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两种糖尿病药物可增加骨折风险

Fractures increased with two diabetes drugs

2014-07-18 09:45点击:13857发表评论

旧金山——美国糖尿病学会(ADA)年会上公布的一项涉及99,892例糖尿病成人患者的回顾性研究显示,与使用其他药物治疗糖尿病的患者相比,使用磺酰脲类药物的患者5年内发生骨折的风险高出9%,使用噻唑烷二酮类药物的患者发生骨折的风险也高出9%。

Sandhya Mehta, Ph.D.

这项纵向回顾性分析的数据来自Inovalon公司(一家医疗数据分析公司)旗下的MORE注册库,该公司的Sandhya Mehta医生对这一大型行政理赔数据库2008年~2012年的数据进行分析发现,磺酰脲类药物使用者的骨折发生率为10%,噻唑烷二酮类药物使用者为11%,相比之下,双胍类药物(二甲双胍)使用者为7%,二肽基肽酶-4(DPP-4)抑制剂使用者为8%,氯茴苯酸类似物使用者为11%,肠促胰岛素类似物使用者为6%。在校正混杂因素后,所有其他3种药物的风险比(HR)均为1左右且无统计学显著差异,但磺酰脲类药物的HR增至1.09,噻唑烷二酮类药物的HR增至1.4。

在整个队列中,7%的患者发生骨折。约15%的患者使用磺酰脲类药物,3%使用噻唑烷二酮类药物,78%使用二甲双胍,3%使用DPP-4抑制剂,1%使用肠促胰岛素类似物,1%使用氯茴苯酸类。

Mehta医生表示,既往研究已显示使用噻唑烷二酮类药物的患者的骨折风险高于使用二甲双胍的患者,当前结果支持以下假设,即噻唑烷二酮类药物可降低骨密度、刺激脂肪细胞和破骨细胞分化、并抑制成骨细胞分化进而导致骨折风险增加。虽然磺酰脲类药物与骨折风险增加之间的关联为新观察到的关联,但值得进一步研究。

该研究未探讨联合药物治疗的作用。

Mehta医生声明无经济利益冲突。

随刊述评:尚不需改变临床实践

Dr. Amanda Adler

剑桥大学阿登布鲁克医院的Amanda Adler医生表示,该研究证实噻唑烷二酮类药物的骨折风险较高,并且首次观察到磺酰脲类药物与骨折风险增加相关。该研究可能存在残余混杂的问题。该研究中的混杂因素并不完全清楚。骨折发生前存在的因素可能是混杂因素,比如磺酰脲类药物使用者是否在跌倒前存在较多的低血糖值。遗憾地是,研究者未能告诉我们这点。

就噻唑烷二酮类药物而言,如果一个细胞尚未决定是成为骨细胞还是成为脂肪细胞,则在使用噻唑烷二酮类药物的情况下,该细胞将成为脂肪细胞而非骨细胞。在这种情况下,将可能存在骨细胞较少的问题。该研究试图探讨骨代谢,但未得出任何相关结果。

该研究的结果尚不足以改变临床实践。研究者可能需要回顾那些对磺酰脲类药物和其他治疗进行比较的随机研究和那些探讨骨折方面是否存在差异的荟萃分析。该研究表明其他二线药物并不明显增加骨折风险,但这些药物对骨骼的影响还有待进一步研究。

Amanda Adler医生是英国国家健康与临床优化研究所技术评估委员会的主席。

爱思唯尔版权所有未经授权请勿转载

By: SHERRY BOSCHERT, Internal Medicine News Digital Network

SAN FRANCISCO – Adults who started taking sulfonylurea drugs for diabetes were 9% more likely to develop fractures within 5 years, and patients starting thiazolidinediones were 9% more likely to have fractures, compared with patients on other medications in a retrospective study of 99,892 adults.

Those significantly increased risks emerged after adjusting for the effects of multiple factors including age, gender, region, medical conditions, and concomitant medications, Sandhya Mehta, Ph.D. and her associates reported at the annual scientific sessions of the American Diabetes Association. Patients had no prior history of fracture.

The longitudinal retrospective analysis of a large administrative claims database found a 10% incidence of fracture on sulfonylureas and 11% on thiazolidinediones, compared with 7% on biguanides (metformin), 8% on dipeptidyl peptidase-4 (DPP-4) inhibitors, 11% on meglitinide analogues, and 6% on incretin mimetic agents. After adjusting for the confounders, the hazard ratios for each of the other three types of drugs hovered around 1 and were not statistically significantly different but increased to 1.09 for sulfonylureas and 1.4 for thiazolidinediones, reported Dr. Mehta of Inovalon Inc. in Bowie, Md., a health care data analytics company.

In the cohort as a whole, 7% of patients developed fractures. Roughly 15% of patients started sulfonylureas, 3% took thiazolidinediones, 78% were on metformin, 3% took DPP-4 inhibitors, 1% were on incretinmimetics, and 1% took meglitinides.

Previous reports have shown an increased risk of fracture in patients on thiazolidinediones, compared with those on metformin, and the current results support the hypothesis that thiazolidinediones decrease bone mineral density, stimulate adipocyte and osteoclast differentiation, and inhibit osteoblast differentiation to make fracture more likely, Dr. Mehta said.

The association between sulfonylureas and increased fracture risk appears to be new, however, and deserves further study, she added.

The study did not look at the effects of combination drug therapy.

Data came from the Medical Outcomes Research for Effectiveness and Economics (MORE) Registry, which is owned by Inovalon, drawing from the years 2008-2012.

Dr. Mehta reported having no financial disclosures.

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Don’t change clinical practice yet

This study confirms that we observe more fracture risks with thiazolidinediones. To my knowledge, this is the first time that this has been shown for sulfonylureas.

One concern about the study is so-called residual confounding. The confounders were not entirely clear in the presentation. One possible confounder is what might have preceded the fracture. If, in fact, patients on sulfonylureas were having more low blood glucose values and consequently fell, then that would be interesting to know. Unfortunately, the investigators couldn’t tell us that.

With thiazolidinediones, I’ve been told that a cell that hasn’t decided yet whether it’s going to be a bone cell or a fat cell might, in the presence of a thiazolidinedione, go on to be a fat cell instead of a bone cell. In which case, you would possibly have a problem with fewer bone cells. This study set out to look at bone metabolism but, to be fair, it could not show anything about that. That was rather ambitious.

I think there is no clinical message from this as yet. The investigators might want to look back at trials that randomized people to sulfonylureas or something else and meta-analyze that to see if there were differences in fractures.

The study suggests that the other second-line agents are okay, but again, we can’t really know what they’re doing to bones without knowing if there’s something else going on. If you took a drug that made you more likely to topple over, your bones could be equally strong as those who didn’t fall over, yet you end up with a fracture.

I’m not going to change my practice on the basis of this study.

Dr. Amanda Adler is consultant physician at Cambridge University’s Addenbrooke’s Hospital and chair of the technology appraisals committee for the National Institute for Health and Clinical Excellence in England. She gave these comments in an interview at the meeting.

关键词:两种糖尿病药物;增加骨折风险


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