•  
  •  
 

Abstract

Type 2 diabetes mellitus (DMT2) patients are associated with an increased risk of cardiovascular events. Prior to the era of cardio-vascular trial outcome (CVOT) evidence on the efficacy of old oral diabetes (OAD) drugs such as metformin, sulfonylurea, thiazolidindion, glinid, and alpha glucosidase inhibitors in reducing the risk of cardiovascular events was very limited. Since 2008, all OADs must have CVOT data. DPP-4 inhibitors are neutral against the risk of cardiovascular events while SGLT-2 inhibitors are reported to significantly reduce the risk of cardiovascular events. This finding even helped to change the DMT2 management guidelines issued by American Diabetes Association (ADA-EASD) in late 2018. However, SGLT-2 inhibitor applications in Indonesia are likely to be constrained in terms of costs. When compared with an intensive multifactorial approach that seeks to reduce blood glucose, lipids, blood pressure, weight, and aspirin; it turns out that this multifactorial approach is associated with a lower risk of higher cardiovascular events and lower costs. In the JKN era, where quality control and cost control are needed, it seems that the multifactorial approach will still be the main choice in reducing cardiovascular events in people with T2DM in Indonesia.

References

1. Kementerian Kesehatan RI. Infodatin: situasi dan analisis diabetes [Internet]. 2014 [cited 2018 Nov 14]. Available from: http://www. depkes.go.id/resources/download/pusdatin/infodatin/infodatindiabetes.pdf 2. Fei Y, Tsoi MF, Kumana CR, Cheung TT, Cheung BMY. Network metaanalysis of cardiovascular outcomes in randomized controlled trials of new antidiabetic drugs. Int J Cardiol. 2018;254(2018):291-6. 3. Savarese G, D’Amore C, Federici M, Martino FD, Dellegrottaglie S, Marciano C, et al. Effects of dipeptidyl peptidase 4 inhibitors and sodium-glucose linked cotransporter-2 inhibitors on cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis. Int J Cardiol. 2016;220(2016):595-601. 4. Marfella R, Sasso FC, Cacciapuoti F, Portoghese M, Rizzo MR, Siniscalchi M, et al. Tight glycemic control may increase regenerative potential of myocardium during acute infarction. J Clin Endocrinol Metab. 2012; 97(3):933-42. 5. Moodahadu LS, Dhall R, Zargar AH, Bangera S, Ramani L, Katipally R. Tight glycemic control and cardiovascular effects in type 2 diabetic patients. Heart Views. 2014;15(4):111-20. 6. Mannucci E. Is glucose control important for prevention of cardiovascular disease in diabetes? Diabetes Care. 2013;36(2):259- 63. 7. PB PERKENI. Konsensus pengelolaan dan pencegahan diabetes melitus tipe 2 di Indonesia 2015 [Internet]. Available from: https:// kupdf.net/download/konsensus-penggunaan-insulin-perkeni2015_590b19d0dc0d60cd4a959ecc_pdf 8. Roumie CL, Min JY, McGowan LD, Presley C, Grijalva CG, Hackstadt AJ. Comparative safety of sulfonylurea and metformin monotherapy on the risk of heart failure: a cohort study. J Am Heart Assoc. 2018; 6(4):e005379. 9. Davies MJ, D’Alessio DA, Fradkin J, Kernan WN, Mathieu C, Mingrone G, et al. Management of hyperglycaemia 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. 2018;41(12):1-38. 10. Griffin SJ, Leaver JK, Irving GJ. Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes. Diabetologia. 2017;60(9):1620-9. 11. Lamanna C, Monami M, Marchionni N, Mannucci E. Effect of metformin on cardiovascular events and mortality: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2011;13(3):221- 8. 12. Fung CSC, Wan EYF, Wong CKH, Jiao F, Chan AKC. Effect of metformin monotherapy on cardiovascular diseases and mortality: a retrospective cohort study on chinese type 2 diabetes mellitus patients. Cardiovasc Diabetol. 2015;14:137. 13. Roumie CL, Hung AM, Greevy RA. Comparative effectiveness of sulfonylurea and metformin monotherapy on cardiovascular events in type 2 diabetes mellitus: a cohort study. Ann Intern Med. 2012;157(9):601-2. 14. Sola D, Rossi L, Schianca GP. Sulfonylureas and their use in clinical practice. Arch Med Sci. 2015;11(4):840-8. 15. Heller SR. A summary of the ADVANCE trial. Diabetes Care. 2009;32(2):357-61. 16. Azoulay L, Suissa S. Sulfonylureas and the risks of cardiovascular events and death: a methodological meta-regression analysis of the observational studies. Diabetes Care. 2017;40:706-14. 17. Rutten G. Effect of nateglinide on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010;362:16. 18. Charbonnel B, Dormandy J, Erdmann E, Massi-Benedetti M, Skene A. The prospective pioglitazone clinical trial in macrovascular events (PROactive). Diabetes Care. 2004;27(7):1-7. 19. Dormandy JA, Charbonne B, Eckland DJA, Erdmann E, MassiBenedetti M, Moules IK, et al. Secondary prevention of macrovascular events in patiens with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 2005;366:1-11. 20. Chen JM, Chang CW, Lin YC, Horng JT, H.-H. Sheu W. acarbose treatment and the risk of cardiovascular disease in type 2 diabetic patients: a nationwide seven-year follow-up study. J Diabetes Res. 2014;2014:1-6. 21. Hanefeld M, Catagay M, Petrowitsch T, Neuser D, Petzinna D, Rupp M. Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients: meta-analysis of seven long-term studies. Eur Heart J. 2004;25:10-6. 22. Chang CH, Chang YC, Lin JW, Chen ST, Chuang LM, Lai MS. Cardiovascular risk associated with acarbose versus metformin as the first-line treatment in patients with type 2 diabetes: a nationwide cohort study. J Clin Endocrinol Metab. 2015;100(3):1121-9. 23. Thompson PL, Davis TME. Review cardiovascular effects of glucoselowering therapies for type 2 diabates: new drugs in perspective. Clin Ther. 2017;39(5):1012-25. 24. Elgendy IY, Mahmoud AN, Barakat AF, Elgendy AY, Saad M, Abuzid A, et al. Cardiovascular safety of dipeptidyl-peptidase iv inhibitors: a meta-analysis of placebo-controlled randomized trials. Am J Cardiovasc Drugs. 2017;17:143-55. 25. Nishikido T, Oyama JI, Ohira H, Node K. The effects and safety of vildagliptin on cardiac function after acute myocardial infarction. Int J Cardiol. 2015;188(2015):13-5. 26. Gokhale M, Buse JB, Funk MJ, Lund J, Pate V, Simpson RJ, et al. No increased risk of cardiovascular events in older adults initiating dipeptidyl peptidase 4 inhibitors versus therapeutic alternatives. Diabetes Obes Metab. 2017;19(7):970-80. 27. Cinti F, Moffa S, Impronta F, et al. Spotlight on ertugliflozin and its potential in the treatment of type 2 diabetes: evidence to date. Drug Des Devel Ther. 2017;11:2905-19. 28. Zelniker M, Lam CSP, Kohsaka S, Kim DJ, Karasik A, Shaw J et al. Cardiovascular events associated with sglt-2 inhibitors versus other glucose-lowering drugs: the CVD-REAL 2 study. J Am Coll Cardiol. 2018;71(23):2628-39. . Neal B, Perkovic V, Mahaffey KW, Zeeuw D, Fulcher G, Erondu N, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377:7. 30. Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2018;83:1-12. 31. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:22. 32. Andayani TM. Analisis biaya terapi diabetes mellitus di Rumah Sakit Dr. Sardjito Yogyakarta. Majalah Farmasi Indonesia.2006;17(3):130-5 33. Acharya KG, Shah KN, Solanki ND, Rana DA. Evaluation of antidiabetic prescriptions, cost and adherence to treatment guidelines: A prospective, cross-sectional study at a tertiary care teaching hospital. J Basic Clin Pharm. 2013; 4(4):82-7. 34. Andayani TM, Imaningsih I. Cost analysis of antidiabetic drugs for diabetes mellitus outpatient in kodya Yogyakarta hospital. Malays. J Pharm Sci. 2007;5(1):19-23. 35. Pribadi F, Permana I. Analysis of the cost-effectiveness of antidiabetic drugs among self paid participant of the Indonesia national security service (NSS) with type 2 diabetes mellitus. Int J Med Sci Public Health.2018; 8(3): 108-11 36. George N, Kumar A, Amma V. Glycemic control and costeffectiveness attained by the drug utilization of oral antidiabetic agents in a tertiary care hospital in South India. Int J Basic Clin Pharmacol. 2016;5(3):684-91. 37. Gaede P, Vedel P, Larsen N, Jensen GVH. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003;348:383-93. 38. Gaede J, Oellgaard J, Ibsen R, Gaede P, Nortoft E, Parving HH, et al. A cost analysis of intensified vs conventional multifactorial therapy in individuals with type 2 diabetes: a post hoc analysis of the steno-2 study. Diabetologia. 2019;62(1):147-55

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.