BARCELONA (EGMN) – Four widely prescribed oral sulfonylurea drugs are associated with significantly increased risk of all-cause mortality, compared with metformin in type 2 diabetic patients having a history of MI, according to a comprehensive Danish national cohort study.

The study included all Danish adults with a prior MI who started on oral glucose-lowering monotherapy during 1997-2006. The conclusion: Glimepiride, glyburide, glipizide, and tolbutamide were associated with 33%-43% higher mortality risk than was metformin, Dr. Tina Ken Schramm said at the annual congress of the European Society of Cardiology.

In contrast, single-agent gliclazide and repaglinide had all-cause mortality risks similar to metformin.

“The clinical implication of this is that metformin, gliclazide, and repaglinide appear superior to other single-drug treatments received. We believe that metformin in general should be part of the treatment of type 2 diabetes to reduce mortality, but gliclazide and repaglinide may be good alternatives,” said Dr. Schramm of the Heart Center at Copenhagen University National Hospital.

Metformin deserves the nod as the first-line agent on the basis of the results of the landmark United Kingdom Prospective Diabetes Study, which convincingly established the drug as the safest glucose-lowering agent available, she added.

Out of the total Danish population of roughly 4.1 million, 107,870 type 2 diabetic individuals initiated monotherapy with a glucose-lowering agent during the 9-year study period. Among them were 9,135 with a prior MI, who formed the population for this study.

Glimepiride was the most widely prescribed of the glucose-lowering medications in Denmark, being used by 43% of subjects. Next came metformin (32%), glyburide (13%), glipizide and gliclazide (7% each), tolbutamide (6%), and repaglinide (2%). Acarbose was prescribed as monotherapy in only 44 patients nationwide – far too small a number to allow meaningful results. Similarly, the thiazolidinediones, which in Denmark are not recommended therapy in this clinical setting, were used too seldom to draw any conclusions, Dr. Schramm explained.

Metformin served as the comparator in determining all-cause mortality risks for the other oral glucose-lowering agents in a multivariate analysis adjusted for age, gender, years of diabetes, cardiovascular medications, and socioeconomic status.

Audience members asked if confounding was a potential issue in the study – that is, perhaps patients on drugs other than metformin were sicker, or had previously been on metformin but proved intolerant or unresponsive to it. Dr. Schramm replied that it’s unlikely, since when she performed a subanalysis restricted to those patients starting their first-ever glucose-lowering agent the results were unchanged.

She undertook the study because most prior studies of oral glucose-lowering medications did not look beyond glucose-lowering efficacy in terms of outcomes.

Dr. Schramm reported having no financial conflicts of interest regarding the study.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

巴塞罗那(EGMN) ——丹麦开展的一项全国性综合队列研究显示，在既往有心肌梗死(MI)病史的2型糖尿病患者中，相对于二甲双胍，4种常用口服磺脲类药物可显著增加患者的全因死亡风险。

 

在今年的欧洲心脏病协会年会上，Tina Ken Schramm博士报告称，该研究纳入了1997~2006年间既往有MI病史且开始接受口服降糖药单药治疗的所有丹麦成年患者。研究得出的结论是：与二甲双胍相比，格列美脲、格列本脲、格列吡嗪和甲苯磺丁脲使患者的死亡风险上升了33%~43%。

 

而服用单药格列齐特或瑞格列奈的患者的全因死亡风险与服用二甲双胍的患者相似。

 

丹麦哥本哈根大学国立医院心脏中心的Schramm博士指出，“该结论的临床意义是二甲双胍、格列齐特和瑞格列奈可能优于其他单药治疗。我们认为二甲双胍通常都应作为2型糖尿病治疗的一部分以降低死亡率，但格列齐特和瑞格列奈也可能是很好的选择。”

 

Schramm博士补充道，基于具有划时代意义的英国前瞻性糖尿病研究的结果，二甲双胍的确应该作为一线治疗药物，现已充分证实它是目前最安全的降糖药。

 

在大约410万的丹麦总人口中，107,870名2型糖尿病患者在这9年的研究期限内开始了某种降糖药的单药治疗。其中9,135名既往有MI病史，这部分患者即为该研究的受试人群。

 

Schramm博士解释道，在丹麦，格列美脲是最常用的降糖药，有43%的受试者都是服用的格列美脲。其次分别是二甲双胍(32%)、格列本脲 (13%)、格列吡嗪和格列齐特(各占7%)、甲苯磺丁脲(6%)以及瑞格列奈(2%)。全国仅有44名患者将阿卡波糖作为单药治疗，人数太少无法得出有意义的结果。同样，噻唑烷二酮类药物由于在丹麦并非2型糖尿病的推荐用药，因此服用人数过少也难以得出结论。

 

将二甲双胍作为对照药物，根据患者年龄、性别、糖尿病病程长短、心血管药物治疗以及社会经济状况进行校正的多因素分析，以比较其他口服降糖药的全因死亡风险。

 

参会代表提出该研究是否存在潜在的混杂因素，即是否有可能服用除二甲双胍以外的其他药物的患者病情更重，或者曾经服用过二甲双胍但后来发现不耐受或无应答。Schramm博士回答道，这种可能性不大，因为她还针对第一次开始服用降糖药的患者进行了亚分析，仍得出了相同的结果。

 

Schramm博士之所以开展这项研究，是因为之前针对口服降糖药的研究大多只关注药物的降糖效果，而忽视了患者结局。

 

Schramm博士声明无任何与该研究相关的经济利益冲突。

 

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