不同类型SGLT2抑制剂对心力衰竭合并2型糖尿病患者临床预后的影响观察

目的 调查钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂对心力衰竭合并2型糖尿病患者临床预后的影响。方法 选自2020年6月至2020年12月于北京京煤集团总医院心内科住院的心力衰竭(心衰)合并2型糖尿病的患者50例,随机分为三组:对照组、卡格列净组和达格列净组。对照组采用常规治疗方案,卡格列净组和达格列净组分别在常规治疗基础上加用卡格列净和达格列净。出院随访1年,比较三组患者糖化血红蛋白(HbA1C)、左室射血分数(LVEF)、脑钠肽(BNP)及心衰再住院率情况。结果治疗后3组患者间HbA1C及心衰再住院率无明显差异。治疗后卡格列净组LVEF 53.47%,达格列净组LVEF 53.13%,均高于对照组(LVEF 45.53%),三组间LVEF差异具有统计学意义(P<0.05),卡格列净组及达格列净组间无明显差异。治疗后卡格列净组BNP 238.59 pg/ml及达格列净组BNP 379.78 pg/ml,均低于对照组(BNP 724.41 pg/ml),差异具有统计学意义(P<0.05),卡格列净组与达格列净组间无差异。结论 SGLT2抑制剂卡格列净及达格列净均可改善心衰...     

SGLT2抑制剂肾脏外糖代谢调控机制的研究进展

钠-葡萄糖协同转运蛋白2抑制剂(SGLT2i)是一类新型的口服降血糖药物,其除了良好的降糖效果,还能降低血尿酸、尿蛋白排泄、血压和体重等,有效降低2型糖尿病患者的心、肾等并发症的发病风险。以往的观点认为,SGLT2i的降糖作用主要通过抑制肾脏近端小管葡萄糖的重吸收,从而降低肾糖阈,促进尿糖排泄,降低血糖。最近几年人们发...     

钠-葡萄糖协同转运蛋白2抑制剂改善心脏重构及其机制

心脏重构是心力衰竭(心衰)发生和发展的重要决定因素。钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂作为一种新型抗糖尿病药物, 具有潜在的抗心脏重构作用, 改善心衰患者预后。本文主要综述SGLT2抑制剂逆转不良心脏重构的潜在效应及其相关机制。     

SGLT⁃2抑制剂治疗1型糖尿病的心血管保护作用

T1DM与早发性心血管疾病密切相关.有些T1DM患者血糖控制未达标,需辅助疗法以助其实现达标.钠?葡萄糖协同转运蛋白2抑制剂(SGLT?2i)是独立于Ins作用机制的新型降糖药,SGLT?2i辅助治疗T1DM可改善血糖、血脂、血尿酸、尿蛋白异常,降低体重、BP等心血管事件高危因素且减少每日Ins用量.本文对SGLT?2...     

葡萄糖协同转运蛋白2抑制剂防治心力衰竭的研究进展

心力衰竭是合并动脉粥样硬化性心血管疾病(ASCVD)和ASCVD高危因素2型糖尿病(T2DM)患者最常见的并发症之一。临床试验显示葡萄糖协同转运蛋白2抑制剂(SGLT2i)可有效预防心力衰竭住院的发生。新的证据表明SGLT2i治疗确诊的合并和不合并T2DM的心力衰竭患者明显获益,更多的循证医学依据正在积累中。虽然SGLT2i耐受性良好,但应对严重不良作用进行监测。本文主要介绍SGLT2i防治心力衰竭的获益、不良作用和可能机制。     

SGLT2抑制剂对胰岛β细胞的保护作用及潜在机制

保护胰岛β细胞是糖尿病治疗的重要策略。新型降糖药物钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂通过抑制肾小管对葡萄糖的重吸收来降低血糖,该降糖作用不依赖胰岛素。多项临床研究发现,该类药物可明显改善β细胞功能。动物研究显示,SGLT2抑制剂可增加β细胞总量。SGLT2抑制剂促进β细胞再生有以下几种方式：促进β细胞增殖、抑...     

SGLT2抑制剂的心血管获益及治疗心力衰竭的研究综述

心力衰竭（心衰）是多种心血管疾病的严重终末阶段,尽管其药物治疗已取得很大进步,但其预后仍不乐观,接受标准治疗的心衰患者仍存在高死亡和再住院风险。目前已有多项大型随机对照研究证实降糖药物钠-葡萄糖共转运蛋白2（SGLT2）抑制剂有明显的心血管获益,可以明显降低心衰患者心血管死亡率,降低心衰恶化风险,且无论是否伴有糖尿病均可获益。本文就SGLT2抑制剂的心血管获益和治疗心衰的研究和机制进行综述,期待SGLT2抑制剂可以打破传统心衰治疗的金三角（血管紧张素转化酶抑制剂/血管紧张素II受体拮抗剂/血管紧张素受体脑啡肽酶抑制剂、盐皮质激素受体拮抗剂和β受体阻滞剂）,实现与金三角使用的四联治疗。     

SGLT2抑制剂治疗2型糖尿病的相关研究

钠-葡萄糖协同转运蛋白2( SGLT2)存在于近端肾小管上皮细胞,在肾脏血糖的重吸收中发挥重要作用,因此选择性抑制SGLT2活性,从而特异性抑制肾脏对葡萄糖的重吸收,增加尿糖排泄可以达到降糖目的.目前研发的SGLT2抑制剂包括T-1095、BI-10773、dapagliflozin等.SGLT2抑制剂与体重、低血糖、糖尿病肾病、泌尿系统感染及口渴、多饮、多尿症状的关系未明确,目前已有大量研究证明了其有效性及安全性,这将为糖尿病患者提供一种新的降糖途径.     

SGLT2抑制剂治疗2型糖尿病合并心力衰竭的疗效和安全性的Meta分析

目的 系统评价钠-葡萄糖共转运蛋白2抑制剂(SGLT2i)治疗2型糖尿病(T2DM)合并心力衰竭(心衰,HF)的有效性和安全性.方法 系统检索了CocHRane图书馆、Web of science、PubMed、Embase数据库,检索时限均为建库起至2020年11月20日,搜索了SGLT2i对比安慰剂治疗T2DM合并...     

舒张性心力衰竭早期防治专家建议

舒张性心力衰竭(DHF)已经成为一个公共健康问题,其发病主要涉及心血管代谢危险因素(CMRF)人群。对于DHF早期诊断,本专家组建议推荐超声心动图测量左室舒张功能指标和检测利钠肽水平;在治疗高血压、高脂血症、2型糖尿病(T2D)及肥胖等CMRF时,推荐应用SGLT2抑制剂、二甲双胍、GLP-1受体激动剂和他汀等药物进行心外膜脂肪组织(EAT)聚集的早期干预,预防DHF。     

Uric acid and the cardio-renal effects of SGLT2 inhibitors

Sodium/glucose co-transporter-2 (SGLT2) inhibitors, which lower blood glucose by increasing renal glucose elimination, have been shown to reduce the risk of adverse cardiovascular (CV) and renal events in type 2 diabetes. This has been ascribed, in part, to haemodynamic changes, body weight reduction and several possible effects on myocardial, endothelial and tubulo-glomerular functions, as well as to reduced glucotoxicity. This review evaluates evidence that an effect of SGLT2 inhibitors to lower uric acid may also contribute to reduced cardio-renal risk. Chronically elevated circulating uric acid concentrations are associated with increased risk of hypertension, CV disease and chronic kidney disease (CKD). The extent to which uric acid contributes to these conditions, either as a cause or an aggravating factor, remains unclear, but interventions that reduce urate production or increase urate excretion in hyperuricaemic patients have consistently improved cardio-renal prognoses. Uric acid concentrations are often elevated in type 2 diabetes, contributing to the “metabolic syndrome” of CV risk. Treating type 2 diabetes with an SGLT2 inhibitor increases uric acid excretion, reduces circulating uric acid and improves parameters of CV and renal function. This raises the possibility that the lowering of uric acid by SGLT2 inhibition may assist in reducing adverse CV events and slowing progression of CKD in type 2 diabetes. SGLT2 inhibition might also be useful in the treatment of gout and gouty arthritis, especially when co-existent with diabetes.     

钠-葡萄糖共转运蛋白2抑制剂在心力衰竭中的作用

研究发现,心力衰竭(heart failure,HF)是65岁以上老年人住院的首要原因之一,导致严重的临床和经济负担,而钠-葡萄糖共转运蛋白2(sodium-dependent glucose cotransporters 2,SGLT-2)抑制剂有降低HF发生的作用。SGLT-2抑制剂是一类兼有心血管获益的口服降糖药。目前,全球已有7个SGLT-2抑制剂上市,其中4个已经获得美国食品药品监督管理局批准、并在美国临床应用,包括卡格列净(canagliflozin,强生公司,2013年3月上市)、恩格列净(empagliflozin,勃林格殷格翰和礼来公司,2014年8月上市)、达格列净(dapagliflozin,阿斯利康和百时美施贵宝公司,2014年1月上市)以及埃格列净(ertugliflozin,辉瑞和默沙东公司,2017年12月上市),上述药物的临床试验均显示了SGLT-2抑制剂可减少HF发生率[1]。     

SGLT2 inhibitors and the kidney: Effects and mechanisms

Aims

Numerous clinical trials have shown that sodium glucose cotransporter 2 (SGLT2) inhibitors exert a favorable effect on the indices of renal function (albuminuria, glomerular filtration rate decline over time) and the incidence of hard renal endpoints such as renal death or time to initiation of renal replacement therapy.

Effects of sodium glucose cotransporter type 2 inhibitors on heart failure

Heart failure (HF) is emerging as one of the most common cardiovascular (CV) events in patients with type 2 diabetes (T2D), and the one associated with the worst prognosis. T2D and insulin resistance are strong predictors of incident HF, especially HF with preserved ejection fraction (HFpEF). Recent data suggest that even when all traditional risk factors for ASCVD are well controlled, patients with T2D continue to have a substantially greater risk of developing HF—indicating that traditional risk factor control is insufficient from a HF prevention standpoint, and highlighting the need for novel, more effective strategies for both prevention and treatment of heart failure in patients with T2D. Until recently, medications developed for glucose-lowering had, at best, neutral effect on heart failure outcomes in patients with T2D, while several classes of T2D medications had little data in regards to HF risk, and others actually increased the risk of HF hospitalization. Sodium glucose cotransporter type 2 inhibitors (SGLT-2i) have a novel and unique mechanism of action. By inhibiting sodium and glucose reabsorption in the proximal tubule, SGLT-2i result in a number of downstream effects, including glucosuria, weight loss, osmotic diuresis and natriuresis, which should theoretically be beneficial in HF. Three CVOTs of various SGLT-2i (EMPA-REG OUTCOME, CANVAS and DECLARE-TIMI 58) enrolled markedly different patient populations in terms of ASCVD risk, but have demonstrated robust and consistent benefits in reduction of hospitalization for HF. In a meta-analysis of the three outcomes trials, SGLT-2i significantly reduced the risk of cardiovascular death or hospitalization for HF by 23% and hospitalization for HF by 31%. Although the declines in HF hospitalization with SGLT-2is are impressive, only a small proportion of patients with established HF were enrolled in these trials, and these benefits, therefore, represent primarily a HF prevention signal. Whether this prevention of HF benefit will translate to better outcomes for those patients with established HF (with or without diabetes), and whether it will extend across the spectrum of HF phenotypes (HFrEF and HFpEF) is yet to be determined, and is being actively investigated in several large ongoing trials.     

Sodium–glucose cotransporter 2 inhibitors in heart failure with preserved ejection fraction: A protocol for meta-analysis

Background:Nearly half of patients with heart failure (HF) have preserved ejection fraction (EF) and the mortality and morbidity of patients with HF with preserved EF (HFpEF) are high. Patients with HFpEF are often elderly and their primary chronic symptom is severe exercise intolerance that results in a reduced quality of life. Thus, improvement of exercise capacity presents another important clinical outcome in HFpEF patients. Recent randomized controlled trials (RCTs) and meta-analyses of RCTs reported that sodium–glucose cotransporter 2 (SGLT-2) inhibitors improved cardiovascular outcomes in patients with HF with reduced EF. Although the effects of SGLT-2 inhibitors in HFpEF patients have been examined in multiple RCTs, the results are inconsistent due partly to limited power. The purpose of this meta-analysis is to evaluate the efficacy and safety of SGLT-2 inhibitors in HFpEF patients.Methods:This meta-analysis will include RCTs examining the effects of SGLT-2 inhibitors on HF severity and health-related quality of life in HFpEF patients. Information of studies will be collected from electronic databases. The primary outcome will be HF severity (plasma B-type natriuretic peptide levels and exercise capacity assessed as 6-minute walk distance). The secondary outcome will be health-related quality of life. The safety outcomes will be all-cause death, HF hospitalization, hypotension, acute renal failure, diabetic ketoacidosis, and urinary tract infection.Discussion:This meta-analysis will evaluate the efficacy and safety of SGLT-2 inhibitors in HFpEF patients, providing evidence to the clinical use of SGLT-2 inhibitors in these patients.Systematic review registration:INPLASY2021120033     

Sodium glucose cotransporter 2 inhibitors: New horizon of the heart failure pharmacotherapy

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have gained momentum as the latest class of antidiabetic agents for improving glycemic control. Large-scale clinical trials have reported that SGLT2 inhibitors reduced cardiovascular outcomes, especially hospitalization for heart failure in patients with type 2 diabetes mellitus who have high risks of cardiovascular disease. Accumulating evidence has indicated that beneficial effects can be observed regardless of the presence or absence of type 2 diabetes mellitus. Accordingly, the Food and Drug Administration approved these agents specifically for treating patients with heart failure and a reduced ejection fraction. It has been concluded that canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin can be recommended for preventing hospitalization associated with heart failure in patients with type 2 diabetes and established cardiovascular disease or those at high cardiovascular risk. In the present review, we explore the available evidence on SGLT2 inhibitors in terms of the cardioprotective effects, potential mechanisms, and ongoing clinical trials that may further clarify the cardiovascular effects of the agents.     

Ketosis and diabetic ketoacidosis in response to SGLT2 inhibitors: Basic mechanisms and therapeutic perspectives

Inhibitors of the sodium‐glucose cotransporter SGLT2 are a new class of antihyperglycemic drugs that have been approved for the treatment of type 2 diabetes mellitus (T2DM). These drugs inhibit glucose reabsorption in the proximal tubules of the kidney thereby enhancing glucosuria and lowering blood glucose levels. Additional consequences and benefits include a reduction in body weight, uric acid levels, and blood pressure. Moreover, SGLT2 inhibition can have protective effects on the kidney and cardiovascular system in patients with T2DM and high cardiovascular risk. However, a potential side effect that has been reported with SGLT2 inhibitors in patients with T2DM and particularly during off‐label use in patients with type 1 diabetes is diabetic ketoacidosis. The US Food and Drug Administration recently warned that SGLT2 inhibitors may result in euglycemic ketoacidosis. Here, we review the basic metabolism of ketone bodies, the triggers of diabetic ketoacidosis, and potential mechanisms by which SGLT2 inhibitors may facilitate the development of ketosis or ketoacidosis. This provides the rationale for measures to lower the risk. We discuss the role of the kidney and potential links to renal gluconeogenesis and uric acid handling. Moreover, we outline potential beneficial effects of modestly elevated ketone body levels on organ function that may have therapeutic relevance for the observed beneficial effects of SGLT2 inhibitors on the kidney and cardiovascular system.     

氨甲酰化促红细胞生成素逆转慢性心力衰竭大鼠心肌重塑的作用

目的:观察血清基质金属蛋白酶-2(Matrix metalloproteinase-2, MMP-2)及其组织抑制因子(Tissue inhibitor of metalloproteinase-1, TIMP-1)水平与心肌胶原容积指数(CVF)的变化,探讨氨甲酰化促红细胞生成素(CEPO)对慢性心力衰竭(CHF)心肌重塑的作用及其机制.方法:从80只Wistar雄性大鼠中随机选取10只作为对照组,其余腹腔注射异丙肾上腺素建立CHF模型.5周后将造模成功的大鼠再随机分为2组:CHF组(n=18);CEPO组(n=18),腹腔注射CEPO 50 μg/kg,2次/周,连续4周.CHF组和对照组同期腹腔注射等量0.9%氯化钠溶液.4周后检测3组大鼠血流动力学指标、左心室重量指数(LVMI)和血清MMP-2及TIMP-1水平与CVF的变化.结果:与对照组相比,CHF组左室收缩压(LVSP)、左室内压上升/下降最大速率(±dp/dtmax)绝对值均显著降低(P<0.01),左室舒张压(LVDP)、左室舒张末压(LVEDP)升高(P<0.01),血清MMP-2升高(P<0.01)而TIMP-1降低(P<0.01),LVMI及CVF升高(P<0.01);与CHF组相比,CEPO组大鼠血流动力学各指标变化均有显著差异(P<0.01),血清MMP-2水平降低(P<0.01)、TIMP-1水平升高(P<0.01),LVMI及CVF降低(P<0.01).结论:CEPO有明确的抗心力衰竭作用,通过调节MMP-2和TIMP-1的表达,降解细胞外基质胶原含量,逆转心肌重塑,从而改善心脏功能.