臺灣博碩士論文加值系統

研究背景：糖尿病和癌症均名列為國人前十大死因，皆屬國人之重要健康議題，近年來有越來越多研究顯示，第2型糖尿病病患有較高的癌症風險（包括罹病率和相關死亡率），而降血糖藥物為第2型糖尿病之主要治療方式，過去也有文獻指出降血糖藥物與癌症間的相關性，故本研究目的為利用台灣健康保險資料庫以第2型糖尿病病患為研究族群探討降血糖藥物與癌症間的相關性。

研究方法：本研究採重疊病例對照研究 (Nested case-control study)，使用資料為國衛院健康保險資料庫2005年百萬人承保抽樣歸人檔，篩選1997-1999年30歲以上第2型糖尿病病患為研究族群，病例組為研究族群於研究期間內（1997-2007）首次出現癌症診斷記錄者，對照組則由配對病例組而得，回溯兩組個案於指標日前之過去用藥記錄，再進行兩組間不同降血糖藥物之分析。

研究結果：研究族群共16,450人，總追蹤年數為160,808人年，病例組有2,687人，非病例組經1：2配對年齡、性別、指標年份、追蹤年數（±1年）等可能影響癌症風險之因子後得對照組5,369人。經過調整共病症和其他並用之降血糖藥物後，暴露於兩類降血糖藥物的病患有顯著性較高的癌症風險（調整後勝算比為1.16，95%信賴區間為1.03到1.31）；且其中以合併暴露於Metformin和Sulfonylureas雙藥物治療有顯著性較高的癌症風險（調整後勝算比為1.13，95%信賴區間為1.02到1.25）；另外，有暴露於Sulfonylureas，雖然未達顯著，但有較高之癌症風險趨勢（調整後勝算比為1.11，95%信賴區間為1.00到1.25）；而Sulfonylureas 中以Glyburide（Glibenclamide）有顯著性較高的癌症風險（調整後勝算比為1.15，95%信賴區間為1.01到1.31）。其他降血糖藥物治療包括：Meglitinides、Insulin、Thiazolidinediones（TZD）和Acarbose與癌症風險則未有顯著相關性。

結論：降血糖藥物中，Sulfonylureas有較高癌症風險的趨勢，其中又以Glyburide（Glibenclamide）有顯著性較高之癌症風險，而合併Sulfonylureas和Metformin也有顯著性較高之癌症風險，其他降血糖藥物則未發現與癌症風險有顯著相關性。

Background: Several studies have suggested an association between specific antidiabetic medications and cancer morbidity. This study was aimed at the assessment of association between different antidiabetic medications and cancer risks by using Taiwan National Health Insurance claims database.

Methods: We used the Longitudinal Health Insurance Database 2005 (LHID 2005) (1997-2007) to conduct a nested matched case-control study. Among the study population of type 2 diabetic patients, we identified 2,687 ptaients who had an incident malignancy. 5,369 controls were matched with the corresponding cases for age, sex, duration of follow-up and index year. Multiple logistic regression was used and ORs were estimated for assessing association between antidiabetic medications and cancer risks.

Results: Dual therapy of metformin and Sulfonylureas was significant associated with higher cancer risks (adjusted OR 1.13, 95%CI 1.02-1.25). Among Sulfonylureas, glyburide (glibenclamide) treatment was associated with a significant higher cancer risks (adjusted OR 1.15, 95%CI 1.01-1.31). There was no significant association between treatment with meglitinides, insulin, thiazolidinediones, or acarbose and cancer risk. And long-term treatments also showed no significant association with cancer risk.

Conclusion: The results of this study show that only Sulfonylureas has a trend to increase cancer risks whereas other antidiabetic medications do not. Dual therapy with metformin and Sulfonylureas shows significant higher cancer risk. And the duration of antidiabetic medication exposure didn’t show well association with cancer risks. Further studies are needed to confirm the results.

中文摘要 I
ABSTRACT III
表目錄 IX
圖目錄 XI
附錄目錄 XII
第壹章 緒論 1
第貳章 文獻探討 2
第一節 糖尿病流行病學簡介 2
第二節 糖尿病簡介 3
第三節 降血糖藥物簡介 4
一、 Metformin 5
二、 Sulfonylureas 5
三、 Meglitinides 5
四、 Thiazolidinediones（TZD） 6
五、 α-Glucosidase inhibitors 6
六、 Insulin（胰島素） 6
七、 Dipeptidyl peptidase four inhibitor（DPP4I） 7
第四節 糖尿病與癌症 8
第五節 糖尿病類型與癌症 9
第六節 其他影響因子 10
第七節 降血糖藥物與癌症 10
第參章 研究目的與目標 13
第一節 研究動機與目的 13
第二節 研究目標 13
一、 評估不同降血糖藥物與癌症風險相關性 13
二、 評估不同類別降血糖藥物間之各藥物品項與癌症風險相關性 13
三、 評估各類降血糖藥物累積暴露天數與癌症風險相關性 14
第肆章 研究方法 15
第一節 研究對象與資料來源 15
第二節 研究假設 15
第三節 人群基礎病例對照研究 16
一、 研究架構 16
二、 研究族群定義 17
三、 研究變項說明與定義 17
四、 資料處理流程 20
第四節 重疊病例對照研究 26
一、 研究架構 26
二、 研究族群定義 26
三、 研究變項說明與定義 27
四、 資料處理流程 31
第五節 統計分析 37
一、 描述性統計分析 37
二、 推論性統計分析 37
第六節 統計分析工具 37
第伍章 研究結果 38
第一節 人群基礎病例對照研究 38
一、 基本資料描述 38
二、 用藥分析 41
第二節 重疊病例對照研究 51
一、 基本資料描述 51
二、 用藥分析 55
第陸章 討論 66
第一節 研究設計之比較 66
第二節 第2型糖尿病之癌症發生率 68
第三節 降血糖藥物與癌症風險之相關性 68
一、 降血糖藥物暴露總種類數 68
二、 Metformin和Sulfonylureas 68
三、 同類降血糖藥品之不同品項 70
四、 其他降血糖藥物 71
第四節 降血糖藥物累積暴露時間與癌症風險的相關性 71
第五節 分析變項討論 72
第六節 癌症其他相關風險因子 73
第七節 優點與限制 74
第八節 建議未來研究方向 75
第柒章 結論 76
第捌章 參考文獻 77
附錄 83

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