比較第二型糖尿病患使用不同sulfonylurea類藥物發生缺血性心臟疾病機率之研究

Comparison of different sulfonylureas in type 2 diabetes mellitus with ischemic heart disease

黃大定(Ta-Ting Huang)

指導教授 ： 楊世群

高雄醫學大學/藥學院/藥學研究所碩士在職專班/碩士(2009年)

https://doi.org/10.6832/KMU.2009.00107

摘要

研究背景】
Sulfonylurea (SU) 為目前台灣地區治療糖尿病最普遍處方的降血糖藥物之一，然而有關於 SU 增加缺血性心臟病事件發生機率之相關討論至今仍未有明確定論。
其發生原因目前推論為藥物對於 SU receptor 的選擇性；由於SU receptor 不僅存在胰島中，亦存在心肌細胞中，當 SU 藥物不具選擇性時，將將同時與刺激胰島細胞及心肌細胞的 SU receptor 結合並導致缺血性心臟病事件發生，因此也研發出市面上號稱第二代的SU，宣稱具有 SU receptor 選擇性。
本研究以91年度之全民健保資料庫為研究基礎進行分析統計，分為 old SU、new SU、non SU，觀察各組間缺血性心臟疾病發生機率。
【研究目的】
評估不同的 SU 類降血糖藥對於第二型糖尿病患發生缺血性心臟疾病之機率是否有所不同。
【研究方法】
本研究採用之資料庫為中央健康保險局以2000年承保人為主檔之系統抽樣檔，抽樣人數為20萬人，以2002年之20萬人系統抽樣檔作為篩選基礎註。
資料庫篩選方式以第二型糖尿病患【ICD 9 Code：250】做初步篩選，再以之分類將台灣所用之5種 SU 以健保局之藥品代碼篩選；缺血性心臟疾病之定義以資料庫顯示【ICD 9 Code：410~414】為篩選收錄標準
收案標準：
1.糖尿病患（無論第一型或第二型）。
2.年齡大於20歲。
排除標準：
1. 在2002年間連續使用同一降血糖藥（包含胰島素）未超過半年或於追蹤期間 (2002-2004) 轉換不同 SU 者。
2. 在糖尿病發病前已有缺血性心臟疾病史。
3. 年齡小於20歲。
以上述條件篩選出之資料分為5組：non SU、old SU、glipizide、gliclazide、glimepiride，以 non SU 作為標準組，四組 SU 對照組與標準組比較缺血性心臟疾病之發生機率。
【研究結果】
總收錄病患數為7704人，初步統計結果顯示 non SU drug 組
(n=6274) 缺血性心臟疾病發生人數為397人 (6.33％) 、old SU drug組 (n=351) 發生人數26人 (7.41%)，odds ratio 1.18 (0.78~1.79)、glipizide組 (n=300) 發生人數16人 (5.33%)，odds ratio 0.83 (0.50~1.39)、gliclazide組 (n=324) 發生人數22人 (6.79%)，odds ratio 1.08 (0.69~1.68)、glimepiride組 (n=455) 發生人數23人 (5.05%)，odds ratio 0.79 (0.51~1.21)。
由於各組間年齡、男性比例、相關之干擾缺血性心臟疾病發生之用藥比例等皆有明顯差別，經統計調整後 old SU drug 組 odds ratio 1.09 (0.72~1.66)、glipizide組 0.76 (0.45~1.28)、gliclazide組0.98
(0.62~1.53)、glimepiride組 0.80 (0.52~1.24)。
【結論】
此研究統計結果顯示以 glibenclamide為主之 old SU 組有較高之缺血性心臟疾病發生率，而其他 SU 組則相對有較低之發生率，但其差異性皆未達到統計上之意義。

註：
本研究部分資料來源為衛生署中央健康保險局提供、財團法人國家衛生研究院管理之『全民健康保險研究資料庫』。文中任何闡釋或結論不代表衛生署中央健康保險局、或財團法人國家衛生研究院之立場。

關鍵字

第二型糖尿病 ； 缺血性心臟疾病

並列摘要

Abstract
Background:
On account of efficacy and recommendation of diabetic treatment guideline, sulfonylurea (SU) has been widely used to treat type 2 diabetes in Taiwan for a long time. However, some published papers pointed out that some kinds of SU like glibenclamide (glyburide) might increase the incidence of ischemic heart disease in type 2 diabetics.
We always nominate “second generation of SU ”as which have beta-cell selectivity and can avoid increasing the incidence of ischemic heart disease. Therefore, the purpose of our study is to clarify if different kinds of SU would have different effect on heart.

Objective
To evaluate the incidence of SU related ischemic heart disease on type 2 diabetes patients

Material and Methods:
This is a retrospective study enrolling data from Taiwan Bureau of National Health Insurance from 2002 to 2004 system. The sampling data included 200000 subjects. Statistical analysis was performed using SAS statistics system and matched by age and gender. The inclusion criteria were ICD-9 Code 250 (Diabetes), aged 20-95 year-old and defining ischemic heart disease as ICD-9 Code: 401~414. The patients should continue taking the same SU more than 6 months. The exclusion criteria were patients who have had ischemic heart disease before including period, aged less than 20 year-old and changing SU category during follow-up period. Enrolled subjects were separated to five groups: non SU group, old SU group (including glibenclamide and chlorpropamide), glipizide, gliclazide and glimepiride. The non SU group was defined as the reference group to evaluate the incidence of ischemic heart disease of other four groups.

Results:
There were 7704 patients enrolled. In non SU group (n = 6274), there were 397 (6.33%) patients getting ischemic heart disease during following period. The patient’s number of suffering from ischemic heart disease during follow-up were 26 (7.41%) on old SU (n = 351), 16 (5.33%) on glipizide (n = 300), 22 (6.79%) on glicalzide (n = 324) and 23 (5.05%) on glimepiride (n = 455) superlatively. The odds ratio were old SU drug group 1.18 (0.78~1.79)、glipizide group 0.83 (0.50~1.39)、gliclazide group 1.08 (0.69~1.68)、glimepiride group 0.79 (0.51~1.21) Superlatively
The age、gender、use of blood pressure lowering drugs、lipid lowering drugs、aspirin、clopidogrel were significant difference between groups；Old SU drug group odds ratio 1.09 (0.72~1.66)、glipizide group 0.76 (0.45~1.28)、gliclazide group 0.98 (0.62~1.53)、glimepiride group 0.80 (0.52~1.24) after adjusted。
Conclusions:
Our result reveals that the patients on old SU had higher incidence of ischemic heart disease than other antidiabtic agents. Although, the incidence of ischemic heart disease was not significant in each group, the relative risk was even higher in old SU group after comparing with the other groups.
Among oral antidiabetic agents, old SU might be the last choice for type 2 diabetes patients, especially for the patients complicated with ischemic heart disease.

並列關鍵字

type 2 diabetes ； sulfonylurea ； ischemic heart disease

參考文獻

參考文獻

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