1. Journal Club 埼玉医科大学 総合医療センター 内分泌・糖尿病内科 Department of Endocrinology and Diabetes, Saitama Medical Center, Saitama Medical University 松田 昌文 Matsuda, Masafumi 2015 年 10 月 29 日 8:30-8:55 ８階 医局 Ou SM, Shih CJ, Chao PW, Chu H, Kuo SC, Lee YJ, Wang SJ, Yang CY, Lin CC, Chen TJ, Tarng DC, Li SY, Chen YT. 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 Oct 13. doi: 10.7326/M15-0308.

2. DPP4 阻害薬、 GLP-1 受容体作動薬、 SGLT2 阻害薬の心血管障害への影響 1.Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desai NR, Mosenzon O, McGuire DK, Ray KK, Leiter LA, Raz I; SAVOR- TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013;369:1317–1326. 2.White WB, Cannon CP, Heller SR, Nissen SE, Bergenstal RM, Bakris GL, Perez AT, Fleck PR, Mehta CR, Kupfer S, Wilson C, Cushman WC, Zannad F; EXAMINE Investigators. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 2013;369:1327–1335. European Heart Journal doi:10.1093/eurheartj/ehv239 12

3. From National Yang-Ming University, Taipei Veterans General Hospital, Taipei Medical University, Taipei City Hospital, Ren Ai Branch, and Taipei City Hospital, Heping Fuyou Branch, Taipei, Taiwan; Taipei Veterans General Hospital, Yuanshan Branch, Yilan, Taiwan; and National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County, Taiwan. Ann Intern Med. 2015 Oct 13. doi: 10.7326/M15-0308.

4. Background: Recent studies concluded that dipeptidyl peptidase-4 (DPP-4) inhibitors provide glycemic control but also raised concerns about the risk for heart failure in patients with type 2 diabetes mellitus (T2DM). However, large-scale studies of the effects on cardiovascular outcomes of adding DPP-4 inhibitors versus sulfonylureas to metformin therapy remain scarce.

5. Objective: To compare clinical outcomes of adding DPP-4 inhibitors versus sulfonylureas to metformin therapy in patients with T2DM. Design: Nationwide study using Taiwan's National Health Insurance Research Database. Setting: Taiwan. Patients: All patients with T2DM aged 20 years or older between 2009 and 2012. A total of 10 089 propensity score– matched pairs of DPP-4 inhibitor users and sulfonylurea users were examined. Measurements: Cox models with exposure to sulfonylureas and DPP-4 inhibitors included as time-varying covariates were used to compare outcomes. The following outcomes were considered: all-cause mortality, major adverse cardiovascular events (MACEs) (including ischemic stroke and myocardial infarction), hospitalization for heart failure, and hypoglycemia. Patients were followed until death or 31 December 2013.

23. Results: DPP-4 inhibitors were associated with lower risks for all-cause death (hazard ratio [HR], 0.63 [95% CI, 0.55 to 0.72]), MACEs (HR, 0.68 [CI, 0.55 to 0.83]), ischemic stroke (HR, 0.64 [CI, 0.51 to 0.81]), and hypoglycemia (HR, 0.43 [CI, 0.33 to 0.56]) compared with sulfonylureas as add- on therapy to metformin but had no effect on risks for myocardial infarction and hospitalization for heart failure.

24. Limitation: Observational study design. Conclusion: Compared with sulfonylureas, DPP-4 inhibitors were associated with lower risks for all-cause death, MACEs, ischemic stroke, and hypoglycemia when used as add-ons to metformin therapy. Primary Funding Source: None.

25. Message 傾向スコアでマッチさせた 2 型糖尿病患者約 1 万 組を対象に、メトホルミン療法へのジペプチジル ペプチダーゼ -4 （ DPP-4 ）阻害薬またはスルホ ニル尿素（ SU ）薬の上乗せ効果を比較。 DPP-4 阻害薬は SU 薬に比べ全死亡 / 主要有害心血管イベ ント / 虚血性脳卒中 / 低血糖リスク低下と関連し た（ハザード比 0.63 [95% CI, 0.55 - 0.72] 、 0.68[CI, 0.55 - 0.83] 、 0.64[CI, 0.51 - 0.81] 、 0.43[CI, 0.33 - 0.56] ）。 http://www.m3.com/clinical/journal/15923