钠-葡萄糖共转运蛋白2抑制剂对2型糖尿病患者肾脏保护作用的研究进展

钠-葡萄糖共转运蛋白2抑制剂(SGLT2i)是一类非胰岛素依赖的新型口服降糖药物,其通过抑制肾脏近曲小管钠.葡萄糖共转运蛋白2(SGLT2)的活性来减少原尿中葡萄糖的重吸收,促进尿糖排泄并降低血糖.SGLT2i还可降低血压、动脉僵硬度、血尿酸,调节肾脏血流动力学,抑制肾素-血管紧张素系统(RAS)和交感神经系统(SNS),减轻炎症和氧化应激,以及改善肾脏缺氧,发挥肾脏保护作用.本文就SGLT2在肾脏糖代谢调节中的作用及SGLT2i对肾脏保护作用的研究进展和相应机制作综述.     

钠-葡萄糖共转运蛋白2抑制剂治疗心力衰竭的研究进展

心力衰竭(heart failure,HF)是心血管疾病的晚期表现和终末期阶段,具有较高的患病率、病死率,患者因反复住院、活动耐力下降而严重影响生活质量。钠-葡萄糖共转运蛋白2(sodium-glucose cotransporter 2,SGLT2)抑制剂是一种通过抑制肾小管上皮细胞SGLT2的降血糖药物,其通过降低血容量、减轻心脏负荷,改善心脏能量代谢、抑制心室重塑,改善心脏微血管、保护血管内皮功能,抑制心脏钠转运蛋白,增加红细胞压积和血红蛋白,维持线粒体自噬平衡等机制改善HF患者的症状,降低心血管死亡风险和再住院率。SGLT2抑制剂在治疗HF时有良好的心血管获益及安全性,但因SGLT2抑制剂的长期使用时安全性不明,所以临床医师在使用过程中应需密切观察,及时发现一些隐匿的不良反应,避免不良事件发生。     

钠-葡萄糖协同转运蛋白2抑制剂在2型糖尿病治疗中的研究进展

钠-葡萄糖协同转运蛋白2抑制剂(SGLT-2 i)类药物是近年来临床用于治疗2型糖尿病的一种新型口服降糖药物,此类药物作用机制为通过抑制肾小管钠-葡萄糖协同转运蛋白2,降低肾糖阈,减少近端肾小管葡萄糖重吸收,排出多余葡萄糖,从而达到降低患者血糖的目的.此外,该类药物还具有减轻尿蛋白、保护心脏、降压、减重、改善胰岛素抵抗...     

钠-葡萄糖协同转运蛋白2抑制剂对糖尿病肾病保护作用的研究进展

糖尿病肾病(diabetic nephropathy, DN)是糖尿病最严重的微血管并发症之一,现已成为终末期肾脏病的重要病因,因此防治DN的发生和发展是当今需要迫切解决的重要课题。钠-葡萄糖协同转运蛋白2(sodium-dependent glucose transporters 2, SGLT2)抑制剂(SGLT2 inhibition, SGLT2i)是一种新型降糖药物,可通过抑制肾脏近端小管的重吸收和促进尿中葡萄糖的排泄来降低血糖,被广泛用于2型糖尿病(diabetes mellitus type 2,T2DM)的治疗。SGLT2i不仅可以降低血糖,还可以保护肾脏,延缓肾功能衰竭的进展,改善患者生活质量。本文就SGLT2i对DN的肾脏保护作用机制作一综述,为DN的预防、治疗及新型降糖药物的应用提供理论基础。     

钠-葡萄糖协同转运蛋白2抑制剂肾脏保护作用的研究进展

钠-葡萄糖协同转运蛋白2抑制剂(sodium-dependent glucose transporters 2 inhibition,SGLT2i)是一种新型降糖药,以近端肾小管的钠-葡萄糖协同转运蛋白2(sodium-dependent glucose transporters 2,SGLT2)为作用靶点,上市初期以降糖为主要目的。既往有关SGLT2i对糖尿病患者心肾保护作用的研究发现,该药除具有不依赖胰岛素降糖的独特作用外,且对无论是否患有2型糖尿病的慢性肾脏病(chronic kidney disease,CKD)患者均具有肾脏保护作用。本文通过汇总近年来SGLT2i肾脏保护的相关临床研究并对SGLT2i肾脏保护的潜在机制进行综述,旨在为未来SGLT2i可能在非糖尿病肾病患者中的应用提供一定的理论依据。     

钠-葡萄糖协同转运蛋白2抑制剂对IgA肾病肾脏保护作用的研究进展

IgA肾病(IgA nephropathy, IgAN)是我国最常见的原发性肾小球疾病,也是引起终末期肾病(end-stage renal disease, ESRD)的重要原因,可发生于任何年龄段,但以青年男性最为多见。钠-葡萄糖协同转运蛋白2(sodium-glucose transporter 2,SGLT2)抑制剂是一种新型降糖药物,已在2型糖尿病(diabetes mellitus type 2,T2DM)患者中广泛应用。随着认识的不断深入,研究发现SGLT2抑制剂不仅可降低IgAN患者尿蛋白与血压、调节肾脏血流动力学、控制尿酸及体重,甚至对肾脏炎症及纤维化也有着积极的影响,可通过多种途径对肾脏起保护作用,有望治疗和延缓IgAN。本文通过对SGLT2抑制剂对IgAN肾脏保护的研究进展进行综述,旨在提供理论依据。     

钠-葡萄糖协同转运蛋白2抑制剂在心房颤动发生中的应用研究进展

心房颤动的发病率不断增加,同时也是导致心脑血管不良事件的重要因素,需要新的和有效的治疗方案。糖尿病患者被认为面临着更高的心房颤动风险,钠-葡萄糖协同转运蛋白2抑制剂(SGLT2i)作为新型降糖药物应用于临床,除控制血糖外,因其可以发挥明显的心血管益处而备受关注。但人们对其抗心律失常的特性知之甚少,SGLT2i最近被用于房颤的治疗,大量的证据表明这类药物减少了2型糖尿病患者心房颤动事件的发生率。本文就SGLT2i作为一种不断发展的心房颤动治疗手段的潜在机制以及基础和临床数据进行综述。     

钠-葡萄糖共转运蛋白2抑制剂治疗射血分数轻度降低的心力衰竭患者疗效及安全性分析

目的 探讨射血分数轻度降低的心力衰竭（heart failure with mildly reduced ejection fraction,HFmr EF）患者钠-葡萄糖共转运蛋白2抑制剂治疗疗效及安全性。方法 选取安徽中医药大学附属铜陵中医医院2022年1—8月85例HFmr EF患者,按照随机数字表法分为观察组43例与对照组42例,对照组接受标准药物治疗方案,观察组在对照组基础上加用达格列净口服,起始剂量5mg/d,逐步增至10mg/d并维持,持续治疗3个月,比较两组临床疗效、心功能、炎性指标、肾功能指标水平及临床不良事件发生情况。结果 观察组临床治疗有效率为90.70%,高于对照组的73.81%(P<0.05);治疗后,观察组左心室舒张、收缩末期内径、左心房内径、室间隔厚度小于对照组,左心室射血分数高于对照组（P<0.05）;观察组治疗后血清炎性指标白细胞介素-6、白细胞介素-1β、肿瘤坏死因子-α水平低于对照组（P<0.05）;观察组治疗后血肌酐、血尿素氮水平低于对照组,肾小球滤过率水平高于对照组（P<0.05）;两组心血管不良事件发生率比较,差异无显...     

胰高糖素样肽-1激动剂联合钠-葡萄糖协同转运蛋白2抑制剂对2型糖尿病的影响

近年来,全球糖尿病患病率逐年增加,其中2型糖尿病(type 2 diabetes mellitus,T2DM)占糖尿病总患病人数的90%~95%。胰高糖素样肽-1(glucagon-like peptide 1,GLP-1)激动剂联合钠-葡萄糖协同转运蛋白2抑制剂(sodium-glucose co-transporter 2 inhibitor,SGLT2)是治疗T2DM的新型降糖药物。本文讨论在给予规范的生活方式(饮食和运动)干预下,GLP-1激动剂联合SGLT2抑制剂对T2DM的安全性和有效性。     

二肽基肽酶Ⅳ抑制剂在2型糖尿病合并肾功能不全老年患者中的使用情况

目的:分析二肽基肽酶Ⅳ(DPP-4)抑制剂在2型糖尿病合并肾功能不全老年患者中的使用情况。方法:选择2014年1月至2018年11月于复旦大学附属中山医院就诊的2型糖尿病合并肾功能不全的65岁以上患者700例,均使用DPP-4抑制剂(维格列汀、沙格列汀、阿格列汀、西格列汀或利格列汀)。分析DPP-4抑制剂在不同年龄段、不同程度肾功能不全、不同糖化血红蛋白(HbA_(1c))水平患者中的应用情况。结果:700例老年患者中,中、重度肾功能不全者共278例(39.71%)。5种DPP-4抑制剂的年龄分布差异无统计学意义。使用利格列汀的315例患者中,有123例(39.05%)合并中度肾功能不全,53例(16.83%)合并重度肾功能不全;利格列汀在中、重度肾功能不全患者中使用的占比最高(176例,63.31%),多于其他4种药品(P0.01)。血糖控制欠佳合并中、重度肾功能不全的患者主要应用利格列汀(100例,65.36%)和西格列汀(39例,25.49%)。结论:在DPP-4抑制剂中,2型糖尿病合并中、重度肾功能不全的65岁以上患者主要应用利格列汀,其中血糖控制不佳者多应用利格列汀和西格列汀,符合目前指南推荐。     

SGLT2抑制剂对2型糖尿病患者心血管结局影响的网状meta分析

目的 2型糖尿病是一种慢性疾病,而心血管事件是2型糖尿病常见的并发症,已有大型研究表明钠-葡萄糖共转运体抑制剂(SGLT2i)对改善2型糖尿病患者心血管结局具有一定作用。本文通过系统评价,间接比较了5种不同的SGLT2i对2型糖尿病并发不良心血管事件的疗效作用。方法 检索PubMed、Web of science、Cochrane Library、中国知网、万方、维普数据库,收集相关文献,检索时限为建库至2022年7月,由两位研究员独立筛选文献,并提取相应数据,以心力衰竭住院和心血管死亡复合结局为主要结局指标,以心力衰竭住院、心血管死亡和全因死亡为次要结局指标,使用Stata 16.0以及network程序包进行网状meta分析。结果 共检索到340篇文献,最终纳入11篇文献,包括62 904例患者,涉及5种干预手段,分别为:恩格列净、索格列净、达格列净、埃格列净和卡格列净。5种不同的SGLT2i在改变2型糖尿病患者的心力衰竭住院和心血管死亡复合结局、心血管死亡、心力衰竭住院和全因死亡方面差异无统计学意义(P>0.05)。与安慰剂相比,5种不同的SGLT2i均可显著改善2型糖尿病患者心力衰竭住院结局;恩格列净和索格列净在改善心力衰竭住院和心血管死亡复合结局方面差异有统计学意义;而在改善心血管死亡或全因死亡结局方面,安慰剂和5种不同的SGLT2i之间的差异均无统计学意义。结论 在改善2型糖尿病患者心力衰竭住院和心血管死亡复合结局和心力衰竭住院结局方面,恩格列净和索格列净有较显著的获益趋势,而针对心血管死亡或全因死亡结局,5种不同的SGLT2i与安慰剂间的差异无统计学意义,具体机制和原因仍需大型研究进行探索和验证。     

The use of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes and hypertension: a focus on African-American populations

Diabetes, hypertension, and severe kidney disease are all disproportionately prevalent in African-Americans. Clinical trials data from type 2 diabetes (T2D) patients have demonstrated that sodium-glucose cotransporter 2 (SGLT2) inhibitors have a positive effect on cardiovascular risk factors – such as improved blood glucose control, reduced body weight, and reduced blood pressure – and also support a possible renal-protective role for SGLT2 inhibitors. The EMPA-REG OUTCOME^® trial revealed that empagliflozin was associated with reduced adverse cardiovascular and renal outcomes. Thus, SGLT2 inhibitors could potentially provide clinicians with a treatment option that addresses multiple pathophysiologic aspects of the cardiometabolic disease processes that may affect end-organ function in African-American patients with T2D and hypertension. This review examines some of the clinical issues associated with this patient group and the role that SGLT2 inhibitors may provide in their treatment.     

Clinical use of dipeptidyl peptidase-4 and sodium-glucose cotransporter 2 inhibitors in combination therapy for type 2 diabetes mellitus

Objective. To review the efficacy, safety, and tolerability of combination treatment regimens including a dipeptidyl peptidase-4 (DPP-4) inhibitor and/or sodium-glucose cotransporter 2 (SGLT2) inhibitor for type 2 diabetes mellitus (T2DM). Methods. Clinical trials of combination therapies including a DPP-4 and/or SGLT2 inhibitor were identified through a PubMed database search. To be included, studies had to have a primary end point of change from baseline to ≥24 weeks in glycated hemoglobin, include ≥1 other oral antidiabetic drug (OAD), and have randomized more than 200 patients. Results were limited to medications approved by the US Food and Drug Administration at the time of the search (March 2015). Results. A total of 1534 articles for the DPP-4 inhibitor class and 434 articles for the SGLT2 inhibitor class were retrieved from PubMed. Of these, 33 articles from the DPP-4 inhibitor class and 24 articles from the SGLT2 inhibitor class were included for review. In each study, the addition of a DPP-4 or SGLT2 inhibitor as a second or third agent resulted in improved glycemic control versus comparator arms. Reductions in weight or lack of weight gain were consistently observed, as were low rates of hypoglycemic events, particularly when the combination regimen also included metformin. Overall, the pattern of adverse events observed in combination treatment groups was consistent with the known effects of the individual agents. Conclusion. Combination treatment with a DPP-4 and/or SGLT2 inhibitor is an efficacious option for patients with T2DM starting pharmacological therapy, or for patients who have received treatment but require additional glycemic control. Study findings indicate that the underlying mechanisms of action of DPP-4 inhibitors and SGLT2 inhibitors complement a variety of OADs.     

Cardiovascular benefits and safety of non-insulin medications used in the treatment of type 2 diabetes mellitus

Diabetes mellitus is a growing in exponential proportions. If the current growth trend continues, it may result in every third adult in the United States having diabetes mellitus by 2050, and every 10^th adult worldwide. Type 2 diabetes mellitus (T2DM) confers a 2- to 3-fold increased risk of cardiovascular (CV) events compared with non-diabetic patients, and CV mortality is responsible for around 80% mortality in this population. Patients with T2DM can have other features of insulin resistance-metabolic syndrome like hypertension, lipid abnormalities, and obesity which are all associated with increased CV disease and stroke risk even in the absence of T2DM. The management of a T2DM calls for employing a holistic risk factor control approach. Metformin is the first line therapy for T2DM and has been shown to have cardiovascular beneficial effects. Intense debate regarding the risk of myocardial infarction with rosiglitazone led to regulatory agencies necessitating cardiovascular outcome trials with upcoming anti-diabetic medications. Glucagon like peptide-1 agonists and sodium glucose co-transporter-2 inhibitors have shown promising CV safety and additional CV benefit in recent clinical trials. These drugs have favorable effects on traditional CV risk factors. The findings from these studies further support that fact that CV risk factor control plays an important role in reducing morbidity and mortality in T2DM patients. This review article will discuss briefly the cardiovascular safety and benefits of the oral medications which are currently being used for T2DM and will then discuss in detail about the newer medications being investigated for the treatment of T2DM.     

SGLT2 inhibitors in patients with type 2 diabetes and renal disease: overview of current evidence

Chronic kidney disease (CKD) is a frequent complication of type 2 diabetes mellitus (T2DM) and is associated with poor clinical outcomes, including an increased risk of all-cause and cardiovascular mortality, as well as adverse economic and social effects. Slowing the development and progression of CKD remains an unmet clinical need in patients with T2DM. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are widely used for the management of T2DM and have effects beyond glucose lowering that include cardiovascular benefits and potential renoprotective effects. Although the glucose-lowering efficacy of these agents is dependent on renal function, the cardiovascular and renal benefits of SGLT2 inhibition appear to be maintained to estimated glomerular filtration levels as low as 30 mL/min/1.73 m². Clinical evidence has indicated that these agents can reduce the risk of development or worsening of albuminuria, a marker of renal damage, through a range of mechanisms. These include blood pressure lowering, reduction of intraglomerular pressure and hyperfiltration, modification of inflammatory processes, reduction of ischemia-related renal injury, and increases in glucagon levels. The blood pressure-lowering effect of SGLT2 inhibitors is maintained in people with CKD and could further contribute to reduced renal burden, as well as potentially offering synergistic effects with antihypertensive therapies in these patients. Several cardiovascular outcomes trials (CVOTs) have included renal endpoints, adding to the growing evidence of the potential renoprotective effects of these agents in patients with T2DM. Several ongoing dedicated renal outcomes trials will provide further guidance on the potential clinical role of SGLT2 inhibitors in slowing the development and progression of renal impairment in individuals with T2DM.     

Sodium-glucose cotransporter 2 inhibitors and cardiovascular outcomes

Type 2 diabetes mellitus (T2DM) is associated with an elevated risk of cardiovascular (CV) morbidity and mortality. Furthermore, many patients with T2DM have comorbidities that are risk factors for CV disease. While intensive glucose control reduces the risk of diabetic microvascular complications, its relationship to CV outcomes remains unclear. Consequently, the management of CV risk factors in patients with T2DM is complex, and factors other than blood glucose must be considered. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a class of oral glucose-lowering agents, are associated with reductions in blood pressure and body weight, in addition to decreasing hyperglycemia, and therefore have the potential to reduce CV risk in patients with T2DM. The clinical trial results of SGLT2 inhibitors regarding CV safety and outcomes are discussed, including data from the recently published EMPA-REG OUTCOME study. This trial was the first dedicated CV outcomes study to demonstrate that a glucose-lowering agent lowered CV mortality and all-cause mortality, and reduced hospitalization for heart failure in patients with T2DM at high risk of CV events.     

特泽帕肽治疗2型糖尿病患者疗效及安全性的meta分析

目的系统评价特泽帕肽治疗2型糖尿病(T2DM)患者的疗效及安全性。方法通过检索CNKI、万方、VIP、Pubmed、Embase及Cochrane library数据库获得符合纳入标准的随机对照研究(RCTs)。结果共纳入7篇RCTs,共7163名T2DM患者。Meta分析结果显示,5 mg、10 mg、15 mg 3种剂量的特泽帕肽降低糖化血红蛋白(HbA_(1)c)、减轻体重的疗效均明显优于所有对照组[胰高血糖素样肽1受体激动剂(GLP-1RA)、胰岛素、安慰剂],疗效呈剂量依赖性,随剂量增高,显示出更大的疗效,3种剂量下HbA_(1)c降低的幅度分别为[MD=-0.98,95%CI(-1.34,-0.62)]、[MD=-1.21,95%CI(-1.53,-0.89)]、[MD=-1.37,95%CI(-1.70,-1.03)];体重降低幅度分别为[MD=-6.05,95%CI(-8.58,-3.52)]、[MD=-8.56,95%CI(-11.14,-5.98)]、[MD=-10.60,95%CI(-13.24,-7.97)](均P<0.01)。在降低空腹血糖(FPG)方面,10 mg、15 mg两种剂量降低FPG的疗效均优于所有对照组(GLP-1RA、胰岛素、安慰剂),疗效呈剂量依赖性,FPG降低的幅度分别为[MD=-1.47,95%CI(-2.23,-0.70)]、[MD=-1.55,95%CI(-2.27,-0.83)](均P<0.01),5 mg剂量组降低FPG的疗效优于安慰剂,但5 mg特泽帕肽与对照组(GLP-1RA或胰岛素)相比,降低FPG的疗效无明显差异。在HbA_(1)c<7%、HbA_(1)c≤6.5%、HbA_(1)c<5.7%的达标率及体重减少≥5%、体重减轻≥10%、体重减少≥15%的比例方面也存在剂量依赖性,随剂量增加,HbA_(1)c达标率及体重减少的比例增加。安全性方面,特泽帕肽的低血糖发生率与GLP-1RA、安慰剂相似,但低于德谷/甘精胰岛素。在胃肠道不良反应方面,与安慰剂相比,3种剂量特泽帕肽治疗后出现胃肠道不良反应的比例均高于安慰剂。在特泽帕肽与对照组(GLP-1RA或胰岛素)的比较中,特泽帕肽10 mg、15 mg剂量治疗后出现胃肠道不良反应的比例均高于对照组(GLP-1RA或胰岛素),但是特泽帕肽5 mg与对照组相比,出现胃肠道不良反应的比例无明显差异。结论与安慰剂、GLP-1RA和胰岛素相比,特泽帕肽在降低HbA_(1)c、FPG、减轻体重方面具有明显的剂量依赖性优势,没有增加低血糖风险,但10 mg及15 mg特泽帕肽与胃肠道不良事件的发生率增加有关。     

动态血糖监测研究2型糖尿病强化治疗中的血糖漂移

目的通过动态血糖监测系统（CGMS）研究2型糖尿病（T2DM）强化治疗过程中低血糖发生的特征。方法（1）将研究对象分为胰岛索治疗组、磺脲类治疗组和诺和龙治疗组；（2）用CGMS对66例T2DM患者于血糖稳定后进行72h血糖监测，其间监测指端血糖谱并输入CGMS以校正，根据血糖测定图谱观察各组低血糖发生的特征。并对每一患者抽血检测升糖相关激素，比较低血糖发生时与非低血糖时升糖相关激素的异同。结果（1）各组低血糖多于11：00—12：00，21：00一次日5：00发生，最多见于2：00。（2）餐后3h血糖较餐后2h可以更好地预测低血糖的发生。（3）发生低血糖时，升糖相关激素变化不明显。（4）磺脲类治疗组较胰岛索治疗组、诺和龙治疗组低血糖发生率明显升高。结论CGMS能及时准确地发现低血糖，了解低血糖的影响因素及低血糖后的反应，以指导临床治疗，制定针对性的治疗方案。