SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials

The Lancet

Volumn 393, Issue 10166, 2019, Pages 31-39

  Zelniker, Thomas A ^a   Wiviott, Stephen D ^a   Raz, Itamar ^b   Im, Kyungah ^a   Goodrich, Erica L ^a   Bonaca, Marc P ^a   Mosenzon, Ofri ^b   Kato, Eri T ^c   Cahn, Avivit ^b   Furtado, Remo H M ^a   Bhatt, Deepak L ^a   Leiter, Lawrence A ^d   McGuire, Darren K ^e   Wilding, John P H ^f   Sabatine, Marc S ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^c KYOTO UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^d ST MICHAEL'S HOSPITAL   (Canada)

^e UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^f UNIVERSITY OF LIVERPOOL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR;

ARTICLE; CAUSE OF DEATH; CEREBROVASCULAR ACCIDENT; CORONARY ARTERY ATHEROSCLEROSIS; DISEASE COURSE; ESTIMATED GLOMERULAR FILTRATION RATE; FOLLOW UP; HEART FAILURE; HEART INFARCTION; HOSPITALIZATION; HUMAN; KIDNEY DISEASE; KIDNEY FUNCTION; NON INSULIN DEPENDENT DIABETES MELLITUS; PRACTICE GUIDELINE; PRIMARY PREVENTION; PRIORITY JOURNAL; RISK REDUCTION; SECONDARY PREVENTION; SYSTEMATIC REVIEW; CARDIOVASCULAR DISEASE; COMPLICATION; DIABETIC NEPHROPATHY; META ANALYSIS; PROCEDURES;

CARDIOVASCULAR DISEASES; DIABETES MELLITUS, TYPE 2; DIABETIC NEPHROPATHIES; HUMANS; PRIMARY PREVENTION; SECONDARY PREVENTION; SODIUM-GLUCOSE TRANSPORTER 2 INHIBITORS;

EID: 85059501499     PISSN: 01406736     EISSN: 1474547X     Source Type: Journal    
DOI: 10.1016/S0140-6736(18)32590-X     Document Type: Article

References (40)

1. Zinman, B, Wanner, C, Lachin, JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 373 (2015), 2117–2128.
2. Neal, B, Perkovic, V, Mahaffey, KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 377 (2017), 644–657.
3. Wiviott, SD, Raz, I, Bonaca, MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med, 2018 published online Nov 10. DOI:10.1056/NEJMoa1812389.
4. US Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research. Guidance for industry: diabetes mellitus evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes, 2008, US Food and Drug Administration, Silver Spring, MD.
5. Piepoli, MF, Hoes, AW, Agewall, S, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: the Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J 37 (2016), 2315–2381.
6. American Diabetes Association. 8. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes—2018. Diabetes Care 41:suppl 1 (2018), S73–S85.
7. Wanner, C, Inzucchi, SE, Lachin, JM, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 375 (2016), 323–334.
8. Perkovic, V, Zeeuw, D, Mahaffey, KW, et al. Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials. Lancet Diabetes Endocrinol 6 (2018), 691–704.
9. Radholm, K, Figtree, G, Perkovic, V, et al. Canagliflozin and heart failure in type 2 diabetes mellitus: results from the CANVAS Program (Canagliflozin Cardiovascular Assessment Study). Circulation, 2018 published online March 11. DOI:10.1161/CIRCULATIONAHA.118.034222.
10. Neuen, BL, Ohkuma, T, NeHBal, B, et al. Cardiovascular and renal outcomes with canagliflozin according to baseline kidney function: data from the CANVAS Program. Circulation, 2018 published online June 25. DOI:10.1161/CIRCULATIONAHA.118.035901.
11. Wanner, C, Lachin, JM, Inzucchi, SE, et al. Empagliflozin and clinical outcomes in patients with type 2 diabetes mellitus, established cardiovascular disease, and chronic kidney disease. Circulation 137 (2018), 119–129.
12. Chang, HY, Singh, S, Mansour, O, Baksh, S, Alexander, GC, Association between sodium-glucose cotransporter 2 inhibitors and lower extremity amputation among patients with type 2 diabetes. JAMA Intern Med 178 (2018), 1190–1198.
13. Alba, M, Xie, J, Fung, A, Desai, M, The effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on mineral metabolism and bone in patients with type 2 diabetes mellitus. Curr Med Res Opin 32 (2016), 1375–1385.
14. Bonner, C, Kerr-Conte, J, Gmyr, V, et al. Inhibition of the glucose transporter SGLT2 with dapagliflozin in pancreatic alpha cells triggers glucagon secretion. Nat Med 21 (2015), 512–517.
15. US Food and Drug Administration. https://www.fda.gov/downloads/Drugs/DrugSafety/UCM446954.pdf FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood. 2015. (Accessed 4 June 2018)
16. Garg, SK, Henry, RR, Banks, P, et al. Effects of sotagliflozin added to insulin in patients with type 1 diabetes. N Engl J Med 377 (2017), 2337–2348.
17. Hutton, B, Salanti, G, Caldwell, DM, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med 162 (2015), 777–784.
18. Moher, D, Shamseer, L, Clarke, M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev, 4, 2015, 1.
19. Shamseer, L, Moher, D, Clarke, M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ, 350, 2015, g7647.
20. Hartung, J, Knapp, G, A refined method for the meta-analysis of controlled clinical trials with binary outcome. Stat Med 20 (2001), 3875–3889.
21. Higgins, JP, Altman, DG, Gotzsche, PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ, 343, 2011, d5928.
22. Higgins, JP, Thompson, SG, Deeks, JJ, Altman, DG, Measuring inconsistency in meta-analyses. BMJ 327 (2003), 557–560.
23. Viechtbauer, W, Conducting meta-analyses in r with the metafor package. J Stat Softw, 36, 2010, 48.
24. Fitchett, D, Zinman, B, Wanner, C, et al. Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME(R) trial. Eur Heart J 37 (2016), 1526–1534.
25. Mahaffey, KW, Neal, B, Perkovic, V, et al. Canagliflozin for primary and secondary prevention of cardiovascular events: results from the CANVAS Program (Canagliflozin Cardiovascular Assessment Study). Circulation 137 (2018), 323–334.
26. Monami, M, Dicembrini, I, Mannucci, E, Effects of SGLT-2 inhibitors on mortality and cardiovascular events: a comprehensive meta-analysis of randomized controlled trials. Acta Diabetol 54 (2017), 19–36.
27. Zelniker, TA, Braunwald, E, Cardiac and renal effects of sodium-glucose co-transporter 2 inhibitors in diabetes: JACC state-of-the-art review. J Am Coll Cardiol 72 (2018), 1845–1855.
28. Scheen, AJ, Pharmacokinetic and pharmacodynamic profile of empagliflozin, a sodium glucose co-transporter 2 inhibitor. Clin Pharmacokinet 53 (2014), 213–225.
29. Devineni, D, Polidori, D, Clinical pharmacokinetic, pharmacodynamic, and drug-drug interaction profile of canagliflozin, a sodium-glucose co-transporter 2 inhibitor. Clin Pharmacokinet 54 (2015), 1027–1041.
30. Advance Collaborative Group, Patel, A, MacMahon, S, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 358 (2008), 2560–2572.
31. Cherney, DZ, Perkins, BA, Soleymanlou, N, et al. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation 129 (2014), 587–597.
32. Heerspink, HJ, Perkins, BA, Fitchett, DH, Husain, M, Cherney, DZ, Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: cardiovascular and kidney effects, potential mechanisms, and clinical applications. Circulation 134 (2016), 752–772.
33. Scheen, AJ, Pharmacodynamics, efficacy and safety of sodium-glucose co-transporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus. Drugs 75 (2015), 33–59.
34. Thong, KY, Yadagiri, M, Barnes, DJ, et al. Clinical risk factors predicting genital fungal infections with sodium-glucose cotransporter 2 inhibitor treatment: the ABCD nationwide dapagliflozin audit. Prim Care Diabetes 12 (2018), 45–50.
35. Nyirjesy, P, Sobel, JD, Fung, A, et al. Genital mycotic infections with canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus: a pooled analysis of clinical studies. Curr Med Res Opin 30 (2014), 1109–1119.
36. Garg, SK, Peters, AL, Buse, JB, Danne, T, Strategy for mitigating DKA risk in patients with type 1 diabetes on adjunctive treatment with SGLT Inhibitors: a STICH protocol. Diabetes Technol Ther 20 (2018), 571–575.
37. Goldenberg, RM, Berard, LD, Cheng, AY, et al. SGLT2 inhibitor-associated diabetic ketoacidosis: clinical review and recommendations for prevention and diagnosis. Clin Ther 38 (2016), 2654–2664.
38. Zinman, B, Inzucchi, SE, Lachin, JM, et al. Empagliflozin and cerebrovascular events in patients with type 2 diabetes mellitus at high cardiovascular risk. Stroke 48 (2017), 1218–1225.
39. Cavender, MA, Steg, PG, Smith, SC Jr, et al. Impact of diabetes mellitus on hospitalization for heart failure, cardiovascular events, and death: outcomes at 4 years from the REduction of Atherothrombosis for Continued Health (REACH) registry. Circulation 132 (2015), 923–931.
40. Rawshani, A, Rawshani, A, Franzen, S, et al. Mortality and cardiovascular disease in type 1 and type 2 diabetes. N Engl J Med 376 (2017), 1407–1418.