Dipeptidyl peptidase 4 (DPP-4) inhibitors and cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM): a systematic review and meta-analysis

Springer Science and Business Media LLC - Tập 20 - Trang 1-9 - 2019
Dan Liu1, Biao Jin2, Wei Chen2, Peng Yun1
1Department of Endocrinology, Jingzhou First Peoples Hospital, Jingzhou, People’s Republic of China
2Department of Critical Care Medicine, Jingzhou First Peoples Hospital, Jingzhou, People’s Republic of China

Tóm tắt

Dipeptidyl peptidase 4 (DPP-4) inhibitors are newer oral anti-diabetic agents which have been approved by the Food and Drug Administration for the treatment of patients with type 2 diabetes mellitus (T2DM). In this analysis, we aimed to systematically compare the cardiovascular outcomes associated with DPP-4 inhibitors versus non-DPP-4 inhibitor users. All English publications that compared the use of DPP-4 inhibitors and that reported cardiovascular outcomes in patients with T2DM were searched using specific terms. Studies were included if they satisfied the following inclusion criteria: They were randomized trials or observation cohorts/registries comparing DPP-4 inhibitors use in patients with T2DM; The studies included a large sample size of participants; And they reported cardiovascular outcomes as their main endpoints. RevMan 5.3 was used to analyze the data, and odds ratios (OR) with 95% confidence intervals (CI) were used to represent the results. A total number of 157,478 participants with T2DM were included. Seventy-six thousand and twenty six patients were assigned to the DPP-4 inhibitor group whereas 81,452 patients were assigned to the control group. Results of the current analysis showed that during a mean follow-up time period ranging from 52 to 152 weeks, the primary endpoint (cardiovascular death/non-fatal myocardial infarction (MI)/non-fatal stroke) was not significantly different in the treatment of T2DM patients with versus without DPP-4 inhibitors (OR: 0.95, 95% CI: 0.86–1.04; P = 0.26). Cardiovascular death (OR: 1.00, 95% CI: 0.90–1.10; P = 0.93), stroke (OR: 1.03, 95% CI: 0.89–1.18; P = 0.72), MI (OR: 0.97, 95% CI: 0.88–1.07; P = 0.59), all-cause mortality (OR: 0.84, 95% CI: 0.59–1.18; P = 0.31), hospitalization for cardiovascular complications (OR: 1.02, 95% CI: 0.96–1.09; P = 0.45) and hospitalization specifically for heart failure (OR: 1.05, 95% CI: 0.90–1.23; P = 0.55) were also similarly manifested in both groups. The current analysis showed that treatment with DPP-4 inhibitors did not significantly increase cardiovascular outcomes in these patients with T2DM indicating that those drugs might be safe to use in terms of cardiovascular events.

Tài liệu tham khảo

Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, de Ferranti SD, Floyd J, Fornage M, Gillespie C, Isasi CR, Jiménez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Mackey RH, Matsushita K, Mozaffarian D, Mussolino ME, Nasir K, Neumar RW, Palaniappan L, Pandey DK, Thiagarajan RR, Reeves MJ, Ritchey M, Rodriguez CJ, Roth GA, Rosamond WD, Sasson C, Towfighi A, Tsao CW, Turner MB, Virani SS, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P, American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke Statistics-2017 update: a report from the American Heart Association. Circulation. 2017;135(10):e146–603. Lago RM, Singh PP, Nesto RW. Congestive heart failure and cardiovascular death in patients with prediabetes and type 2diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials. Lancet. 2007;370(9593):1129–36. Hiatt WR, Kaul S, Smith RJ. The cardiovascular safety of diabetes drugs--insights from the rosiglitazone experience. N Engl J Med. 2013;369(14):1285–7. Zhong J, Maiseyeu A, Davis SN, Rajagopalan S. DPP4 in cardio-metabolic disease: recent insights from the laboratory and clinical trials of DPP4 inhibition. Circ Res. 2015;116(8):1491–504. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcareinterventions: explanation and elaboration. BMJ. 2009;339:b2700. Higgins JP, et al. Assessing risk of bias in included studies. In: Cochrane handbook for systematic reviews of interventions: Wiley; 2008. p. 187–241. Gantz I, Chen M, Suryawanshi S, Ntabadde C, Shah S, O'Neill EA, Engel SS, Kaufman KD, Lai E. A randomized, placebo-controlled study of the cardiovascular safety of the once-weekly DPP-4inhibitor omarigliptin in patients with type 2 diabetes mellitus. Cardiovasc Diabetol. 2017;16(1):112. Green JB, Bethel MA, Armstrong PW, Buse JB, Engel SS, Garg J, Josse R, Kaufman KD, Koglin J, Korn S, Lachin JM, McGuire DK, Pencina MJ, Standl E, Stein PP, Suryawanshi S, Van de Werf F, Peterson ED, Holman RR, TECOS Study Group. Effect of Sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;373(3):232–42. Park HE, Jeon J, Hwang IC, Sung J, Lee SP, Kim HK, Cho GY, Sohn DW, Kim YJ. Effect of dipeptidyl Peptidase-4 inhibitor on all-cause mortality and coronary Revascularizationin diabetic patients. J Cardiovasc Ultrasound. 2015;23(4):233–43. 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(14):1317–26. Shih CJ, Chen HT, Kuo SC, Ou SM, Chen YT. Cardiovascular outcomes of dipeptidyl Peptidase-4 inhibitors in elderly patients with type 2 diabetes: a Nationwide study. J Am Med Dir Assoc. 2016;17(1):59–64. Wang SH, Chen DY, Lin YS, Mao CT, Tsai ML, Hsieh MJ, Chou CC, Wen MS, Wang CC, Hsieh IC, Hung KC, Chen TH. Cardiovascular outcomes of Sitagliptin in type 2 diabetic patients with acute MyocardialInfarction, a population-based cohort study in Taiwan. PLoS One. 2015;10(6):e0131122. 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(14):1327–35. Krishna R, Addy C, Tatosian D, Glasgow XS, Gendrano Iii IN, Robberechts M, Haazen W, de Hoon JN, Depré M, Martucci A, Peng JZ, Johnson-Levonas AO, Wagner JA, Stoch SA. Pharmacokinetics and pharmacodynamics of Omarigliptin, a once-weekly dipeptidyl Peptidase-4 (DPP-4) inhibitor, after single and multiple doses in healthy subjects. J Clin Pharmacol. 2016;56(12):1528–37. Li YR, Tsai SS, Chen DY, Chen ST, Sun JH, Chang HY, Liou MJ, Chen TH. Linagliptin and cardiovascular outcomes in type 2 diabetes after acute coronary syndrome or acute ischemic stroke. Cardiovasc Diabetol. 2018;17(1):2. Rosenstock J, Perkovic V, Alexander JH, Cooper ME, Marx N, Pencina MJ, Toto RD, Wanner C, Zinman B, Baanstra D, Pfarr E, Mattheus M, Broedl UC, Woerle HJ, George JT, von Eynatten M, McGuire DK, CARMELINA® investigators. Rationale, design, and baseline characteristics of the CArdiovascular safety and renal microvascular outcomE study with LINAgliptin (CARMELINA®): a randomized, double-blind, placebo-controlled clinical trial in patients with type 2 diabetes and high cardio-renal risk. Cardiovasc Diabetol. 2018;17(1):39.