糖复康宁提取物对2型糖尿病大鼠的降糖作用研究

目的 研究中药复方糖复康宁提取物2糖尿病模型大鼠的降血糖作用。方法 分别以遗传性ZDF模型大鼠和链脲佐菌素（STZ）联合高糖高脂饲料诱导的SD大鼠为此次研究的2型糖尿病模型动物,ig给予低、高剂量（5.0、10.0 g生药/kg）的糖复康宁提取物,金芪降糖片（455 mg/kg）作为阳性药,连续给药42 d,每周测定空腹血糖、给药第38天测定葡萄糖耐量。结果 ZDF模型结果显示,模型组大鼠血糖值波动幅度保持在10%以内,显著高于对照组（P<0.01）;给药42 d后,与模型组比较,各给药组血糖均显著下降（P<0.01）,金芪降糖片及糖复康宁提取物低、高剂量组血糖下降率分别为（35.9±8.4）%、（22.1±11.1）%、（50.0±9.1）%;STZ模型结果显示,模型组大鼠血糖一直维持在较高水平（21.1~21.6 mmol/L）,变化幅度相对稳定,显著高于对照组（P<0.01）;给药42 d后,与模型组比较,各给药组血糖均下降,其中糖复康宁提取物低、高剂量组差异显著（P<0.01）;金芪降糖片及糖复康宁提取物低、高剂量组血糖下降率分别为（18.6±5.7）%、（21.6±7.2）%、（51.7±20.2）%。糖复康宁提取物低、高2个剂量组血糖曲线下面积（AUC）与模型组比较均显著下降（P<0.05、0.01）。结论 中药复方糖复康宁对2种2型糖尿病模型均发挥显著降糖效果。     

一类全新机制的2型糖尿病治疗药物SGLT2抑制剂

钠-葡萄糖协同转运蛋白(SGLT2)抑制剂是一类作用于新靶点的降糖药物,目前已进入临床使用,美国FDA已经批准上市的有6种,中国CFDA也相继批准了达格列净(dapagliflozin)及恩格列净(empagliflozin)在我国上市。为了使临床医师及药师更好地了解和使用该类全新机制的糖尿病治疗药物,本文从该类药物的来源、化学结构、药理作用机制、药物代谢动力学特点、临床疗效与应用、不良反应及安全性进行了综述,以供参考。     

基于SGLT2受体蛋白的新型糖尿病药物的研究进展

目的钠-葡萄糖共转运蛋白2(SGLT2)是肾小管上负责将尿糖重新吸收为血糖的重要转运蛋白,对该蛋白的抑制可以使糖从血液中转移进入尿液。本文总结了目前各大药物公司在研的SGLT2抑制剂的构效关系及其临床研究进展。方法综述了近年来国内外相关报道,对O,C,N-糖苷类和非糖苷类SGLT2抑制剂的药理、药效和药代学进行讨论,并就其临床研究及开发上市状况进行概述。结果 SGLT2抑制剂的结构与其药理活性和代谢稳定性间的关系是该类药物研发的重点。结论 SGLT2抑制剂与降糖作用的构效关系,对开发新一代治疗糖尿病药物具有重要意义。     

地黄不同方法提取物制剂降糖作用的实验研究

水煎煮中药是中成药生产中最常用的提取方法 ,亦符合传统中医用药习惯。我们的研究表明 ,地黄、黄芪、丹参配伍的中药复方具有改善糖尿病患者的症状和一定的降糖作用[1、2 ] 。鉴于地黄水煮提取物的量很大 ,超出生药干重量的 5 0 % ,不适用于制成胶囊剂。为了减少地黄提取物的总量 ,而又不影响其效果 ,我们观察了地黄水提、醇提及水醇法提取物制剂对小鼠肾上腺素诱发高血糖的降糖作用 ,以寻找合适工艺。1　材料与方法1.1　药物　全部中药材购自贵阳市药材公司。 (1)丹参水煮二次 ,第一次 2h ,第二次 1h ,过滤 ,合并滤液 ,浓缩至相对密度为 1…     

鬼针草提取物对糖尿病大鼠降糖活性的初步观察

目的研究鬼针草乙酸乙酯提取物的降糖活性。方法注射链脲佐菌素建立大鼠糖尿病模型,观察鬼针草乙酸乙酯提取物对血糖值的影响。结果鬼针草乙酸乙酯提取物能显著降低糖尿病大鼠的血糖值。结论鬼针草乙酸乙酯提取物有显著的降糖活性。     

SGLT2抑制剂引起酮症酸中毒的机制及处理

钠-葡萄糖协同转运蛋白-2（SGLT2）抑制剂是一类新型的降糖药物,通过抑制肾小管对葡萄糖的重吸收降低血糖。但临床中发现SGLT2抑制剂可导致血糖不明显升高的酮症酸中毒。本文就SGLT-2抑制剂引起酮症酸中毒的发生机制及处理措施进行了综述。     

多种降糖植物提取物的研究进展

目的介绍具有降血糖作用的植物提取物的最新进展,为研制开发新药提供参考。方法查阅降血糖植物提取物研究的相关文献,并加以归纳和整理。结果苦瓜、当归、桑叶等的提取物有较显著的降血糖作用,其降血糖作用机制的研究涉及葡萄糖的代谢、胰岛素及其受体水平等多个环节。结论还应加强对其活性物质的分析和研究,进一步明确其功效及作用机制,开发出有效的中药及中成药来预防并治疗糖尿病。     

SGLT1/SGLT2双重抑制剂——Sotagliflozin的研究概况

钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂是一类治疗糖尿病的新型药物。SGLT2抑制剂的研发一直致力于相对钠-葡萄糖协同转运蛋白1(SGLT1)高度选择性抑制SGLT2。然而,动物基因组学和药理学研究表明抑制肠道SGLT1也可能成为治疗糖尿病药物靶点。Sotagliflozin是一种SGLT1/SGLT2双重抑制剂,具有独特的非胰岛素依赖型降糖机制,通过抑制SGLT1而减少经胃肠道入血的葡萄糖,也通过抑制SGLT2而增加葡萄糖的排出发挥作用。本文重点综述了其有效性和安全性。     

SGLT2抑制剂在糖尿病患者中的临床应用进展

钠—葡萄糖协同转运蛋白2(SGLT2)是一种新颖的降血糖药物,降低血糖的作用是通过阻断肾脏对尿中葡萄糖的重吸收。越来越多的临床研究发现其降糖效果明显,同时能改善患者的血脂、BMI、收缩压等。但在一些研究中发现其可能导致生殖器及尿道感染风险,同时增加骨折及酮症酸中毒的发生率。本文对SGLT2治疗糖尿病患者的机制及安全性、代谢调控、心血管和肾脏保护作用等方面进行研究进展的综述。     

SGLT2抑制剂对血尿酸影响的研究进展

新型降糖药物钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂在降糖的同时不仅可改善2型糖尿病患者心血管及肾脏结局,亦可降低血尿酸水平,机制可能与增加尿糖排泄及渗透性利尿有关.本文就SGLT2抑制剂研究现状及对血尿酸影响机制、特点、获益等几个方面进行综述,旨在为高尿酸血症患者的治疗提供参考.     

An update of SGLT1 and SGLT2 inhibitors in early phase diabetes-type 2 clinical trials

Introduction: More than 424 million adults have diabetes mellitus (DM). This number is expected to increase to 626 million by 2045. The majority (90–95%) of people with DM has type 2-diabetes (T2DM). The continued prevalence of DM and associated complications has prompted investigators to find new therapies. One of the most recent additions to the anti-diabetic armamentarium are inhibitors of sodium-glucose co-transporters 1 and 2 (SGLT1, SGLT2).

Areas covered: The authors review the status of SGLT2 inhibitors for the treatment of T2DM and place an emphasis on those agents in early phase clinical trials. Data and information were retrieved from American Diabetes Association, Diabetes UK, ClinicalTrials.gov, PubMed, and Scopus websites. The keywords used in the search were T2DM, SGLT1, SGLT2, and clinical trials.

Expert opinion: The benefits of SGLT inhibitors include reductions in serum glycated hemoglobin (HbA1c), body weight, blood pressure and cardiovascular and renal events. However, SGLT inhibitors increase the risk of genitourinary tract infections, diabetic ketoacidosis, and bone fractures. The development of SGLT inhibitors with fewer side effects and as combination therapies are the key to maximizing the therapeutic effects of this important class of anti-diabetic drug.     

SGLT2抑制剂Canagliflozin——Ⅱ型糖尿病治疗的新药

钠依赖的葡萄糖转运蛋白2(sodium-dependent glucose transporters 2,SGLT2)是一种低亲和力、高容量的转运体,主要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。因此,抑制SGLT2,阻止近曲小管对葡萄糖的重吸收,通过增加尿糖的排出来降低血糖已经成为糖尿病治疗的一种新的策略。文章简述了目前处于临床阶段的SGLT2抑制剂,重点阐述了第1个被FDA批准的SGLT2抑制剂——Canagliflozin,包括它的合成、药动学、药效学、临床研究及不良反应等。     

SGLT2 inhibitors for the treatment of diabetes: a patent review (2013-2018)

Introduction: The sodium-glucose co-transporter 2 (SGLT2) is ascribed to target renal tubular glucose re-absorption, and its inhibition has been proved to induce glucosuria which improves the glycemic index. Accordingly, SGLT2 inhibitors have found to be the promising class of antidiabetic agents for the management of type 2 diabetes mellitus. A large number of SGLT2 inhibitors have developed through structural modification and investigated for their ability to selectivity inhibit SGLT2 transporters with better bioavailability.

Areas covered: This review comprises a summary of patent applications (2013–2018) of SGLT2 inhibitors with focus on chemical structural advancement and therapeutic potentials in the management of diabetes and related disorders.

Expert opinion: SGLT2 inhibitors exert multiple metabolic benefits, including reduced glycated hemoglobin (HbA1c), improved glycemic control (fasting and postprandial), reduced body weight, reduced systolic and diastolic blood pressure and improved HDL cholesterol. Due to the virtue of no interference with insulin action and secretion, their efficacy remains the same even in presence of progressive β cell failure in type 2 diabetes. Additionally, few members of this class have been reported to exhibit cardioprotective, renoprotective, and anticancer activity. However, more study on the long-term outcomes in patients taking SGLT2 inhibitors is warranted.     

Remogliflozin etabonate: a novel SGLT2 inhibitor for treatment of diabetes mellitus

Introduction: Inhibitors of sodium-glucose co-transporter type 2 (SGLT2) represent a new class of anti-hyperglycemic agents with a unique mechanism of action. These drugs lower blood glucose by increasing urinary glucose excretion. Remogliflozin etabonate (RE) is a prodrug of remogliflozin, an SGLT2 inhibitor under development.

Areas covered: The following article reviews all of the clinical studies published regarding metabolism, drug interaction, safety and efficacy of RE in healthy subjects, patients with type 1 and type 2 diabetes.

Expert opinion: Available data suggest low potential for RE to interact with other drugs affecting the P450 system. Compared with placebo, RE reduces hemoglobin A1c (HbA1c) levels by an average of 0.5 – 1.0% after 12 weeks of therapy in drug-naive patients with type 2 diabetes. Because of its relatively short half-life, RE may be slightly more effective when used twice daily than once daily. One preliminary study also showed that RE decreased plasma glucose levels in type 1 diabetes. Advantages of RE include modest weight loss of ～ 2 kg, low risk of hypoglycemia, and a trend toward decrease in blood pressure. The commonest adverse effects of RE are genital mycotic infections, urinary tract infections, and dizziness. However, further studies are needed to establish its long-term safety and efficacy, and to determine whether it has specific advantages over currently approved SGLT2 inhibitors.     

Better response to the SGLT2 inhibitor dapagliflozin in young adults with type 2 diabetes

Background and aim: A variation of the response to Sodium glucose co-transporter 2 (SGLT2) inhibitors with age has not been investigated in patients with diabetes. The aim of this study was to assess renal threshold of glucose (RTg) before and after administration of an SGLT2 inhibitor in young adult patients (≤40 years) and older adult patients (>40 years) with type 2 diabetes (T2DM). Subjects and methods: Twenty Japanese patients with T2DM were enrolled. Baseline data were obtained on the first day and dapagliflozin (5 mg) was administered at 6:00 on the second day. Glucose excursions were assessed by continuous glucose monitoring and urine samples were collected every hour during the daytime (7:00 to 15:00) on both days. RTg was estimated from the regression line of the scatter plot of the hourly mean glucose concentrations. Results: After a single dose of dapagliflozin, RTg decreased from 121.5 to 6.1 mg/dl in the young adult group and from 151.0 mg/dl to ?15.8 mg/dl in the older group. After dapagliflozin, the slope of the regression line was significantly steeper in the young adult group. Conclusion: Dapagliflozin was more effective in young patients because they showed a larger response of urinary glucose excretion.     

SGLT2 inhibition: efficacy and safety in type 2 diabetes treatment

Introduction: Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) offer a new opportunity for the management of type 2 diabetes mellitus. These agents reduce hyperglycemia by decreasing the renal glucose threshold and thereby increasing urinary glucose excretion. Subsequent reduction of glucotoxicity improves beta-cell sensitivity to glucose and tissue insulin sensitivity.

Areas covered: This article analyzes the efficacy and safety data of canagliflozin, dapagliflozin and empagliflozin in randomized controlled trials of 24 – 104 weeks duration, compared with placebo or an active comparator, in patients treated with diet/exercise, metformin, dual oral therapy or insulin.

Expert opinion: SGLT2 inhibitors significantly and consistently reduce glycated hemoglobin, with a minimal risk of hypoglycemia. The improvement of glucose control is similar or slightly better compared with metformin, sulfonylureas or sitagliptin, with the add-on value of significant reductions in body weight and blood pressure. However, caution is recommended in fragile elderly patients and patients with chronic kidney disease. An increased risk of genital mycotic infections is observed, but urinary tract infections are rare. Concern about an unexpected risk of euglycemic ketoacidosis has been recently reported. A possible renal protection deserves further attention. A remarkable reduction in cardiovascular mortality was reported in EMPA-REG OUTCOME with empagliflozin.     

SGLT2抑制剂LX4211的合成方法研究

目的研究SGLT2抑制剂LX4211的合成方法。方法以L-(-)-木糖为起始原料,经羟基保护、氧化、酰胺化得到中间体(5S)-1-C-4-吗啉基-4,5-O-异亚丙基-D-2,5-呋喃木糖二醛,该中间体与5-溴-2-氯-4'-甲氧基二苯甲烷缩合,再经还原、脱保护、开环扩环、酯化、溴代、硫醚化、醇解得到目标化合物LX4211。结果与结论优化并确定了LX4211的合成路线,总收率由18.1%提高至23.2%(以L-(-)-木糖计),其结构经1H-NMR和MS确证。该路线成本较低、操作简便、条件温和、收率高,具有工业化生产的潜力。     

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。