硫醯基尿素類藥物的死亡率高於Metformin


  【24drs.com】根據發表於ENDO 2012:內分泌協會第94屆年會一項超過23,000名第2型糖尿病患的分析,糖尿病藥物glipizide、glyburide和glimepiride的死亡率風險都顯著高於metformin。
  
  這三個藥物都屬於硫醯基尿素類(sulfonylureas),在最近的安全性研究顯示比原本認知的有更多差異,特別是在低血糖風險、硫醯基尿素受體選擇性、心肌缺血預適應方面。
  
  俄亥俄州Summa西儲醫院內分泌科Kevin M. Pantalone醫師表示,有關這些藥理性質差異是否造成心血管副作用和整體死亡率之差異的報告各異;這些研究結果令我們提出兩個問題:藥理性質上的這些差異是否造成整體死亡率風險的差異?而這些藥物歷來未曾被適當分析?
  
  為了找到答案,Pantalone醫師和克里夫蘭診所的研究者一起檢視了該中心電子資料庫的23,915名第2型糖尿病患;研究對象包括了12,774名第2型糖尿病患、曾接受metformin單一治療,4,325人接受glipizide,4,279人接受glyburide,2,537人接受glimepiride,平均年紀為61歲,69%是男性,部分病患有冠狀動脈疾病史。
  
  追蹤期間中位數為2.2年,整個世代共有2,546人死亡,其中419例發生在有冠狀動脈疾病的2,721人。
  
  結果顯示,相較於metformin,glipizide (風險比[HR],1.64;95%信心區間[CI],1.39 - 1.94)、glyburide (HR,1.59;95% CI,1.35 - 1.88)和glimepiride (HR,1.68;95% CI,1.37 - 2.06)的整體死亡率風險增加。
  
  同時有糖尿病和心臟病的患者中,只有glimepiride並未造成死亡風險高於metformin;不過,Glipizide與心臟病患者的死亡率風險增加41%有關,glyburide與死亡風險增加38%有關。
  
  Pantalone醫師表示,研究結果指出,glipizide、glyburide和glimepiride都與整體死亡率風險高於metformin有關,因此,若無禁忌症時,metformin應作為控制血糖的第一線用藥。
  
  如果需要用硫醯基尿素類製劑來控制第2型糖尿病患者的血糖,對於有潛在冠狀動脈疾病者,glimepiride是比較適合的藥物。
  
  他呼籲進行更多前瞻研究,以確認個別硫醯基尿素類製劑的藥理性質差異,對於心血管結果和整體死亡率風險的影響,特別是有冠狀動脈疾病者。
  
  Pantalone醫師相信這很重要,因為美國糖尿病協會建議將硫醯基尿素類製劑作為第1級核心驗證的治療,所以,如果有證據認為某一種硫醯基尿素類製劑比其他更安全或可能更安全,那麼,就比較不用擔心使用這類藥物會有潛在害處。
  
  主持該會議的內分泌科Dace L. Trence醫師表示,雖然追蹤期間僅2.2年為其研究限制,但該研究結果與諸多研究一致,顯示硫醯基尿素類製劑之間有重要差異。
  
  華盛頓大學醫學系助理教授Trence醫師表示,越來越多證據顯示,應考慮使用某一特定的硫醯基尿素類製劑;她表示,這篇最新研究的強度在於研究對象數量與取得的醫療紀錄。
  
  儘管證據增加中,對於個別硫醯基尿素類製劑之間的明顯區別並無太多警覺;她不認為藥物之間的差異對於一線照護領域有所影響。內分泌科醫師對這個議題的警覺是有提高,但她不認為「並非每個硫醯基尿素類製劑都一樣」這個議題有被廣泛認知。
  
  資料來源:http://www.24drs.com/professional/list/content.asp?x_idno=6873&x_classno=0&x_chkdelpoint=Y
  

Sulfonylureas Show Higher Mortality Rates Than Metformin

By Nancy A. Melville
Medscape Medical News

June 29, 2012 (Houston, Texas) — The diabetes drugs glipizide, glyburide, and glimepiride each show a significantly higher risk for mortality compared with metformin, according to an analysis of more than 23,000 patients with type 2 diabetes presented here at ENDO 2012: The Endocrine Society 94th Annual Meeting.

The 3 drugs are all sulfonylureas, which have been shown in recent research to have safety profiles that are more varied between drugs than was previously believed, particularly in terms of issues such as hypoglycemic risks, sulfonylurea receptor selectivity, and the drugs' effects on myocardial ischemic preconditioning.

"There have been conflicting reports on whether these differences in pharmacological properties actually translate to differences in the risk of adverse cardiovascular outcomes and overall mortality," said lead author Kevin M. Pantalone, DO, an endocrinologist at Summa Western Reserve Hospital in Cuyahoga Falls, Ohio.

"These findings led us to ask 2 questions: Do these differences in pharmacological properties translate to differences in risk of overall mortality, and has it been inappropriate to analyze these medications as a class, as has historically been the case?"

In an effort to find the answers, Dr. Pantalone teamed up with researchers at the Cleveland Clinic in Ohio to identify 23,915 patients with type 2 diabetes in the center's electronic health record database. The study received funding from a grant from Astra Zeneca.

The participants included 12,774 patients with type 2 diabetes who had received monotherapy with metformin, 4325 patients receiving glipizide, 4279 patients receiving glyburide, and 2537 patients receiving glimepiride. Average age was 61 years, 69% were men, and the patients were both with and without a history of coronary artery disease.

At a median follow-up of 2.2 years, there were a total of 2546 deaths in the entire cohort, as well as 419 deaths among the subgroup of 2721 patients with coronary artery disease.

The results showed that compared with metformin, the overall mortality risk was increased with glipizide (hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.39 - 1.94), glyburide (HR, 1.59; 95% CI, 1.35 - 1.88), and glimepiride (HR, 1.68; 95% CI, 1.37 - 2.06).

Among patients with both diabetes and heart disease, only glimepiride did not increase the risk for death compared with metformin. Glipizide, however, was associated with a 41% increased risk for mortality among the patients with heart disease, and glyburide was associated with a 38% greater risk for death.

"The findings indicate that glipizide, glyburide, and glimepiride are all associated with an increased risk of overall mortality compared with metformin. Therefore, metformin, when not contraindicated, should be the first-line agent to prescribe to control glycemia," Dr. Pantalone said.

"If a sulfonylurea is required to obtain glycemic control in patients with type 2 diabetes, then glimepiride may be the preferred drug in those with underlying coronary artery disease."

He called for more prospective studies to determine the difference in pharmacologic properties inherent to individual sulfonylureas regarding the risk for adverse cardiovascular outcomes and overall mortality, particularly in patients with coronary artery disease.

"I believe this is very important because the American Diabetes Association recommends sulfonylureas as a tier 1, core validated therapy," Dr. Pantalone said.

"So if there is evidence that 1 sulfonylurea may be safer or potentially safer than others, then it would not make sense to use those agents that are potentially deleterious."

Although noting that the average follow-up period of just 2.2 years was a limitation of the study, endocrinologist Dace L. Trence, MD, who moderated the session, said the study's findings are in line with growing research showing important differences between sulfonylureas.

"The evidence continues to mount that there should be a consideration of the specific sulfonylurea that is used," said Dr. Trence, who is an assistant professor with the University of Washington's Department of Medicine in Seattle.

"The strength of this latest study is the number of individuals and medical records the researchers were able to access," she told Medscape Medical News.

Despite the growing evidence, there is not much awareness of the apparent distinctions between individual sulfonylurea drugs, she added.

"I don't think the differences between drugs in are appreciated in the primary care arena. I think endocrinologists are increasingly becoming aware of this issue, but I don't think it's widely known that not all sulfonylureas are created equal."

The study received funding from a grant from Astra Zeneca, and Dr. Pantalone disclosed that he has been a speaker on behalf of AstraZeneca. Dr. Trence has disclosed no relevant financial relationships.

ENDO 2012: The Endocrine Society 94th Annual Meeting: Abstract OR17-4. Presented June 24, 2012.

    
相關報導
單靠篩檢與治療無法預防第二型糖尿病
2017/1/12 上午 11:07:07
Metformin緩解自閉症患者使用抗精神病藥後的體重增加情況
2016/9/7 下午 03:03:24
Metformin失敗之後 延遲強化治療常見
2016/8/31 下午 01:57:15

上一頁
   1   2   3   4   5   6   7   8   9   10  




回上一頁