SGLT-2抑制剂与2型糖尿病心血管风险的研究进展

回顾评估钠-葡萄糖协同转运蛋白2(SGLT-2)抑制剂对糖尿病并发心血管疾病的作用,从临床试验数据和基础研究结果中获得证据,以阐明SGLT-2抑制剂对心血管系统疾病的危险因素以及预后的影响。对已发表在PubMed上的出版物、临床试验资料库注册的试验以及相关指南共识等进行全面系统的检索。SGLT-2抑制剂诱导多效应作用,可降低糖尿病患者并发心血管相关疾病的风险。SGLT-2抑制剂应被视为合并心血管疾病高风险的糖尿病患者进行血糖控制的临床一线药物。     

2型糖尿病的克星——SGLT-2抑制剂

SGLT-2抑制剂为非胰岛素依赖型药物,可选择性抑制SGLT-2,抑制肾小管对葡萄糖重吸收,增加尿糖排泄以降低血糖,且不易引起低血糖.SGLT-2抑制剂包括糖苷类及非糖苷类.本文重点介绍已上市药物卡格列净、达格列净、伊格列净、鲁格列净的药动学、药效学、不良反应与药物联用.     

SGLT-2抑制剂对心血管保护作用的研究概况

钠-葡萄糖协同转运蛋白-2(SGLT-2)抑制剂是一类新型的治疗2型糖尿病的药物,降糖效果好,不良反应发生率低,近年来有研究发现,除降糖作用以外,SGLT-2抑制剂还具有心血管保护作用。本文将从对心血管危险因素的影响、对肾脏的影响、降低尿酸、减少炎症、改善心脏能量代谢以及预防心脏重构等方面概述SGLT-2抑制剂的心血管保护作用。     

2型糖尿病治疗药物——SGLT-2抑制剂研究进展

钠-葡萄糖协同转运蛋白-2抑制剂通过减少人体肾脏对葡萄糖的重吸收,增加尿糖的排泄,达到降低血液中葡萄糖水平的目的,从而成为治疗2型糖尿病的新途径。近年来,SGLT-2抑制剂类药物也不断的问世,给2型糖尿病患者的治疗带来了新的希望。     

SGLT-2抑制剂和GLP-1受体激动剂的心血管安全性研究进展

2型糖尿病是动脉粥样硬化性心血管疾病发病的高危因素。研究发现,钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂、胰高血糖素样多肽-1(GLP-1)受体激动剂对2型糖尿病合并心血管疾病的患者具有心血管保护作用。故从心血管安全性试验及其Meta分析、网状Meta分析方面,对SGLT-2抑制剂、GLP-1受体激动剂的心血管安全性研究进展进行归纳和总结。     

SGLT2抑制剂在2型糖尿病人群中心血管获益证据及机制的最新研究进展

心血管不良事件是2型糖尿病患者的主要并发症,也是其死亡的首要原因.钠葡萄糖协同转运蛋白2抑制剂作为一种新型降糖药物,在2型糖尿病患者中的心血管获益已被众多大型临床试验证实.该文回顾了近期相关文献,就钠葡萄糖协同转运蛋白2抑制剂的心血管获益临床证据及其机制进行了综述.     

SGLT-2抑制剂使2型糖尿病患者获益机制研究进展

钠-葡萄糖共转运蛋白-2抑制剂（SGLT-2is）是治疗2型糖尿病（T2DM）的一种降糖药物,其通过作用于肾脏发挥降糖作用。目前相关指南已经提出将SGLT-2is用于伴有心力衰竭或慢性肾脏病的T2DM患者。多项研究表明SGLT-2is可以影响代谢状态,减少心血管事件发生和改善糖尿病肾病预后。关于SGLT-2is如何让T2DM患者获益,目前机制仍在探索中。本文对SGLT-2is作用机制进一步研究,有望为后续治疗提供依据。     

SGLT-2抑制剂及GLP-1受体激动剂治疗2型糖尿病的心血管获益：一项系统回顾和网状Meta分析

目的 通过贝叶斯网状Meta分析系统评价上市的11种钠-葡萄糖共转运蛋白-2(SGLT-2)抑制剂和胰高血糖素样多肽-1(GLP-1)受体激动剂治疗2型糖尿病患者的心血管获益。方法 检索Medline、Embase和Cochrane数据库,检索日期为建库至2020年7月18日。研究终点为心血管不良事件,效应指标为风险比（hazard ratios, HR）及其95%可信区间（95%CI）。结果 与安慰剂相比,恩格列净、卡格列净、达格列净、阿必鲁肽、度拉糖肽、艾塞那肽、利拉鲁肽和索马鲁肽可降低2型糖尿病患者主要心血管不良事件的发生风险,HR及95%CI为0.75(0.60-0.95)～0.90(0.82-0.99);恩格列净、卡格列净、达格列净和艾托格列净可降低心力衰竭的发生风险,HR及95%CI为0.64(0.49-0.82)～0.74(0.65-0.85);恩格列净、卡格列净、达格列净、艾塞那肽、利拉鲁肽和口服索马鲁肽可降低全因死亡的发生风险,HR及95%CI为0.52(0.33-0.84)～0.89(0.80-0.99);恩格列净、卡格列净、利拉鲁肽和口服索马鲁肽可降低心血管死亡事...     

Cardiovascular safety of therapies for type 2 diabetes

Introduction: Dipeptidyl peptidase-4 (DPP4) inhibitors, glucagon-like peptide-1 (GLP-1) analogs and sodium-glucose cotransporter 2 (SGLT2) inhibitors are relatively new therapies for the treatment of type 2 diabetes mellitus. Given the high prevalence of cardiovascular complications in patients with type 2 diabetes and recent concerns questioning CV safety of newer antidiabetic medications, cardiovascular safety of these medications requires evaluation.

Areas covered: Cardiovascular effects of these drug classes from preclinical and clinical data as well as non-cardiovascular safety issues are delineated from literature searches covering the last decade and up to June 2016. Major clinical trials assessing the cardiovascular safety of GLP-1 agonists (ELIXA and LEADER), DPP-4 inhibitors (SAVOR-TIMI 53, EXAMINE, and TECOS) and SGLT2 inhibitors (EMPA-REG OUTCOME) are reviewed and interpreted.

Expert opinion: Based on review of the present evidence, these 3 classes of antihyperglycemic therapies have acceptably safe CV safety profiles for patients with type 2 diabetes. The latest evidence from LEADER and EMPA-REG OUTCOME trials indicate that liraglutide and empagliflozin have cardiovascular benefits that may prove to be of clinical importance in the management of type 2 DM.     

An evaluation of the efficacy and safety of Tofogliflozin for the treatment of type II diabetes

Introduction: Accumulating data from recent studies has altered the gold standard of care for diabetes treatment. In patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or those at high risk for CVD, subsequently to lifestyle changes and metformin therapy, the administration of an SGLT-2 inhibitor with established benefits for cardiovascular outcome (CVOT) should be considered.

Areas covered: Tofogliflozin is the most selective SGLT-2 inhibitor and has been approved for the treatment of T2D in Japan. This review summarizes the available data on Tofogliflozin as compared to other SGLT-2 inhibitors, and primarily the three SGLT-2 inhibitors with published CVOT: Empagliflozin, Canagliflozin and Dapagliflozin.

Expert opinion: Tofogliflozin’s higher selectivity profile increases the positive effects on cardiovascular (CV) outcomes and death and reduces side effects. However, the clinical data on Tofogliflozin from both clinical and real-world studies remain sparse and much less abundant than the other main 3 SGLT-2 inhibitors, thus calling for caution and underscoring the need for further research.     

钠-葡萄糖共转运蛋白2抑制剂致急性胰腺炎文献分析

目的：探讨钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂致急性胰腺炎发生的规律和特点,为临床合理用药提供参考。方法：检索2013—2020年中国学术期刊全文数据库（CNKI）,维普中文科技期刊数据库（VIP）、Pubmed、Wiley、EBSCO等数据库,收集SGLT-2抑制剂致急性胰腺炎的个案报道,进行统计分析。结果：检索到个案报道9篇,共有患者9例,其中男性5例（55.6%）,女性4例（44.4%）,年龄26～71岁,原患疾病均为2型糖尿病,合并高脂血症的1例,合并高血压的3例。服用的SGLT-2抑制剂中达格列净2例,卡格列净4例,恩格列净3例,合并使用二甲双胍8例,西格列汀2例,利拉鲁肽1例。急性胰腺炎发生在用药后1～104天,主要发生在用药30天内（77.8%）。临床症状表现为腹痛、食欲减弱、恶心、呕吐,实验室检查可见血淀粉酶和脂肪酶升高。经停药、补液、止吐、镇痛等对症治疗后可恢复。结论：临床用药过程中应加强SGLT-2抑制剂致急性胰腺炎的监测,尤其是对于肾功能不全者合并使用二甲双胍,或合并使用二肽基肽酶4抑制剂或胰高血糖素样肽1类似物的患者,警惕急性胰腺炎的发生。     

Tofogliflozin: the road goes ever on

Several drugs are available for the treatment of type 2 diabetes mellitus (T2DM), but few patients achieve and maintain glycaemic control without weight gain and hypoglycaemias. Sodium glucose co-transporter 2 (SGLT-2) inhibitors are an emerging class of drugs with an original mechanism of action involving inhibition of renal glucose reabsorption. Two agents of this class, dapagliflozin and canagliflozin, have already been approved, although we need more data on cardiovascular outcomes along with bladder and breast cancer. Tofogliflozin is a further SGLT-2 inhibitor, which exhibits the highest selectivity for SGLT-2, the most potent antidiabetic action and a reduced risk of hypoglycaemia. Recently, a 52-week, multicentre, open-label, randomised controlled trial in Japanese T2DM patients has shown that tofogliflozin exhibits adequate safety and efficacy as monotherapy or as add-on treatment in patients suboptimally controlled with oral agents. Despite the very promising characteristics of this new drug, important questions remain to be answered, mainly additional data on safety outcomes and potential beneficial effects of tofogliflozin, for instance in prediabetes and diabetic nephropathy. Moreover, it would be welcome to examine the utility of its therapeutic use in combination with insulin and metformin.