小分子钠-葡萄糖协同转运蛋白2抑制剂的研究进展

慢性高血糖是2型糖尿病(T2DM)的主要特征。钠-葡萄糖协同转运蛋白2(sodium-glucose cotransporter 2,SGLT2)是位于肾脏上的一种转运蛋白,它可以介导原尿中葡萄糖的重吸收,对维持人体血糖平衡起着关键性的作用。SGLT2抑制剂可以在近曲小管减少肾对葡萄糖的重吸收,增加尿液中葡萄糖的排泄量,从而降低血糖。本文就不同类型的SGLT2抑制剂的研究进展进行综述。     

治疗糖尿病新药:钠-葡萄糖协同转运蛋白抑制剂dapagliflozin

钠-葡萄糖协同转运蛋白2(SGLT-2)是一种跨膜蛋白,主要分布在肾脏近曲小管,将葡萄糖从肾小管液转运入肾小管细胞内,约占肾脏重吸收葡萄糖的90%。SGLT-2抑制剂是治疗糖尿病的新药,可降低SGLT-2活性,减少肾脏对葡萄糖的重吸收量,增加尿糖排出,从而降低血糖。已有的临床试验表明SGLT-2抑制剂dapagliflozin治疗糖尿病有效且安全,患者耐受性良好。SGLT-2抑制剂很可能是未来糖尿病治疗的一个新的突破口。     

钠-葡萄糖协同转运蛋白2抑制剂在2型糖尿病合并高血压患者中应用的研究进展

近年来糖尿病发病率显著升高,尤其是2型糖尿病(T2DM).T2DM与高血压的发生发展密切相关,T2 DM合并高血压可对患者心、脑、肾等靶器官造成损害.因此,合理有效地控制T2 DM患者的血压水平至关重要.钠-葡萄糖协同转运蛋白2(SGLT-2)抑制剂作为一种新型降糖药,除具有降糖作用外,还具有心、肾保护等作用.本文对S...     

2型糖尿病治疗靶点钠-葡萄糖共转运蛋白2抑制剂研究进展

钠-葡萄糖共转运蛋白2(sodium-glucose co-transporter 2,SGLT-2)分布在肾脏近曲小管S1部位,负责肾脏中约90%葡萄糖的重吸收,抑制SGLT-2可以促进糖尿病患者尿糖的排出,因此SGLT-2抑制剂被认为是一种新型的具有独特作用机制的抗糖尿病药物。本文按照化合物的结构特征分类,重点介绍O-芳基糖苷类、C-芳基糖苷类、O,C-螺环芳基糖苷类、N-芳基糖苷类以及非糖苷类SGLT-2抑制剂的构效关系以及最新研究进展。     

钠-葡萄糖协同转运蛋白抑制剂治疗心力衰竭的研究进展

钠-葡萄糖协同转运蛋白2抑制剂(SGLT2i)是一类新型口服降糖药.大量临床研究表明:SGLT2i可通过非胰岛素依赖机制降低心血管疾病病死率和心力衰竭住院率,有望成为心力衰竭治疗的基础药物之一.本综述总结了SGLT2i治疗心力衰竭的潜在机制和相关临床研究进展.     

钠-葡萄糖协同转运蛋白2抑制剂降低新发房颤潜在机制研究

房颤作为最常见的心律失常,可以单独也可以继发于其他心血管疾病。心房肌细胞离子通道、线粒体功能、能量守恒等的紊乱是房性心律失常发生和维持的细胞机制。钠-葡萄糖协同转运蛋白2抑制剂作为新型降糖药而非抗心律失常药,不仅对心力衰竭有积极影响,还能调节离子通道平衡、改善线粒体功能、维持能量平衡、缓解心房结构重塑,从而潜在地降低新发房颤的发生率。本文对钠-葡萄糖协同转运蛋白2抑制剂降低新发房颤潜在机制进行综述。     

钠-葡萄糖协同转运蛋白-2抑制剂致不良反应分析

目的 探讨钠-葡萄糖协同转运蛋白-2(SGLT-2)抑制剂在临床使用中药品不良反应发生的规律及特点,以提高临床用药安全.方法 检索中国知网、万方数据、维普网、PubMed、Embase、Medline数据库,对建库以来至2019年11月28日国内外公开发表的有关SGLT-2抑制剂致药品不良反应病例文献报道进行回顾性分析...     

钠-葡萄糖协同转运蛋白2抑制药抗心力衰竭研究进展

钠-葡萄糖协同转运蛋白2(SGLT2)抑制药是一种新型降糖药,已广泛应用于临床.近年来发现SGLT2抑制药不仅可以降低血糖,还可以改善心力衰竭及其危险因素,也会引起血糖正常的酮症酸中毒等不良反应.阐明SGLT2抑制药抗心力衰竭的作用机制对临床合理用药意义重大,近期研究发现SGLT2抑制药可以通过调节线粒体功能、调节钠稳...     

新型降血糖药物钠-葡萄糖共转运蛋白2抑制剂

钠-葡萄糖共转运蛋白2(sodium-glucose cotransporter 2,SGLT2)抑制剂是一类新型降血糖药物,能直接促进肾脏对葡萄糖的排泄.SGLT2抑制剂除具有降血糖作用外,还有一些有益的降血糖外效应.这些降血糖外效应已受到人们的重视,并得到临床应用.本文概要介绍SGLT2抑制剂的作用机制、临床益处和...     

钠-葡萄糖共转运蛋白2抑制剂在高血压治疗中的研究进展

随着钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂用于2型糖尿病的治疗,及其在预防心血管事件方面的疗效,其降血压作用受到关注。本文就SGLT-2抑制剂降低高血压的主要作用机制、相关临床试验、不良反应,以及该药物目前存在的问题及未来的研究方向进行综述。     

Differentiating sodium-glucose co-transporter-2 inhibitors in development for the treatment of type 2 diabetes mellitus

Introduction: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are a novel class of agents for the treatment of type 2 diabetes mellitus (T2DM). By inhibiting SGLT2, they prevent renal glucose reabsorption, resulting in glucosuria.

Areas covered: The rationale for development of SGLT2 inhibitors is reviewed, with particular focus on the nine SGLT2 inhibitors currently in development. The authors compare the potency and SGLT2 selectivity of the agents, as well as the results from both animal and clinical studies, considering the potential implications they may have for clinical use.

Expert opinion: Current evidence suggests that SGLT2 inhibitors have similar efficacy in terms of glycemic control and also demonstrate benefits beyond glycemic reductions, including reductions in body weight and modest reductions in blood pressure. Additionally, they appear to preserve beta-cell function and improve insulin sensitivity. Their mechanism of action allows for combination of SGLT2 inhibitors with other antidiabetic drugs and use across the treatment continuum for T2DM. Potential differences in safety and efficacy based on observed differences in potency and selectivity among the SGLT2 inhibitors, particularly versus SGLT1, remain to be seen. Further long-term data, including post-marketing surveillance, are required to fully determine the safety profile of SGLT2 inhibitors in large patient groups.     

SGLT2抑制剂治疗糖尿病研究进展

近年来,钠-葡萄糖协同转运蛋白2(type 2 sodium glucose co-transporters,SGLT2)抑制剂作为一种新型的治疗糖尿病药物成为研究热点。SGLT2在肾近端小管葡萄糖重吸收中起着非常重要的作用;抑制肾脏SGLT2可以促进Ⅱ型糖尿病人尿糖的排泄,使其血糖恢复正常而不会有低血糖的风险。临床实验表明,SGLT2抑制剂对Ⅱ型糖尿病的治疗效果明显,且具有降低体重、无低血糖风险等优点,目前,许多SGLT2抑制剂已经进入临床评价后期。     

新型钠-葡萄糖共转运蛋白2抑制剂现状及其研发动态

钠-葡萄糖共转运蛋白2（SGLT-2）为2型糖尿病治疗的新靶点。SGLT-2抑制剂具有全新的降糖机制,其对能量平衡的负调控、降低体重、不依赖胰岛素降低血糖等特点,成为各大药企研发的热点。本文综述该类药物的降糖机制,分析现阶段SGLT-2抑制剂的最新研发动态。     

钠-葡萄糖协同转运蛋白2抑制剂类抗糖尿病新药的研发概况

目前,钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂通过抑制葡萄糖在肾脏近曲小管的重吸收,从而成为治疗糖尿病的新途径。按其结构,SGLT2抑制剂主要分为C-芳基抑制剂、O-芳基抑制剂、S-糖苷抑制剂和N-糖苷抑制剂,而C-芳基抑制剂和O-芳基抑制剂处于研究热点,其中几个新药(dapagliflozin、canagliflozin、ASP1941、BI10773和LX4211)显示出良好的控制血糖水平和减轻体质量的效果,且不良反应较小。综述两类结构中的主要药物研究概况,并分析其研发前景。     

胰高血糖素样肽-1受体激动剂与钠-葡萄糖协同转运蛋白-2抑制剂治疗2型糖尿病疗效及安全性的系统评价

目的：系统评价胰高血糖素样肽-1受体激动剂（GLP-1RA）与钠-葡萄糖协同转运蛋白-2抑制剂（SGLT-2i）治疗2型糖尿病（T2DM）的疗效及安全性,为临床治疗提供循证参考。方法：计算机检索相关的随机对照试验。采用Stata 14.0软件进行Meta分析,并运用成本-效果分析方法进行短期经济学评价。结果：共纳入6项RCT,合计2 248例患者,纳入药物包括利拉鲁肽、艾塞那肽、司美格鲁肽、卡格列净、达格列净和恩格列净。Meta分析结果显示：GLP-1RA能更有效地降低糖化血红蛋白（HbA1c）水平[SMD=-0.28,95% CI （-0.40,-0.16）,P<0.01],且HbA1c<7%的达标率更高,而SGLT-2i能更有效地控制患者的收缩压、舒张压和脉搏;GLP-1RA治疗组导致停药、腹泻、恶心、呕吐等不良反应的发生率均显著高于SGLT-2i治疗组,而SGLT-2i治疗组患者出现生殖器感染的发生率更高,差异均有统计学意义。SGLT-2i的成本-效果比更低。结论：GLP-1RA降低T2DM患者HbA1c水平的疗效更好,但SGLT-2i控制患者血压和脉搏的效果更优、耐受性更佳且具有较高的经济学优势,临床治疗中应根据患者的具体情况选择合适的药物。     

A consensus statement for the clinical use of the renal sodium-glucose co-transporter-2 inhibitor dapagliflozin in patients with type 2 diabetes mellitus

Introduction: The present review developed a clinical consensus based on a Delphi method on Dapagliflozin, a selective inhibitor of the renal sodium-glucose co-transporter-2 (SGLT2-I) in the treatment of patients with Type 2 diabetes mellitus.

Areas covered: Panel members, using a 5-point scale, were asked to rate 9 statements on pharmakodinamic, mode of action on glycaemic and extra-glycaemic effects, and safety of dapaglifozin, Members also aimed to identify the patient most susceptible to the treatment with dapagliflozin .

Expert commentary: Dapagliflozin is effective in lowering the plasma glucose concentration with a good safety profile. Dapagliflozin can be utilized in combination with all other antihyperglycaemic agents at all stages of the disease: however, a reduced GFR limits its efficacy. As for the other drugs of the class, Dapagliflozin positively modifies other risk factors for CV disease: these effects will be tested in the so far largest cardiovascular outcome trial for the SGLT2 inhibitors so far, the DECLARE trial, which will communicate whether this class of drugs will be disease-modifier in patients with type 2 diabetes also in primary prevention.     

Update review of the safety of sodium-glucose cotransporter 2 inhibitors for the treatment of patients with type 2 diabetes mellitus

ABSTRACT

Introduction: The safety profile of sodium-glucose cotransporter 2 (SGLT2) inhibitors has continued to evolve with the availability of data from clinical trial programs, post-marketing pharmacovigilance and dedicated cardiovascular outcome trials.

Areas covered: This article reviews the safety issues associated with the SGLT2 inhibitors canagliflozin, dapagliflozin, and empagliflozin, particularly the newer/emergent safety data related to US Food and Drug Administration statements regarding these three agents.

Expert opinion: The safety profile of SGLT2 inhibitors is well defined, and the adverse event profile is largely consistent with their mechanism of action. These well-recognized events include genital mycotic infections and volume-associated adverse events. Serious safety issues detected more recently with SGLT2 inhibitor therapy, such as bone fractures, pyelonephritis, urosepsis, and ketoacidosis, have been uncommon. A robust improvement in cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) was recently demonstrated with empagliflozin. Given the glucose-lowering efficacy, low risk of hypoglycemia, and other benefits associated with SGLT2 inhibitor therapy, this class of oral glucose-lowering medication is a valuable addition to treatment options for T2DM, and may play an increasingly prominent therapeutic role as emerging data are revealed.     

Sotagliflozin as a potential treatment for type 2 diabetes mellitus

Introduction: SGLT1 is the primary transporter responsible for the absorption of glucose and galactose in the intestine, while SGLT2 and SGLT1 are both involved in the renal reabsorption of glucose. SGLT2 inhibitors are a new class of oral antidiabetic drugs, acting by increasing urinary glucose excretion (UGE). They offer the advantages of a reduced risk of hypoglycaemia, a decrease in body weight and blood pressure and an efficacy at all stages of type 2 diabetes (T2DM).

Areas covered: Herein, the authors focus specifically on sotagliflozin (LX4211), the first-in-class dual SGLT1/SGLT2 inhibitor. Original publications in English were selected as the basis of this review. Clinical trials were identified using the Clinicaltrial.gov database.

Expert opinion: By a potential additional mechanism of action on intestinal glucose absorption linked to SGLT1 inhibition, sotagliflozin differentiates from SGLT2 inhibitors by reducing postprandial glucose excursion and insulin secretion, as well as by increasing GLP-1 secretion. Despite a weaker effect on UGE than selective SGLT2 inhibitors, sotagliflozin is as effective as SGLT2 inhibitors on HbA1C reduction, with a similar safety profile in short-term studies. While sotagliflozin was first assessed in T2DM, it is now in phase 3 development as an adjuvant treatment in patients with T1DM after positive results from a pilot study.