磺脲类降糖药的前世今生

治疗糖尿病的药物主要包括口服降糖药和胰岛素，绝大多数2型糖尿病患者在他们一生的大部分时间里都会应用口服降糖药。目前，口服降糖药主要有四大类：胰岛素促泌剂、双胍类、噻唑烷二酮类和α－糖苷酶抑制剂，其中仅有胰岛素促泌剂可以促进内源性胰岛素分泌，纠正糖尿病发生、发展的主要病理机制，     

胰岛β细胞功能保护与理想的胰岛素促泌剂

2型糖尿病的发病原因主要是胰岛素抵抗和胰岛素分泌障碍。 2 0 0 3年底对新型胰岛素促泌剂—那格列奈举行了专题讨论会。那格列奈是来源于氨基酸 (D 苯丙氨酸 )的胰岛素促泌剂 ,其促胰岛素分泌呈血糖依赖性 ,可有效控制高血糖症和减少空腹低血糖的发生率 ,防止对 β细胞的过度刺激和保护胰岛功能。那格列奈是一种新型的治疗 2型糖尿病的药物。     

磺脲类药物不同人群的不同用法

磺脲类药物属于胰岛素促泌剂,与其他口服降糖药相比,磺脲类药物的降糖效果最强。应用磺脲类药物的患者的血糖达标率明显高于服用二甲双胍和饮食控制的患者,因此在多个治疗指南中被推荐为非肥胖2型糖尿病患者的一线用药,也可与其他药物联合使用治疗肥胖的2型糖尿病,一般不和另一种胰岛素促泌剂格列奈类药物合用。具体来说,在不同的人群应用磺脲类药物,用法有所不同。     

吡格列酮在糖尿病中的地位及其临床应用

抗糖尿病药物种类较多,它包括降血糖药物(如胰岛素促泌剂和胰岛素)和抗高血糖药物(如双胍类、糖苷酶抑制剂和噻唑烷二酮衍生物等),其中噻唑烷二酮衍生物(或称格列酮类药物:TZD)是近年来新开发的并己在临床得到广泛应用的唯一可直接改善胰岛素抵抗的一线抗高血糖药物和基础用药,TZDs的使用可贯穿于2型糖尿病的不同病理生理阶段.     

吡格列酮在糖尿病中的地位及其临床应用

抗糖尿病药物种类较多，它包括降血糖药物（如胰岛素促泌剂和胰岛素）和抗高血糖药物（如双胍类、糖苷酶抑制剂和噻唑烷二酮衍生物等），其中噻唑烷二酮衍生物（或称格列酮类药物：TZD）是近年来新开发的并己在临床得到广泛应用的唯一可直接改善胰岛素抵抗的一线抗高血糖药物和基础用药，TZDs的使用可贯穿于2型糖尿病的不同病理生理阶段。     

格列奈类促泌剂的临床认识

格列奈类促泌剂是国内常用的非磺脲类胰岛素促泌剂,主要包括瑞格列奈和那格列奈。文章将从其在国内外的应用、降糖效果、不良反应、与胰岛素的合用、在CKD中的使用以及用药原则等方面阐述对格列奈类药物的临床认识。     

胰岛素促泌剂与胰岛素增敏剂有何异同？

我们知道，2型糖尿病的基本病理机制就是胰岛素分泌不足和胰岛素抵抗，而口服降糖药主要是针对上述两大机制而设计的，分为胰岛素促泌剂和胰岛素增敏剂。[第一段]     

消渴丸联合二甲双胍治疗糖尿病的临床体会

现行的糖尿病防治指南指出,为了降低并发症的发病风险,达到控制血糖的目标,进行早期强化治疗是非常必要的,尤其提倡以早期联合应用口服降糖药物取代逐渐递增给药的传统方案。联合用药可尽快降低高血糖,减轻胰岛素抵抗,最大限度地保护B细胞功能并延缓其衰退。2型糖尿病患者可首选胰岛素促泌剂,     

长期使用胰岛素促泌剂，会使自身胰岛分泌功能减退吗？

我今年67岁,患2型糖尿病11年了。5年前,因为口服降糖药已经不能控制血糖了,于是我在医生的指导下更改了治疗方案,开始注射胰岛素。可最近血糖值忽高忽低,经医生指导添加了胰岛素促泌剂。我想请问专家：是不是患病时间长了就必须要打胰岛素,增加促泌剂会使自身胰岛功能减退吗？     

门诊2型糖尿病患者处方降糖药物使用情况研究

目的 探讨门诊2型糖尿病患者处方降糖药物的使用情况。方法 选取2019年10月—2020年10月该院门诊2型糖尿病患者186例的4 261张处方,分析患者的处方降糖药物的情况,统计患者的一般资料,降糖药物的选择和联用情况,用法用量,给药方式以及合并其他疾病相关用药。结果 186例2型糖尿病,男性占比58.60%,女性占比41.40%;2型糖尿病患者降糖药物用药有5种给药方式,双药口服最高（41.94%）,单用非胰岛素降糖药物占比16.67%,双联非胰岛素降糖药物占比42.47%;186例患者中有18例选择胰岛素（9.68%）,其中选择最多的是门冬胰岛素30注射液,口服胰岛素包括二甲双胍、噻唑烷二酮类以及磺脲类促泌剂等,共12个品种。所有处方中,共22例处方不合理（11.83%）,包括2例用药与诊断不符合、4例给药剂量不合理、16例用药频次不合理。结论 临床药师应当对降糖药物的种类选择进行监督与管理,强化患者健康教育和用药宣教。     

Consensus of Chinese experts on strengthening personalized prevention and treatment of type 2 diabetes

Up to now, there has not yet been guidance or consensus from Chinese experts in the field of personalized prevention and treatment of type 2 diabetes. In view of the above, the endocrinology diabetes Professional Committee of Chinese Non-government Medical Institutions Association, the integrated endocrinology diabetes Professional Committee of the integrated medicine branch of Chinese Medical Doctor Association, and the diabetes education and microvascular complications group of the diabetes branch of the Chinese Medical Association organized relevant experts to discuss and reach the "Chinese expert consensus on strengthening personalized prevention and treatment of type 2 diabetes" for reference in clinical practice.     

Lack of the QTc physiologic decrease during cardiac stress test in patients with type 2 diabetes treated with secretagogues

Patients with type 2 diabetes are at increased susceptibility to a prolonged QT interval. Furthermore, insulin secretagogues, drugs used to treat diabetes, may prolong QT interval and provoke arrhythmias. We evaluated whether secretagogues can affect QTc interval during cardiac stress test in 20 patients with type 2 diabetes treated with secretagogues. ECG stress test was performed in all patients. QTc interval was calculated both before cardiac stress test (BCST) and at acme of cardiac stress test (ACST). Diabetic patients treated with secretagogues showed longer QTc-ACST values than those treated with metformin only. QTc-ACST values resulted shorter than QTc-BCST values in control group. Diabetic patients treated with secretagogues showed QTc-ACST values significantly longer than QTc-BCST values. In our study, diabetic patients treated with secretagogues did not show the QTc physiologic decrease that is a protective against arrhythmias. These results suggest to evaluate, in these patients, QT length, even during routine cardiac stress test.     

Practical review of oral antihyperglycemic agents for type 2 diabetes mellitus

This article gives a practical review of the pharmacology, clinical efficacy, safety, dosing, cost, and place in therapy for oral antihyperglycemic agents used in the treatment of type 2 diabetes mellitus. There are 5 classes of oral antihyperglycemic agents available in the United States: sulfonylurea secretagogues, biguanides, alpha-glucosidase inhibitors, thiazolidinediones, and nonsulfonylurea secretagogues. These agents have distinct characteristics that help in their selection for the treatment of type 2 diabetes.     

中国门诊2型糖尿病患者口服药降糖达标状况调查及格列齐特缓释片优化治疗效果分析

目的 评估中国门诊2型糖尿病患者口服药降糖达标的现状,评价格列齐特缓释片[达美康缓释片,施维雅(天津)制药有限公司]一天一次的优化降糖方案的疗效及安全性.方法 在全国20多个城市的54家医院通过义诊调查门诊口服药治疗(3个月以上)的2型糖尿病患者,评估HbA1c≤6.5%的达标率;对未达标患者入组优化治疗,即采用一天一次的格列齐特缓释片治疗替换每日多次服用的促分泌药物(磺脲类或格列奈类药物),治疗3个月后评价其临床疗效及安全性.结果 血糖控制现状调查显示,5 586名2型糖尿病患者的HbA1c为(7.97±2.89)%,达标率为14.1%.1 721例未达标的患者进行优化治疗后,HbA1c从优化前(8.23±4.00)%降为(6.86±2.24)%,平均值下降1.37%(P<0.001),达标率提高为34.1%;空腹血糖从(8.87±4.65)mmol/L下降为(7.13±5.82)mmol/L;餐后2 h血糖从(12.50±4.00)mmoL/L下降为(8.96±3.61)mmol/L;仅有2.6%的患者报告可疑低血糖发生.结论 目前中国门诊口服药治疗的2型糖尿病患者的血糖控制达标率较低;采用每日一次的格列齐特缓释片优化治疗方案,能安全有效地降低血糖,提高HbA1c达标率,对于优化2型糖尿病的管理有重要意义.     

Insulin,Insulin Resistance,Obesity, and Cancer

Epidemiologic studies have proposed a link between obesity, type 2 diabetes, and cancer. The pathophysiologic mechanisms involved in the development of type 2 diabetes, namely hyperinsulinemia and insulin resistance, have also been implicated in cancer development. Patients with type 2 diabetes are reported to have a worse response to cancer chemotherapy, have more complications, and have a poorer prognosis than patients with cancer without diabetes. Studies also have reported that insulin, insulin secretagogues, and metformin may have effects on tumor growth. Given the escalating worldwide prevalence of obesity and type 2 diabetes, their relationship to cancer has generated great interest and research across many fields of medicine.     

Continuation versus discontinuation of insulin secretagogues when initiating insulin in type 2 diabetes

We compared the combined use of basal insulin, metformin and insulin secretagogues with a combination of basal insulin and metformin in patients with type 2 diabetes starting basal insulin analogue therapy. This analysis was part of a 24-week trial, in which 964 insulin-naive patients with type 2 diabetes inadequately controlled on oral agents (including metformin) were randomized to insulin glargine or detemir. Secretagogues were stopped or maintained at the site-investigators' discretion. During the study, 57.6% of patients continued their secretagogue treatment. Compared with patients stopping secretagogues, those who continued experienced significantly more hypoglycaemia and weight gain. Insulin doses, however, were significantly lower: 0.6 ± 0.4 versus 0.8 ± 0.4 U/kg/day (p < 0.001). The difference between groups in mean HbA1c reduction was not statistically significant. In conclusion, in type 2 diabetic patients starting basal insulin analogue therapy, continuing both metformin and secretagogues results in more hypoglycaemia and weight gain and lower insulin doses than only maintaining metformin.     

Glibenclamide and cardio-metabolic risk: a systematic review

The aim of this review is to evaluate the safety and efficacy of glibenclamide for the treatment of type 2 diabetes mellitus, in particular we evaluated glibenclamide effect on cardiovascular risk and metabolic control, and all causes of mortality. A systematic search strategy was developed to identify randomized controlled trials included in both MEDLINE and the Cochrane Register of Controlled Trials using the terms “glibenclamide”, “secretagogues”, “type 2 diabetes”, “adverse events”, “combination therapy”, “cardiovascular risk”. Participants needed to be affected by type 2 diabetes mellitus, the intervention included glibenclamide at any dosage both in monotherapy or in combination with other anti-diabetic drugs. A validated, 3 items scale was used to evaluate the overall reporting quality of the trials selected for inclusion in the present review. Monotherapy with the most used insulin secretagogues, including glimepiride, glibenclamide, glipizide, and tolbutamide, seems to be associated with increased mortality and cardiovascular risk compared with metformin, even if gliclazide and repaglinide appear to be associated with a lower risk than other insulin secretagogues. Proper selection of the right patient is very useful to obtain the maximum benefit from sulfonylureas use and to reduce at minimum the risk of hypoglycemia.     

中国成人2型糖尿病预防的专家共识精要

2型糖尿病及其并发症导致严重医疗支出与社会公共卫生问题,有效预防2型糖尿病的发生(即其一级预防)是亟待解决且意义重大之事。对此,中华医学会内分泌学分会制定了中国成人2型糖尿病预防的专家共识。文章就该共识推荐的主要内容、血糖谱分类的证据、药物干预的时机和证据进行解读。共识认为应将糖尿病前期血糖谱分为空腹血糖受损,糖耐量低减和空腹血糖受损+糖耐量低减三种;在生活方式干预无效等情况下可考虑药物干预。同时强调生活方式干预是基础,应用药物干预应注意使用条件,必须重视血糖以外的脑心血管病危险因素管理。     

Pathophysiology of type 2 diabetes: rationale for different oral antidiabetic treatment strategies

Type 2 diabetes mellitus is a chronic metabolic disorder that results from defects in both insulin secretion and insulin action. Both insulin resistance and beta-cell failure are genetically determined to some extent; however, environmental factors contribute to exacerbate both abnormalities. Type 2 diabetic individuals are also characterised by reduced beta-cell mass likely due to increased cellular apoptosis. The early use of insulin therapy in type 2 diabetes may prove beneficial to prevent further beta-cell loss and need for exogenous insulin. Treatment options with oral agents are quite diverse, including insulin sensitizers, alpha-glucosidase inhibitors, and beta-cell secretagogues. Although in recent years the emphasis on initial therapy has been shifting from insulin secretagogues to insulin sensitizers such as metformin and thiazolidinediones, questions remain as to genetic and/or phenotypic factors may dictate a different choice of the first antidiabetic drug to be used. It is not totally clear whether monotherapy should be pursued until the maximally effective dose of a given drug or combination therapy should be used to target distinct pathogenic defects in a single patient. Individual phenotypic and genetic characterisation of the patients may help to solve this conundrum, eventually providing tailored treatment algorithms.     

口服降糖药物对2型糖尿病患者心血管结局的影响

改善血糖控制可减少糖尿病患者的心血管并发症,不同药物的作用机制不同,其对心血管结局的影响不同.此外,继2007年对罗格列酮潜在心血管风险的认识之后,陆续开展了大量的前瞻性、随机、对照研究,评估降糖药物对糖尿病患者的心血管系统的影响.传统药物中二甲双胍及噻唑烷二酮类药物对糖尿病患者的心血管系统具有保护作用,但必须警惕噻唑烷二酮类药物可增加心力衰竭的风险;第二代及第三代磺脲类促泌剂及非磺脲类促泌剂并不增加患者心血管事件的发生风险.新型药物中并没有看到二肽基肽酶4抑制剂对心血管系统具有有利或不良影响,是否增加心力衰竭风险目前结果并不统一.而胰高血糖糖素样肽-1受体激动剂及钠-葡萄糖协同转运蛋白2可减少糖尿病患者的心血管疾病风险并降低死亡率;但由于数据有限,仍需要更广泛的研究加以证实.