第二型糖尿病使用DPP-4抑制劑藥物與急性胰臟炎發生之相關連結性研究

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Title:	第二型糖尿病使用DPP-4抑制劑藥物與急性胰臟炎發生之相關連結性研究 Investigation the possible connection between dipeptidyl-peptidase (DPP)-4 inhibitors and the development of acute pancreatitis in type II diabetic patients
Authors:	吳士慧
Contributors:	藥學系施美份
Keywords:	第二型糖尿病急性胰臟炎 DPP-4抑制劑多重藥物治療藥物不良反應 Type 2 diabetes Acute pancreatitis DPP-4 inhibitors Multiple drug therapy Adverse drug reactions
Date:	2017
Issue Date:	2018-01-11 11:44:30 (UTC+8)
Abstract:	現今第二型糖尿病發生率上升，研究顯示預估糖尿病人口至2025年止人數將由1.35億上升至3億。近年來新作用機轉之降血糖藥物之開發陸續推出，其中一類藥物為DPP-4I (Dipeptidyl-peptidase (DPP)-4 inhibitors，DPP-4I)。由於DPP-4I 本身不會引起低血糖風險，且為口服因此使用DPP-4I人數逐年升高。第二型糖尿病急性胰臟炎發生機率目前研究約為12.8％，高於一般族群10.5％，其發生原因除高血脂症、酒精過量、及膽結石外，藥物亦為其中之一。雖然國內、外已發表許多有關DPP-4I引發急性胰臟炎不良反應 (Adverse drug reactions/ADRs )之案例，但這研究尚未在台中某教學醫院進行過，因此想藉由此院資料庫探討這兩者之間關係，推測加入此類藥物上升急性胰臟炎發生機率，藉此提升對此副作用的警示，以增加病人使用此類藥物之安全性。本研究收集樣本資料來源取至中部某教學醫院院內臨床資料庫，時間由2010年1月1日至2016年10月31日止。以診斷碼 (ICD-9,10 code)擷取第二型糖尿病患樣本數，搜尋其中急性胰臟炎案例，並以藥理治療分類碼與國際分類碼 (AHFS) 搜尋第二型糖尿病患可能引起急性胰臟炎及其他相關藥物。符合篩選條件之人數中共有3971人，依急性胰臟炎 (acute pancreatitis，AP) 區別，沒有發生AP的案例較有發生者明顯較多，但可見性別、年齡、共病症 (包括膽結石、有抽菸)、用藥部分間 (PPIs、NSAIDs) 有明顯關聯性 (p < 0.0001)。單一降血糖藥物之間急性胰臟炎發生比率彼此之間並無差異 (DPP-4I : 8.57%、Sulfonylurea : 8.05%、Others : 9.94%)。兩種降血糖藥物合併使用則發現DPP-4I並用Sulfonylurea 誘發AP的比率明顯上升至15.79%，但三種降血糖藥物併用發生AP的比率為 7.14%；就多種降血糖藥物再合併其他已知易促進AP發生的藥物，如NSAIDs、ACEI、PPIs等，結果發現AP的發生機率大幅提高至50%以上。DPP-4I本身對於AP的發生機率在此研究中並無明顯增加的現象，但是併用sulfonylurea可能會大幅提高發生AP的發生機率。此外病患本身年齡、性別及有、無相關共病症可能也是導致再使用這些藥物時引起AP的原因之一。降血糖及非降血糖藥物的多重藥物併用下導致AP發生機率相對增加，這個發現需要再深入研究，若是屬實則須提出警示以免更多醫師在不知情形之下開立這些藥物導致病患發生AP的併發症。 The incidence of type 2 diabetes increased and the study showed that the population of diabetes in 2025 will be increased from 135 million to 300 million. Recently, the new class of DPP-4I (Dipeptidyl-peptidase (DPP)-4 inhibitors) can be used in the treatment of type 2 diabetes. Due to low risk of hypoglycemia and easy to use, lead to increased number of people using DPP-4I. The prevalence of diabetes for the worldwide was estimated to 12.8% and higher than the general population 10.5%. The most common etiology for acute pancreatitis is caused by hyperlipidemia, alcohol abuse and gallstones. Other causes are usually due to medications. Although there have been many adverse reactions (ADRs) cases of DPP-4I-induced acute pancreatitis (AP) from Chinese and abroad. This study has not yet been conducted in a teaching hospital in Taichung, so would like to use this library to discuss the relationship between the two. This retrospective study was carried out at Academic Medical Centers (Taichung city). Between January 1, 2010 and October 31, 2016, a total of 3971 by collecting prescriptions of type 2 diabetes and search for AP cases (ICD-9, 10 codes). Initial analysis of total of 3971 patients according to the AP and non-AP have significant differences in sex, age, common disease (including gallstones, smoking) and some medications (PPIs, NSAIDs) (p <0.0001). There was no difference in the incidence of AP between single hypoglycemic agents (DPP-4I: 8.57%, Sulfonylurea: 8.05%, 9.94%). The combination of two hypoglycemic agents about DPP-4I plus Sulfonylurea induced AP significantly increased to 15.79%, but the three hypoglycemic agents induced the occurrence of AP with a lower rate of 7.14%. Multiple medications of hypoglycemic drugs and other known to promote AP drugs, such as NSAIDs, ACEIs, PPIs, etc., the results found that AP probability of a substantial increase to more than 50%. DPP-4I has no significant increases the incidence of AP in this study, but combined with sulfonylurea may significantly increase the incidence. In addition, the patient's own age, sex, and comorbidities may also be one of the reason of AP when AP is occurs again. Multidrug treatment of type 2 diabetes about hypoglycemic combine with non-hypoglycemic drugs can induces the occurrence of AP. The findings need to further study and make a warning to clinicians.
Relation:	電子全文公開日期：2022-08-08，學年度：105，96頁
Appears in Collections:	[Dept. of Pharmacy] Dissertations and Theses

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