新型钠–葡萄糖协同转运蛋白2抑制剂empagliflozin

钠–葡萄糖协同转运蛋白2（SGLT2）抑制剂是近年来降糖药研究的新热点,通过抑制肾小管上皮细胞内的主要血糖转运蛋白SGLT2降低肾内滤过葡萄糖的重吸收,导致糖尿,从而降低血清内葡萄糖。新型SGLT2抑制剂empagliflozin具有良好的降糖效果,单次给药就能显著增加尿中排糖,多次给药后剂量相关性地降低FPG、HbA1c和体质量,作为补充药物治疗还能显著降低血压,目前正在进行Ⅲ期临床试验。     

钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂的研究进展

钠-葡萄糖协同转运蛋白2(SGLT2)是最近新发现的糖尿病治疗新靶点,其作用机制是特异性地抑制肾脏对葡萄糖的再吸收,且不依赖于β细胞的功能异常或胰岛素抵抗的程度。其效果也不会随着β细胞功能的衰竭或严重胰岛素抵抗而下降,不会产生传统药物带来的不良反应,是糖尿病治疗的新途径。本文介绍SGLT2在调节体内糖平衡中的作用,总结SGLT2抑制剂在2型糖尿病治疗方面的最新进展,并对已报道的抑制剂化学结构进行总结。     

钠-葡萄糖转运蛋白2抑制剂与2型糖尿病患者恶性肿瘤发生风险的Meta分析

目的： 系统评价钠-葡萄糖转运蛋白2（sodium-glucose transporter 2 inhibitors,SGLT2）抑制剂的使用与2型糖尿病患者肿瘤发病的关系,为明确二者之间关系提供循证医学依据。方法： 以"钠-葡萄糖转运蛋白2（SGLT2）抑制剂、达格列净（dapagliflozin）、坎格列净（canagliflozin）、恩格列净（empagliflozin）、2型糖尿病、肿瘤"等为关键词,通过PubMed、Embase、Web of Science、Cochrane Library及万方、中国知网（CNKI）、维普中文期刊（VIP）等数据库检索2021年2月以前发表的中英文文献,确定符合条件的随机对照试验（randomized controlled trials,RCTs）。运用RevMan 5.3和Stata 15.0软件进行统计学处理。结果： 最终纳入17篇文献,共35 299例患者,其中1 072例2型糖尿病患者罹患恶性肿瘤。Meta分析结果表明,与对照组相比,SGLT2抑制剂与总体肿瘤风险增加无显著相关性（RR=0.98,95% CI：0.96~1.36）。不同SGLT2抑制剂对肿瘤发生的风险无显著相关性（RR=0.92,95% CI：0.81~1.04）。结论： 目前来自短期随机对照试验的证据并未表明使用SGLT2抑制剂的2型糖尿病患者有增加发生恶性肿瘤的风险。     

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。     

钠–葡萄糖协同转运蛋白2抑制剂对心肌梗死影响的研究进展

钠–葡萄糖协同转运蛋白2(SGLT2)抑制剂是近年来应用于临床的新型口服抗糖尿病药物,主要通过抑制分布在肾脏肾小管处的SGLT2来阻止多余葡萄糖的重吸收,促进尿糖排泄,从而降低循环血糖水平,同时发挥利钠、利尿作用,对充血性心力衰竭也是一种新的治疗选择。随着越来越多的人群受用,研究发现SGLT2抑制剂还具有降低心血管结局等多种心血管保护作用,不仅可使心衰患者受益,对心肌梗死也呈现出多效性,尽管相关机制目前只是推测。主要对SGLT2抑制剂治疗心肌梗死的相关研究进行综述。     

钠-葡萄糖共转运蛋白2抑制剂降糖及降糖外作用研究进展

钠-葡萄糖共转运蛋白2(SGLT2)抑制剂可减少肾小管重吸收葡萄糖,降低高血糖引起的病理性葡萄糖肾阈值,促进尿糖排泄,是2型糖尿病(T2DM)口服降糖药中的后起之秀。SGLT2抑制剂还有着诸多降糖外作用,如保护心脏和肾脏、改善机体能量代谢、改善睡眠呼吸暂停综合征、延缓非酒精性脂肪肝病进展、减轻炎症反应、抑制交感神经激活等。基于SGLT2抑制剂的降糖及降糖外多重作用,使其不仅用于T2DM,也越来越广泛地用于心血管不良事件及慢性肾病的治疗。然而,SGLT2抑制剂在使用过程中仍需关注其潜在风险,加强药物治疗监护,提高安全性和有效性。     

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。     

二肽基肽酶4抑制剂和钠-葡萄糖转运蛋白2抑制剂 联合治疗2型糖尿病的临床应用进展

DPP-4抑制剂与SGLT2抑制剂联合治疗,可以在减轻副作用的基础上更加有效地降低2型糖尿病患者的血糖,但是对于不同剂量的组合,仍需大量临床试验以评估其临床疗效和安全性,使临床医生根据T2DM病人的具体情况选择治疗药物的组合。     

钠-葡萄糖协同转运蛋白2抑制剂防治糖尿病肾病的临床研究进展

糖尿病肾病是糖尿病的微血管并发症,随着病情的发展可出现终末期肾病,对患者的生命安全构成极大威胁.在临床中,糖尿病肾病的临床治疗难度大,故该疾病的防治成为了临床所关注的重点内容.近年来,一种新型降糖药物——钠-葡萄糖协同转运蛋白2抑制剂(SGLT-2i)的出现,给糖尿病肾病的防治带来了新的契机.SGLT-2i不仅能降低患...     

Real-world impact of glycated hemoglobin reduction on treatment intensification and glycated hemoglobin goal attainment in type 2 diabetes mellitus patients initiated on a sodium glucose co-transporter 2 (SGLT2) inhibitor (SGLT2i)

Objective: To evaluate the impact of a 0.2% reduction in glycated hemoglobin (HbA1c) on treatment intensification, poor HbA1c control and HbA1c goal attainment in patients with type 2 diabetes mellitus (T2DM) initiated on a sodium glucose co-transporter 2 (SGLT2) inhibitor (SGLT2i).

Methods: IQVIATM Health Plan Claims Data – US and IQVIATM Ambulatory EMR Data – US databases (29 October 2012–31 March 2016) were used to identify adults with T2DM initiated on an SGLT2i (index date) who had HbA1c measurements pre- and post-index, and ≥6?months of eligibility pre-index (baseline). HbA1c change was defined as the difference between the first post-index and the last pre-index measurements. Cox regression models were used to assess treatment intensification, poor HbA1c control (i.e. HbA1c?>?9%, among patients <9% at baseline) and goal attainment (HbA1c?<?7%, <8%; among patients with HbA1c above goal at baseline) adjusting for HbA1c change and baseline characteristics. Patients were observed up to one year after the first HbA1c measurement or end of eligibility. Hazard ratios (HRs) and 95% confidence intervals (CIs) were reported.

Results: A total of 938 patients (mean age 54.9, 42.5% female, mean HbA1c 8.5%) were selected. Following SGLT2i initiation, each 0.2% reduction in HbA1c levels was associated with a decreased risk of treatment intensification (HR [95% CI]?=?0.90 [0.86–0.92]), a decreased likelihood of reaching HbA1c?>?9% (HR [95% CI]?=?0.85 [0.79–0.88]) and higher likelihoods of achieving a treatment goal of HbA1c?<?7% (HR [95% CI]?=?1.17 [1.12–1.21]) and HbA1c?<?8% (HR [95% CI]?=?1.08 [1.04–1.10]).

Conclusions: In T2DM patients, each HbA1c reduction of 0.2% following the initiation of an SGLT2i was associated with a significant positive impact on treatment intensification and HbA1c goal attainment.     

Canagliflozin:治疗2型糖尿病的新型钠-葡萄糖共转运体2抑制剂

钠-葡萄糖共转运体2(SGLT2)是近年来新发现的2型糖尿病治疗靶点。抑制SGLT2可减少肾脏葡萄糖的重吸收,增加尿糖排出,从而降低血糖。Canagliflozin是SGLT2抑制剂,可结合饮食控制和运动来改善成人2型糖尿病的血糖。Canagliflozin的推荐剂量为100 mg,口服,每日1次。临床试验表明canagliflozin治疗2型糖尿病安全有效,耐受性好。     

Effectiveness and safety of sodium–glucose co-transporter-2 inhibitors in Thai adults with type 2 diabetes mellitus: a real-world study

Abstract

Background

Sodium–glucose co-transporter-2 inhibitors (SGLT2is) are widely used to improve both glycemic control and cardio-renal outcomes. We aim to evaluate the real-life clinical effectiveness, safety and outcomes of SGLT2is in Thai adults with type 2 diabetes mellitus (T2DM).     

Level of glycemic control among US type 2 diabetes mellitus patients on dual therapy of metformin and sodium–glucose cotransporter 2 inhibitor: a retrospective database study

Abstract

Objective

To assess the level of glycemic control among type 2 diabetes patients on sodium-glucose cotransporter 2 inhibitor (SGLT2i) and metformin dual therapy.     

老年2型糖尿病患者糖化血红蛋白与空腹血糖和血脂相关性研究

目的:探讨老年2型糖尿病患者糖化血红蛋白(HbA1c)与空腹血糖(FPG)、血脂的相关性及其意义。方法:对61例老年2型糖尿病患者(糖尿病组)及60例健康老年体检者(对照组)进行HbA1c、FPG、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、载脂蛋白A1(ApoA1)、载脂蛋白B(ApoB)测定,对HbA1c及FPG、血脂进行相关性分析。结果:糖尿病组HbA1c,FPG,TC,TG,LDL-C,ApoB明显高于对照组;糖尿病组HDL-C和ApoA1明显低于对照组,HbA1c与FPG,TC,TG,LDL-C,ApoB呈正相关,与HDL-C和ApoA1呈负相关,差异均有统计学意义(P<0.05)。结论:老年糖尿病患者HbA1c与FPG、血脂均有一定的相关性。联合检测HbA1c,FPG和血脂水平对老年糖尿病患者诊断及治疗具有重要意义。     

Empagliflozin,a sodium glucose co-transporter 2 inhibitor,in the treatment of type 1 diabetes

Introduction: Available anti-hyperglycemic therapy in type 1 diabetes (T1DM) is currently restricted to insulin, pramlintide, and pancreas or islet cell transplantation. The imperfect replication of normal insulin secretion and glucose control has been a driver for development of other anti-hyperglycemic agents for this population. Empagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, is currently under investigation as an add-on therapy to insulin in T1DM.

Areas covered: Within the drug evaluation, the authors describe the mechanism of action of SGLT2 inhibitors and preliminary results from studies investigating treatment in rodent models and in individuals with T1DM.

Expert opinion: Studies on adjunct therapeutic effects of empagliflozin in individuals with T1DM are limited, but initial reports show favorable effects on reducing HbA1c, body weight, total daily insulin dose and hypoglycemic events. Intriguingly, this drug may confer a degree of renal protection by reducing glomerular hyperfiltration that can arise in the diabetic state. Currently, the primary concern seems to be the presence of ketone levels indicating an under-insulinized state. Long-term effects can only be inferred from studies in type 2 diabetes mellitus at this time. Empagliflozin represents a novel non-insulin-mediated therapy that warrants further investigation.     

Sodium glucose co-transporter 2 inhibitor luseogliflozin in the management of type 2 diabetes: a drug safety evaluation

Introduction: Sodium glucose co-transporter-2 (SGLT2) inhibitors have been developed recently as a new class of anti-diabetic drug, and are becoming widely used in the management of type 2 diabetes (T2D). As these agents have a considerably different glucose-lowering mechanism from those of other anti-diabetic drugs, safe use of this drug class needs to be discussed based on data available from preapproval clinical trials as well as real-world studies. The SGLT2 inhibitor luseogliflozin was developed by Taisho Pharmaceutical Co., Ltd. and was approved as an oral anti-diabetic drug for T2D in Japan

Areas covered: The overall safety and efficacy of SGLT2 inhibitor luseogliflozin are summarized on the basis of a literature review, with a focus on reported adverse drug reactions in preapproval clinical trials and a post-marketing surveillance.

Expert opinion: SGLT2 inhibitor luseogliflozin is well tolerated, significantly improves hyperglycemia in preapproval clinical trials, and has a favorable safety profile in both preapproval clinical trials and post-marketing surveillance in elderly patients. While long-term safety and efficacy remain to be seen, luseogliflozin can benefit T2D patients worldwide. However, healthcare professionals must perform appropriate patient education that includes temporary withdrawal of luseogliflozin during patient a ‘sick day’ and avoidance of strict carbohydrate restriction during luseogliflozin treatment.     

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。     

Luseogliflozin for the treatment of type 2 diabetes

Introduction: Sodium glucose cotransporter 2 (SGLT2) inhibitors are expected to provide adequate glycemic control, and be safe and well tolerated, for treating type 2 diabetes mellitus (T2DM). Luseogliflozin is a highly selective SGLT2 inhibitor that was recently approved for marketing and launched in Japan to treat T2DM.

Areas covered: This review summarizes the published data regarding the mechanism of action, clinical efficacy, and safety of luseogliflozin for treating T2DM. Other potential benefits of luseogliflozin, including lowering body weight and blood pressure, beyond its glucose-lowering effects are also discussed.

Expert opinion: Luseogliflozin lowers plasma glucose concentration and body weight, and has beneficial effects on other clinically relevant parameters, including blood pressure and uric acid, in patients with T2DM. Although it had a good safety profile in clinical trials, there may be some safety concerns, including a possible decrease in muscle mass and an increase in ketone bodies. Therefore, careful administration and consideration of its benefit–risk balance are necessary. When using luseogliflozin, it is important to select appropriate patients and to adhere to its guidelines for use. If used correctly, luseogliflozin is expected to be positioned as a new type of oral hypoglycemic drug for treating T2DM.     

阿卡波糖联合诺和锐30治疗2型糖尿病血糖控制欠佳患者的疗效观察

目的 探讨阿卡波糖联合诺和锐30治疗2型糖尿病血糖控制欠佳者的临床疗效。方法 南京大学医院收治的52例血糖控制欠佳的2型糖尿病患者随机分为治疗组（27例）和对照组（25例）。对照组给予诺和锐30注射液,2次/d,早晚餐前皮下注射。治疗组于三餐前口服阿卡波糖片,50 mg/次,3次/d,诺和锐30注射液的用法同对照组。治疗12周后,比较两组患者治疗前后空腹血糖（FBG）、餐后2 h血糖（2 h PG）、糖化血红蛋白（HbA1c）、体质量指数（BMI）、血脂变化情况及胰岛素用量。结果 治疗后,两组患者FBG、HbA1c均较治疗前明显降低,治疗前后差异有统计学意义（P<0.05）。治疗后,治疗组患者HbA1c水平明显低于对照组,两组比较差异有统计学意义（P<0.05）。治疗后,两组全天七点血糖水平均较治疗前明显降低,同组治疗前后差异有统计学意义（P<0.05）;同时,治疗组三餐后2 h PG均显著低于对照组,两组比较差异有统计学意义（P<0.05）。治疗组血糖达标时间明显短于对照组,两组比较差异有统计学意义（P<0.05）。结论 阿卡波糖联合诺和锐30治疗血糖控制欠佳的2型糖尿病患者具有较好的临床疗效,可有效控制餐后血糖水平,具有良好的临床应用价值。