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系統識別號 U0026-1808202013261500
論文名稱(中文) 台灣第二型糖尿病合併嚴重腎功能不全患者DPP-4 inhibitors之真實世界使用情況、臨床效益與安全性
論文名稱(英文) Real-world use, effectiveness, and safety of dipeptidyl peptidase-4 inhibitors in a Taiwanese population with type 2 diabetes and advanced chronic kidney disease
校院名稱 成功大學
系所名稱(中) 臨床藥學與藥物科技研究所
系所名稱(英) Institute of Clinical Pharmacy and Pharmaceutical sciences
學年度 108
學期 2
出版年 109
研究生(中文) 李侖桀
研究生(英文) Lun-Jie Li
學號 S66074039
學位類別 碩士
語文別 中文
論文頁數 154頁
口試委員 指導教授-歐凰姿
共同指導教授-林威宏
共同指導教授-吳玉琴
口試委員-吳宗軒
口試委員-賴嘉鎮
中文關鍵字 第二型糖尿病  嚴重腎功能不全  DPP-4 inhibitors  進展至長期透析或腎臟移植 
英文關鍵字 type 2 diabetes  advanced chronic kidney disease  dipeptidyl peptidase-4 inhibitors  chronic dialysis or kidney transplant 
學科別分類
中文摘要 研究背景與目的
根據統計,目前全世界約有20-40%的第二型糖尿病患者合併有慢性腎臟病,且在台灣的數據有逐年上升的趨勢,伴隨的相關併發症風險與醫療負擔隨之增加。針對嚴重腎功能不全患者的重要議題之一即為延緩進展至長期透析或腎臟移植,而面對愈來愈多證據顯示特定降血糖藥品可能存在腎臟保護效果,例如dipeptidyl peptidase 4 inhibitors (DPP4i),加上對於第二型糖尿病合併嚴重腎功能不全患者的降血糖藥品治療相對有限,在考量安全性與使用方便性上,DPP4i可能會是比較好的治療選擇。儘管如此,目前針對這類族群的腎臟相關風險研究仍然缺乏,因此需要進一步研究做為臨床決策的依據。
首先,我們想要了解台灣第二型糖尿病患者被確認有嚴重腎功能不全之後的降血糖藥品處方型態;再者,我們想要分析DPP4i與另一個常用的第二線降血糖藥品sulfonylureas (SU) 於這群病患的相對療效與安全性,而我們觀察到DPP4i與SU有同時處方的情形,因此另外分析DPP4i + SU與SU。

研究方法
本研究利用2007-2016年台灣全民健康保險資料庫,篩選出2008-2015年新診斷第二型糖尿病的成年患者,其後於2011-2015年藉由台灣末期腎臟病前期之病人照護與衛教計畫 (pre-ESRD program) 確認為嚴重腎功能不全患者。針對以上符合條件的病患,再篩選出進入pre-ESRD program後有使用任何降血糖藥品的病患做為處方型態分析;進入pre-ESRD program後有穩定使用DPP4i或SU,並且排除先前有長期透析、腎臟移植或是接受過紅血球生成刺激劑的病患做為相對療效與安全性分析,這裡採用prevalent user design與two-step matching algorithm來做為研究族群的篩選與配對標準。
研究結果包含進展至長期透析或腎臟移植、因為心衰竭而入院、心血管疾病事件 (包含因為心肌梗塞、中風而入院,與心因性死亡)、加入考量因為心衰竭而入院的心血管疾病事件、因為低血糖而入院與全死因死亡,以上相關風險計算主要以subdistribution hazard model來呈現DPP4i相較於SU,或是DPP4i + SU相較於SU的事件發生風險。

研究結果
在處方型態分析觀察到病患進入pre-ESRD program之後,DPP4i的使用比例上升幅度最大 (18.1%),且在一年後的使用比例為各個降血糖藥品中最高者 (45.7%)。在相對療效與安全性分析觀察到,DPP4i相較於SU能顯著降低45%因為低血糖而入院之風險,其他結果如進展至長期透析或腎臟移植、心血管疾病事件並沒有觀察到兩者有顯著差異。不過,對於因為心衰竭而入院則發現DPP4i相較於SU會顯著提升24%風險,其中saxagliptin與vildagliptin更是會分別提升69%與64%的風險;至於DPP4i + SU相較於SU於整體來說,並沒有觀察到兩者有顯著差異,除了DPP4i + SU能顯著下降33%進展至長期透析或腎臟移植之風險,然而研究樣本數相對較小,仍需進一步研究來佐證。

研究結論
對於台灣第二型糖尿病合併嚴重腎功能不全患者,DPP4i的使用有上升趨勢,而DPP4i相較於SU而言有較低的低血糖風險,同時有相似的腎臟、心血管安全性,然而saxagliptin與vildagliptin可能有較高的心衰竭風險,建議針對有相關疑慮的患者採用較為安全的linagliptin與sitagliptin。
英文摘要 SUMMARY
We aimed to analyze the prescription patterns of glucose-lowering agents (GLAs) among type 2 diabetes (T2D) patients with advanced chronic kidney disease (CKD) in Taiwan, and to further assess the effectiveness and safety outcomes, in terms of CKD progression, cardiovascular diseases, mortality, and hospitalized hypoglycemia associated with dipeptidyl peptidase-4 inhibitors (DPP4i) versus sulfonylureas (SU) to inform the clinical decisions. The population-based cohort study was conducted using Taiwan’s National Health Insurance Research Database 2007-2016. The prevalent user design and two-step matching algorithm were adopted in the study. Competing risks of death were considered in the subdistribution hazard models. The results showed that DPP4i and SU were the two most frequently used GLAs among T2D patients with confirmed status of advanced CKD. The use of DPP4i compared with SU among this population was associated with a lower risk of hospitalized hypoglycemia and comparable safety profiles of renal and cardiovascular outcomes. Moreover, saxagliptin and vildagliptin were associated with a potential risk of hospitalized heart failure, but linagliptin and sitagliptin were not and thus could be the preferred treatment options given a concern of heart failure.

論文目次 中文摘要 I
Extended abstract III
誌謝 VII
表目錄 XIII
圖目錄 XV
第一篇 台灣第二型糖尿病合併嚴重腎功能不全患者DPP-4 inhibitors之真實世界使用情況、臨床效益與安全性 1
第一章 研究背景 1
第二章 文獻回顧 2
第一節 第二型糖尿病合併慢性腎臟病 2
2.1.1 第二型糖尿病之定義與診斷 2
2.1.2 第二型糖尿病之血管併發症 3
2.1.3 慢性腎臟病之定義與分期 4
2.1.4 第二型糖尿病合併慢性腎臟病之盛行率與醫療負擔 5
2.1.5 第二型糖尿病合併慢性腎臟病之致病機轉與臨床症狀 6
2.1.6 第二型糖尿病合併慢性腎臟病之相關疾病風險 7
第二節 第二型糖尿病合併嚴重腎功能不全患者之降血糖治療 8
2.2.1 第二型糖尿病之降血糖治療指引 8
2.2.2 第二型糖尿病合併嚴重腎功能不全患者之降血糖治療選擇 10
第三節 DPP-4 inhibitors 12
2.3.1 簡介DPP-4 inhibitors與其器官保護機轉 12
2.3.2 DPP-4 inhibitors之目前研究證據 15
第三章 研究目的 26
第一節 研究動機 26
第二節 研究目的 27
第三節 研究假說 27
第四章 研究方法 28
第一節 研究設計 28
4.1.1 研究類型 28
4.1.2 研究材料 28
4.1.3 研究對象 29
4.1.4 研究對象配對流程 31
4.1.5 研究藥品 34
4.1.6 觀察結果 34
4.1.7 研究流程與觀察區間 35
4.1.8 研究變數 37
4.1.9 人體試驗委員會核備 37
第二節 研究名詞與操作型定義 38
第三節 統計分析 47
第五章 研究結果 50
第一節 研究對象之篩選流程結果 50
第二節 降血糖藥品處方型態分析 52
第三節 研究對象之基本特徵:DPP-4 inhibitors versus sulfonylureas 55
5.3.1 未經配對之基本特徵 55
5.3.2 配對後之基本特徵 56
第四節 研究藥品之臨床療效與安全性分析:DPP-4 inhibitors versus sulfonylureas 63
5.4.1 主要分析 (primary analyses) 63
5.4.2 次族群分析 (subgroup analyses) 67
5.4.3 敏感度分析 (sensitivity analyses) 70
第五節 研究對象之基本特徵:DPP-4 inhibitors + sulfonylureas versus sulfonylureas 75
5.5.1 未經配對之基本特徵 75
5.5.2 配對後之基本特徵 76
第六節 研究藥品之臨床療效與安全性分析:DPP-4 inhibitors + sulfonylureas versus sulfonylureas 83
5.6.1 主要分析 (primary analyses) 83
5.6.2 次族群分析 (subgroup analyses) 87
5.6.3 敏感度分析 (sensitivity analyses) 89
第六章 研究討論 93
第一節 降血糖藥品處方型態分析之討論 93
第二節 研究族群基本特徵之討論 95
第三節 DPP-4 inhibitors versus sulfonylureas之討論 96
第四節 DPP-4 inhibitors + sulfonylureas versus sulfonylureas之討論 105
第七章 研究優勢與限制 107
第一節 研究優勢 107
第二節 研究限制 108
第八章 結論及建議 109
第九章 未來研究方向 110
第二篇 臨床藥事服務 111
第一章 服務緣起 111
第二章 臨床藥師病房照護 111
第一節 服務內容 111
第二節 服務成果 112
第三節 討論與建議 116
第三章 其他臨床藥事服務─糖尿病衛教手冊 117
第一節 服務內容 117
第二節 服務成果 117
第四章 未來建議與感想回饋 124
參考資料 125
附錄 131
參考文獻 1. World Health Organization. Diabetes. https://www.who.int/news-room/fact-sheets/detail/diabetes. Accessed June 15, 2020.
2. Meda E. Pavkov, et al: Kidney Disease in Diabetes. Chapter 22 in Diabetes in America, 3rd ed. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, NIH Pub No. 17-1468, 2018, p. 22.1–22.84.
3. United States Renal Data System. 2018 USRDS annual data report: Epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2018.
4. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020;43(Suppl 1):S98-s110.
5. Buse JB, Wexler DJ, Tsapas A, et al. 2019 Update to: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2020;43(2):487-493.
6. White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013;369(14):1327-1335.
7. Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369(14):1317-1326.
8. Green JB, Bethel MA, Armstrong PW, et al. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2015;373(3):232-242.
9. Rosenstock J, Perkovic V, Johansen OE, et al. Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk: The CARMELINA Randomized Clinical Trial. Jama. 2019;321(1):69-79.
10. Rosenstock J, Kahn SE, Johansen OE, et al. Effect of Linagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes: The CAROLINA Randomized Clinical Trial. Jama. 2019;322(12):1155-1166.
11. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020;43(Suppl 1):S14-s31.
12. Paneni F, Beckman JA, Creager MA, Cosentino F. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I. Eur Heart J. 2013;34(31):2436-2443.
13. Deshpande AD, Harris-Hayes M, Schootman M. Epidemiology of diabetes and diabetes-related complications. Phys Ther. 2008;88(11):1254-1264.
14. 社團法人中華民國糖尿病衛教學會. 臺灣糖尿病年鑑─2019第2型糖尿病. 2019.
15. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney inter, Suppl. 2013;3:1–150.
16. 財團法人國家衛生研究院. 2015臺灣慢性腎臟病臨床診療指引. 2015.
17. Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition. Diabetes Res Clin Pract. 2019;157:107843.
18. Jiang YD, Chang CH, Tai TY, Chen JF, Chuang LM. Incidence and prevalence rates of diabetes mellitus in Taiwan: analysis of the 2000-2009 Nationwide Health Insurance database. J Formos Med Assoc. 2012;111(11):599-604.
19. 11. Microvascular Complications and Foot Care: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020;43(Suppl 1):S135-s151.
20. Huang YY, Lin KD, Jiang YD, et al. Diabetes-related kidney, eye, and foot disease in Taiwan: an analysis of the nationwide data for 2000-2009. J Formos Med Assoc. 2012;111(11):637-644.
21. Alicic RZ, Rooney MT, Tuttle KR. Diabetic Kidney Disease: Challenges, Progress, and Possibilities. Clin J Am Soc Nephrol. 2017;12(12):2032-2045.
22. Rosenson RS, Fioretto P, Dodson PM. Does microvascular disease predict macrovascular events in type 2 diabetes? Atherosclerosis. 2011;218(1):13-18.
23. House AA, Wanner C, Sarnak MJ, et al. Heart failure in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2019;95(6):1304-1317.
24. Moen MF, Zhan M, Hsu VD, et al. Frequency of hypoglycemia and its significance in chronic kidney disease. Clin J Am Soc Nephrol. 2009;4(6):1121-1127.
25. Runesson B, Xu Y, Qureshi AR, et al. Association between reduced kidney function and incident hypoglycaemia in people with diabetes: The Stockholm Creatinine Measurements (SCREAM) project. Diabetes Obes Metab. 2020;22(8):1425-1435.
26. 社團法人中華民國糖尿病學會. 2019台灣糖尿病腎臟疾病臨床照護指引. 2019.
27. Afkarian M, Sachs MC, Kestenbaum B, et al. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol. 2013;24(2):302-308.
28. Fox CS, Matsushita K, Woodward M, et al. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis. Lancet. 2012;380(9854):1662-1673.
29. Zelniker TA, Wiviott SD, Raz I, et al. Comparison of the Effects of Glucagon-Like Peptide Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus. Circulation. 2019;139(17):2022-2031.
30. Giugliano D, De Nicola L, Maiorino MI, Bellastella G, Esposito K. Type 2 diabetes and the kidney: Insights from cardiovascular outcome trials. Diabetes Obes Metab. 2019;21(8):1790-1800.
31. Garber AJ, Handelsman Y, Grunberger G, et al. CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM - 2020 EXECUTIVE SUMMARY. Endocr Pract. 2020;26(1):107-139.
32. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com. Accessed June 22, 2020.
33. Baetta R, Corsini A. Pharmacology of dipeptidyl peptidase-4 inhibitors: similarities and differences. Drugs. 2011;71(11):1441-1467.
34. Avogaro A, Fadini GP. The Effects of Dipeptidyl Peptidase-4 Inhibition on Microvascular Diabetes Complications. Diabetes Care. 2014;37(10):2884-2894.
35. Scheen AJ, Delanaye P. Renal outcomes with dipeptidyl peptidase-4 inhibitors. Diabetes Metab. 2018;44(2):101-111.
36. Muskiet MHA, Tonneijck L, Smits MM, et al. GLP-1 and the kidney: from physiology to pharmacology and outcomes in diabetes. Nat Rev Nephrol. 2017;13(10):605-628.
37. Zannad F, Cannon CP, Cushman WC, et al. Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial. Lancet. 2015;385(9982):2067-2076.
38. Cornel JH, Bakris GL, Stevens SR, et al. Effect of Sitagliptin on Kidney Function and Respective Cardiovascular Outcomes in Type 2 Diabetes: Outcomes From TECOS. Diabetes Care. 2016;39(12):2304-2310.
39. Arjona Ferreira JC, Marre M, Barzilai N, et al. Efficacy and safety of sitagliptin versus glipizide in patients with type 2 diabetes and moderate-to-severe chronic renal insufficiency. Diabetes Care. 2013;36(5):1067-1073.
40. Kim KJ, Choi J, Lee J, et al. Dipeptidyl peptidase-4 inhibitor compared with sulfonylurea in combination with metformin: cardiovascular and renal outcomes in a propensity-matched cohort study. Cardiovasc Diabetol. 2019;18(1):28.
41. Kolaczynski WM, Hankins M, Ong SH, Richter H, Clemens A, Toussi M. Microvascular Outcomes in Patients with Type 2 Diabetes Treated with Vildagliptin vs. Sulfonylurea: A Retrospective Study Using German Electronic Medical Records. Diabetes Ther. 2016;7(3):483-496.
42. Huang TL, Hsiao FY, Chiang CK, Shen LJ, Huang CF. Risk of cardiovascular events associated with dipeptidyl peptidase-4 inhibitors in patients with diabetes with and without chronic kidney disease: A nationwide cohort study. PLoS One. 2019;14(5):e0215248.
43. Liang CY, Chen DY, Mao CT, et al. Cardiovascular risk of sitagliptin in ischemic stroke patients with type 2 diabetes and chronic kidney disease: A nationwide cohort study. Medicine (Baltimore). 2018;97(52):e13844.
44. Chen DY, Wang SH, Mao CT, et al. Sitagliptin and cardiovascular outcomes in diabetic patients with chronic kidney disease and acute myocardial infarction: A nationwide cohort study. Int J Cardiol. 2015;181:200-206.
45. Chan SY, Ou SM, Chen YT, Shih CJ. Effects of DPP-4 inhibitors on cardiovascular outcomes in patients with type 2 diabetes and end-stage renal disease. Int J Cardiol. 2016;218:170-175.
46. Hung YC, Lin CC, Huang WL, Chang MP, Chen CC. Sitagliptin and risk of heart failure hospitalization in patients with type 2 diabetes on dialysis: A population-based cohort study. Sci Rep. 2016;6:30499.
47. Cheng PC, Hsu SR, Kuo JF, Cheng YC, Liu YH, Tu ST. Comparing the Effect of Dipeptidyl-Peptidase 4 Inhibitors and Sulfonylureas on Albuminuria in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A Prospective Open-Label Study. J Clin Med. 2019;8(10):1715.
48. Goldshtein I, Karasik A, Melzer-Cohen C, et al. Urinary albumin excretion with sitagliptin compared to sulfonylurea as add on to metformin in type 2 diabetes patients with albuminuria: A real-world evidence study. J Diabetes Complications. 2016;30(7):1354-1359.
49. Chu WM, Ho HE, Huang KH, et al. The prescribing trend of oral antidiabetic agents for type 2 diabetes in Taiwan: An 8-year population-based study. Medicine (Baltimore). 2017;96(43):e8257.
50. Montvida O, Shaw J, Atherton JJ, Stringer F, Paul SK. Long-term Trends in Antidiabetes Drug Usage in the U.S.: Real-world Evidence in Patients Newly Diagnosed With Type 2 Diabetes. Diabetes Care. 2018;41(1):69-78.
51. Suissa S, Moodie EE, Dell'Aniello S. Prevalent new-user cohort designs for comparative drug effect studies by time-conditional propensity scores. Pharmacoepidemiol Drug Saf. 2017;26(4):459-468.
52. 衛生福利部中央健保署. 末期腎臟病前期之病人照護與衛教計畫. https://www.nhi.gov.tw/Content_List.aspx?n=D037A6FEDF678C70&topn=5FE8C9FEAE863B46. Accessed June 15, 2020.
53. D'Agostino RB. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998;17(19):2265-2281.
54. Chang HY, Weiner JP, Richards TM, Bleich SN, Segal JB. Validating the adapted Diabetes Complications Severity Index in claims data. Am J Manag Care. 2012;18(11):721-726.
55. 李寬穎. 比較第二型糖尿病患者使用中效人類胰島素和長效胰島素類似物之臨床效益. 國立成功大學臨床藥學與藥物科技研究所碩士學位論文. 2019:1-116.
56. 張凱程. 利用台灣健保資料庫分析DPP-4 inhibitors對於第二型糖尿病病患的大血管病變的療效分析. 國立成功大學臨床藥學與藥物科技研究所碩士學位論文. 2015:1-189.
57. Economic Costs of Diabetes in the U.S. in 2017. Diabetes Care. 2018;41(5):917-928.
58. Meduru P, Helmer D, Rajan M, Tseng CL, Pogach L, Sambamoorthi U. Chronic illness with complexity: implications for performance measurement of optimal glycemic control. J Gen Intern Med. 2007;22 Suppl 3(Suppl 3):408-418.
59. Cheng CL, Lee CH, Chen PS, Li YH, Lin SJ, Yang YH. Validation of acute myocardial infarction cases in the national health insurance research database in taiwan. J Epidemiol. 2014;24(6):500-507.
60. Shao SC, Chang KC, Hung MJ, et al. Comparative risk evaluation for cardiovascular events associated with dapagliflozin vs. empagliflozin in real-world type 2 diabetes patients: a multi-institutional cohort study. Cardiovasc Diabetol. 2019;18(1):120.
61. Cheng C-L, Kao Y-HY, Lin S-J, Lee C-H, Lai ML. Validation of the national health insurance research database with ischemic stroke cases in Taiwan. Pharmacoepidemiology and Drug Safety. 2011;20(3):236-242.
62. Hsieh CY, Chen CH, Li CY, Lai ML. Validating the diagnosis of acute ischemic stroke in a National Health Insurance claims database. J Formos Med Assoc. 2015;114(3):254-259.
63. Ginde AA, Blanc PG, Lieberman RM, Camargo CA, Jr. Validation of ICD-9-CM coding algorithm for improved identification of hypoglycemia visits. BMC Endocr Disord. 2008;8:4.
64. Ikeda Y, Kubo T, Oda E, Abe M, Tokita S. Incidence rate and patient characteristics of severe hypoglycemia in treated type 2 diabetes mellitus patients in Japan: Retrospective Diagnosis Procedure Combination database analysis. J Diabetes Investig. 2018;9(4):925-936.
65. Karter AJ, Warton EM, Moffet HH, et al. Revalidation of the Hypoglycemia Risk Stratification Tool Using ICD-10 Codes. Diabetes Care. 2019;42(4):e58-e59.
66. Lau B, Cole SR, Gange SJ. Competing risk regression models for epidemiologic data. Am J Epidemiol. 2009;170(2):244-256.
67. Hsu JY, Roy JA, Xie D, et al. Statistical Methods for Cohort Studies of CKD: Survival Analysis in the Setting of Competing Risks. Clin J Am Soc Nephrol. 2017;12(7):1181-1189.
68. Kuan IHS, Savage RL, Duffull SB, Walker RJ, Wright DFB. The Association between Metformin Therapy and Lactic Acidosis. Drug Saf. 2019;42(12):1449-1469.
69. Hung SC, Chang YK, Liu JS, et al. Metformin use and mortality in patients with advanced chronic kidney disease: national, retrospective, observational, cohort study. Lancet Diabetes Endocrinol. 2015;3(8):605-614.
70. van Dalem J, Brouwers MC, Stehouwer CD, et al. Risk of hypoglycaemia in users of sulphonylureas compared with metformin in relation to renal function and sulphonylurea metabolite group: population based cohort study. Bmj. 2016;354:i3625.
71. Ioannidis I. Diabetes treatment in patients with renal disease: Is the landscape clear enough? World J Diabetes. 2014;5(5):651-658.
72. Wu PC, Wu VC, Lin CJ, et al. Meglitinides increase the risk of hypoglycemia in diabetic patients with advanced chronic kidney disease: a nationwide, population-based study. Oncotarget. 2017;8(44):78086-78095.
73. Aguilar D. Heart Failure, Diabetes Mellitus, and Chronic Kidney Disease: A Clinical Conundrum. Circ Heart Fail. 2016;9(7):e003316.
74. Perkovic V, Toto R, Cooper ME, et al. Effects of Linagliptin on Cardiovascular and Kidney Outcomes in People With Normal and Reduced Kidney Function: Secondary Analysis of the CARMELINA Randomized Trial. Diabetes Care. 2020;43(8):1803-1812.
75. U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA adds warnings about heart failure risk to labels of type 2 diabetes medicines containing saxagliptin and alogliptin. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-adds-warnings-about-heart-failure-risk-labels-type-2-diabetes. Accessed July 2, 2020.
76. Udell JA, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes and moderate or severe renal impairment: observations from the SAVOR-TIMI 53 Trial. Diabetes Care. 2015;38(4):696-705.
77. McMurray JJV, Ponikowski P, Bolli GB, et al. Effects of Vildagliptin on Ventricular Function in Patients With Type 2 Diabetes Mellitus and Heart Failure: A Randomized Placebo-Controlled Trial. JACC Heart Fail. 2018;6(1):8-17.
78. Sano M. Mechanism by which dipeptidyl peptidase-4 inhibitors increase the risk of heart failure and possible differences in heart failure risk. Journal of Cardiology. 2019;73(1):28-32.
79. Packer M. Worsening Heart Failure During the Use of DPP-4 Inhibitors: Pathophysiological Mechanisms, Clinical Risks, and Potential Influence of Concomitant Antidiabetic Medications. JACC: Heart Failure. 2018;6(6):445-451.
80. Koyani CN, Trummer C, Shrestha N, et al. Saxagliptin but Not Sitagliptin Inhibits CaMKII and PKC via DPP9 Inhibition in Cardiomyocytes. Front Physiol. 2018;9:1622.
81. Deacon CF, Lebovitz HE. Comparative review of dipeptidyl peptidase-4 inhibitors and sulphonylureas. Diabetes Obes Metab. 2016;18(4):333-347.
82. Darsalia V, Ortsäter H, Olverling A, et al. The DPP-4 Inhibitor Linagliptin Counteracts Stroke in the Normal and Diabetic Mouse Brain. A Comparison With Glimepiride. 2013;62(4):1289-1296.
83. Shannon RP. DPP-4 Inhibition and Neuroprotection: Do Mechanisms Matter? Diabetes. 2013;62(4):1029-1031.
84. Malmgren S, Ahrén B. DPP-4 inhibition contributes to the prevention of hypoglycaemia through a GIP-glucagon counterregulatory axis in mice. Diabetologia. 2015;58(5):1091-1099.
85. Cho YY, Cho SI. Metformin combined with dipeptidyl peptidase-4 inhibitors or metformin combined with sulfonylureas in patients with type 2 diabetes: A real world analysis of the South Korean national cohort. Metabolism. 2018;85:14-22.
86. Ou HT, Chang KC, Li CY, Wu JS. Comparative cardiovascular risks of dipeptidyl peptidase 4 inhibitors with other second- and third-line antidiabetic drugs in patients with type 2 diabetes. Br J Clin Pharmacol. 2017;83(7):1556-1570.
87. Ou SM, Shih CJ, Chao PW, et al. Effects on Clinical Outcomes of Adding Dipeptidyl Peptidase-4 Inhibitors Versus Sulfonylureas to Metformin Therapy in Patients With Type 2 Diabetes Mellitus. Ann Intern Med. 2015;163(9):663-672.
88. Salvo F, Moore N, Arnaud M, et al. Addition of dipeptidyl peptidase-4 inhibitors to sulphonylureas and risk of hypoglycaemia: systematic review and meta-analysis. Bmj. 2016;353:i2231.
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