遗传变异性。在这里,我们总结了已发表的关于这三类药物的药物遗传学生物标志物的研究结果。到目前为止,已经研究了许多遗传变异。探索的候选基因主要编码药物靶点、药物代谢酶和与 T2D 风险相关的基因。尽管许多研究结果很有希望,但仍需要从更大的对照研究中获得更多信息来确认其临床意义。这种方法可能会为 T2D 患者提供更个性化的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4de0/8554705/58e7e3162b8e/BJBMS-21-659-g001.jpg

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