SGLT2抑制剂在糖尿病管理中的作用:关注HbA1c水平、体重减轻和遗传变异

P. Kaur, Sushil Kotru, Leena Tuteja, Abhilash Ludhiadch, A. Munshi
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引用次数: 0

摘要

葡萄糖共转运体-2 (SGLT2)抑制剂是最近加入到2型糖尿病(T2DM)治疗策略中的药物。这是一种非胰岛素依赖的抗糖尿病治疗方法,通过排尿消除血浆葡萄糖。该研究的目的是评估SGLT2抑制剂对有反应和无反应患者的HbA1c水平和体重减轻的影响。此外,在研究人群中评估了SLC5A2 (rs9934336)和UGT1A9 (rs72551330)这两个重要变异对SGLT2抑制剂应答的个体间差异的影响。该研究纳入了200名接受SGLT2抑制剂治疗的确诊T2DM患者。HbA1c水平和体重下降的患者被归类为反应者,而治疗后这两个参数未显着下降的患者被归类为无反应者。评估有反应者和无反应者治疗前后HbA1c水平与体重减轻的关系。Sanger测序筛选了影响SGLT2抑制剂应答的两个显著变异SLC5A2 (rs9934336)和UGT1A9 (rs72551330)。治疗前后,有反应者和无反应者的HbA1c水平和体重有显著差异。然而,没有发现SLC5A2 (rs9934336)和UGT1A9 (rs72551330)这两种变体与药物反应有显著相关性。总之,SGLT2抑制剂有效降低了应答者的HbA1c水平和体重。然而,在给旁遮普Malwa地区的2型糖尿病患者开这类药物之前,不需要对目标基因变异进行基因检测。重点:葡萄糖共转运蛋白-2 (SGLT2)抑制剂治疗2型糖尿病(T2DM)是一种不依赖胰岛素的方法,通过降低肾小管葡萄糖重吸收来降低血糖水平。在SGLT2抑制剂治疗后,观察到应答者的HbA1c水平显著下降,体重减轻。研究人员对两个基因变异SLC5A2 (rs9934336)和UGT1A9 (rs72551330)进行了药理学分析,这两个基因变异与SGLT2抑制剂的个体间反应有关。所有测试的变异均未发现与个体间对SGLT2抑制剂的反应显著相关。旁遮普Malwa地区使用SGLT2抑制剂的T2DM患者不需要对两种最常见的变异进行药物遗传学检测。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Role of SGLT2 Inhibitors in Diabetes Management: Focus on HbA1c Levels, Weight Loss and Genetic Variation
Sodium Glucose Co-transporters-2 (SGLT2) inhibitors are the recent addition to treatment strategies for Type 2 Diabetes Mellitus (T2DM). It is a non-insulin dependent anti-diabetic therapeutic approach that eliminates plasma glucose by urination. The study was carried out with the aim of evaluating the effect of SGLT2 inhibitors on HbA1c levels and weight loss in responders and non-responders. In addition, the role of two significant variants, SLC5A2 (rs9934336) and UGT1A9 (rs72551330), affecting the inter-individual variation in response to SGLT2 inhibitors was evaluated in the study population. 200 confirmed T2DM patients on SGLT2 inhibitors were enrolled for the study. Patients with decreased HbA1c levels and body weight were categorized as responders, whereas the ones who did not show a significant decrease in these two parameters after treatment were categorised as non-responders. Association of HbA1c levels and weight loss before as well as after treatment with responders and non-responders was evaluated. Patients were screened for two significant variants, SLC5A2 (rs9934336) and UGT1A9 (rs72551330), affecting the inter-individual variation in response to SGLT2 inhibitors by Sanger Sequencing. A significant difference in HbA1c levels and weight was found in responders and non-responders before and after the treatment. However, both of the variants, SLC5A2 (rs9934336) and UGT1A9 (rs72551330), were not found to be significantly associated with the drug response. In conclusion, SGLT2 inhibitors reduced HbA1c levels and weight effectively in responders. However, the targeted gene variants need not to be involved in genetic testing before prescribing this class of drugs to T2DM patients from Malwa region of Punjab. Highlights: Treatment of Type 2 diabetes mellitus (T2DM) with Sodium Glucose co-transporter-2 (SGLT2) inhibitors is an insulin-independent method of reducing blood glucose levels by lowering renal tubular glucose reabsorption. Significant decrease in HbA1c levels and weight loss in responders was observed after the treatment with SGLT2 inhibitors. Pharmacogenetic analysis was carried out for two gene variants, SLC5A2 (rs9934336) and UGT1A9 (rs72551330), reported to be involved in inter-individual response to SGLT2 inhibitors. None of the tested variants were found to be significantly associated with inter-individual response to SGLT2 inhibitors. Pharmacogenetic testing for the two most commonly reported variants is not required for the T2DM patients on SGLT2 inhibitors from the Malwa region of Punjab.
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