Glycemia control and glucose-lowering therapy in patients with type 2 diabetes mellitus and cardiovascular disease (review of multicenter randomized trials)
https://doi.org/10.14341/DM2003422-27
Abstract
The use of modern pharmaceuticals and cardiovascular disease (CVD) treatment methods has increased life expectancy and improved the quality of life of both patients with normal carbohydrate metabolism and diabetes mellitus (DM). This study provides a review of the literature on glycaemic control and choice of glucose-lowering therapy in patients with type 2 DM (T2DM) and CVD. According to the latest recommendations for the prevention of CVD, the target level of glycated haemoglobin (HbA1c) should be less than 7.0% and 7.5%–8.0% in older patients to decrease the risk of hypoglycaemia. The target blood glucose level is 7.7–10 mmol/L. The results of randomized clinical trials (RCTs) revealed that the adverse effects of second-generation sulfonylureas include critical hypoglycaemia episodes and increases in CVD-associated complications and mortality. Metformin reduces the risk of CVD in comparison with second-generation sulfonylurea derivates and insulin. Thiazolidinediones are not currently used for patients with CVD, and the safety of GLP-1 analogues and SGLT-2 inhibitors is still under investigation. When metformin therapy is ineffective, DPP-4 inhibitors should be prescribed and renal function should be monitored. Metformin is contra-indicated in patients with severe chronic heart failure (CHF) and acute myocardial infarction (AMI) because of the risk of lactic acidosis with tissue hypoxia. Thus, insulin is the drug of choice for glycaemic control in CVD patients with chronic kidney disease, severe heart failure or other acute clinical conditions.
About the Authors
Sergey V. KakorinRussian Federation
MD, PhD
Competing Interests: No confict of interest
Ruben A. Iskandaryan
Russian Federation
PhD
Competing Interests: No conflict of interest
Ashot M. Mkrtumyan
Russian Federation
MD, PhD, Professor
Competing Interests: No conflict of interest
References
1. Malmberg K, Rydén L, Efendic S, et al. Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): Effects on mortality at 1 year. Am J Cardiol. 1995;26(1):57-65. doi: 10.1016/0735-1097(95)00126-k
2. Malmberg K. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. Bmj. 1997;314(7093):1512-1512. doi: 10.1136/bmj.314.7093.1512
3. Malmberg K, Rydén L, Wedel H. Intense Metabolic Control by Means of Insulin in Patients With Diabetes Mellitus and Acute Myocardial Infarction (DIGAMI 2): Effects on Mortality and Morbidity. ACC Current Journal Review. 2005;14(7):6. doi: 10.1016/j.accreview.2005.06.015
4. Mellbin LG, Malmberg K, Norhammar A, et al. Prognostic implications of glucose-lowering treatment in patients with acute myocardial infarction and diabetes: experiences from an extended follow-up of the Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Study. Diabetologia. 2011;54(6):1308-1317. doi: 10.1007/s00125-011-2084-x
5. Dormandy JA, Charbonnel B, Eckland DJA, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. The Lancet. 2005;366(9493):1279-1289. doi: 10.1016/s0140-6736(05)67528-9.
6. Group AC, Patel A, MacMahon S, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560-2572. doi: 10.1056/NEJMoa0802987.
7. Group AC, Patel A, MacMahon S, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560-2572. doi: 10.1056/NEJMoa0802987.
8. Control G, Turnbull FM, Abraira C, et al. Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia. 2009;52(11):2288-2298. doi: 10.1007/s00125-009-1470-0
9. Duckworth W, Abraira C, Moritz T. Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes. Journal of Vascular Surgery. 2009;49(4):1084. doi: 10.1016/j.jvs.2009.02.026
10. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). The Lancet. 1998;352(9131):854-865. doi: 10.1016/s0140-6736(98)07037-8
11. Miller ME, Williamson JD, Gerstein HC, et al. Effects of randomization to intensive glucose control on adverse events, cardiovascular disease, and mortality in older versus younger adults in the ACCORD Trial. Diabetes Care. 2014;37(3):634-643. doi: 10.2337/dc13-1545
12. Group AS, Gerstein HC, Miller ME, et al. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med. 2011;364(9):818-828. doi: 10.1056/NEJMoa1006524
13. Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M, et al. Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials. BMJ. 2011;343:d4169. doi: 10.1136/bmj.d4169
14. Zoungas S, Patel A, Chalmers J, et al. Severe hypoglycemia and risks of vascular events and death. N Engl J Med. 2010;363(15):1410-1418. doi: 10.1056/NEJMoa1003795
15. Bravis V, Hui E, Salih S, et al. Ramadan Education and Awareness in Diabetes (READ) programme for Muslims with Type 2 diabetes who fast during Ramadan. Diabet Med. 2010;27(3):327-331. doi: 10.1111/j.1464-5491.2010.02948.x
16. Дедов И.И., Шестакова М.В., Галстян Г.Р., и др. Алгоритмы специализированной медицинской помощи больным сахарным диабетом. Под редакцией И.И. Дедова, М.В. Шестаковой (7-й выпуск) // Сахарный диабет. – 2015. – Т. ١٨. – №1S – C. 1-112. [Dedov II, Shestakova MV, Galstyan GR, et al. Standards of specialized diabetes care. Edited by Dedov I.I., Shestakova M.V. (7th edition).Diabetes mellitus. 2015;18(1S):1-112. (in Russ)] doi: 10.14341/DM20151S1-112
17. Verges B, Avignon A, Bonnet F, et al. Consensus statement on the care of the hyperglycaemic/diabetic patient during and in the immediate follow-up of acute coronary syndrome. Diabetes Metab.2012;38(2):113-127. doi: 10.1016/j.diabet.2011.11.003
18. Ritsinger V, Malmberg K, Mårtensson A, et al. Intensified insulin-based glycaemic control after myocardial infarction: mortality during 20 year follow-up of the randomised Diabetes Mellitus Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI 1) trial. Lancet Diabetes Endocrinol. 2014;2(8):627-633. doi: 10.1016/s2213-8587(14)70088-9
19. Cummings J, Mineo K, Levy R, Josephson R. A Review of the DIGAMI Study: Intensive Insulin Therapy During and After Myocardial Infarctions in Diabetic Patients. Diabetes Spectrum. 1999;12(2):84-88.
20. Cheung NW, Wong VW, McLean M. The Hyperglycemia: Intensive Insulin Infusion In Infarction (HI-5) Study: A randomized controlled trial of insulin infusion therapy for myocardial infarction.Diabetes Care. 2006;29(4):765-770. doi: 10.2337/diacare.29.04.06.dc05-1894
21. Holman RR, Farmer AJ, Davies MJ, et al. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med. 2009;361(18):1736-1747. doi: 10.1056/NEJMoa0905479
22. Holman RR, Thorne KI, Farmer AJ, et al. Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes. N Engl J Med. 2007;357(17):1716-1730. doi: 10.1056/NEJMoa075392
23. Gan RM, Wong V, Cheung NW, McLean M. Effect of insulin infusion on electrocardiographic findings following acute myocardial infarction: importance of glycaemic control. Diabet Med.2009;26(2):174-176. doi: 10.1111/j.1464-5491.2008.02630.x
24. Raz I, Wilson PW, Strojek K, et al. Effects of prandial versus fasting glycemia on cardiovascular outcomes in type 2 diabetes: the HEART2D trial. Diabetes Care. 2009;32(3):381-386. doi: 10.2337/dc08-1671
25. Group BDS, Frye RL, August P, et al. A randomized trial of therapies for type 2 diabetes and coronary artery disease. N Engl J Med. 2009;360(24):2503-2515. doi: 10.1056/NEJMoa0805796
26. Investigators OT, Gerstein HC, Bosch J, et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012;367(4):319-328. doi: 10.1056/NEJMoa1203858
27. Taylor R. Digami too? Diabetologia. 2006;49(6):1134-1137. doi: 10.1007/s00125-006-0250-3
28. Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359(15):1577-1589. doi: 10.1056/NEJMoa0806470
29. Stratton IM, Cull CA, Adler AI, et al. Additive effects of glycaemia and blood pressure exposure on risk of complications in type 2 diabetes: a prospective observational study (UKPDS 75). Diabetologia.2006;49(8):1761-1769. doi: 10.1007/s00125-006-0297-1
30. Leslie RDG. United Kingdom Prospective Diabetes Study (UKPDS): what now or so what? Diabetes Metab Res Rev. 1999;15(1):65-71. doi: 10.1002/(SICI)1520-7560(199901/02)15:1<65::AID-DMRR3>3.0.CO;2-X
31. Monami M, Genovese S, Mannucci E. Cardiovascular safety of sulfonylureas: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2013;15(10):938-953. doi: 10.1111/dom.12116
32. Morgan CL, Mukherjee J, Jenkins-Jones S, et al. Association between first-line monotherapy with sulphonylurea versus metformin and risk of all-cause mortality and cardiovascular events: a retrospective, observational study. Diabetes Obes Metab. 2014;16(10):957-962. doi: 10.1111/dom.12302
33. Draeger KE, Wernicke-Panten K, Lomp HJ, et al. Long-term treatment of type 2 diabetic patients with the new oral antidiabetic agent glimepiride (Amaryl): a double-blind comparison with glibenclamide.Horm Metab Res. 1996;28(9):419-425. doi: 10.1055/s-2007-979830
34. Дедов И.И., Шестакова М.В., Аметов А.С., и др. Проект консенсус совета экспертов Российской ассоциации эндокринологов (РАЭ) по инициации и интенсификации сахароснижающей терапии сахарного диабета 2 типа? // Сахарный диабет. – 2011. – Т. 14. – №1 – C. 95-105. [Dedov II, Shestakova MV, Ametov AS, et al. Consensus statement by a panel of experts of the Russian Association of Endocrinologists (RAE) on initiation and intensificationof hypoglycemic therapy for type 2 diabetes mellitus. Diabetes mellitus. 2011;14(1):95-105. (in Russ)] doi: 10.14341/2072-0351-6256
35. Шаронова Л.А., Вербовой А.Ф., Косарева О.В. Роль препаратов сульфонилмочевины в лечении сахарного диабета ٢-го типа // Медицинский совет. – 2016. – №3 – С. 6-9. [Sharonova LA, Verbovoy AF, Kosareva OV. The role of sulfonylures in the treatment of type 2 diabetes. Meditsinskiy Sovet. 2016;(3):6-9. (in Russ)]
36. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356(24):2457-2471. doi: 10.1056/NEJMoa072761
37. Nissen SE, Wolski K. Rosiglitazone revisited: an updated meta-analysis of risk for myocardial infarction and cardiovascular mortality. Arch Intern Med. 2010;170(14):1191-1201. doi: 10.1001/archinternmed.2010.207
38. Home PD, Pocock SJ, Beck-Nielsen H, et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. The Lancet. 2009;373(9681):2125-2135. doi: 10.1016/s0140-6736(09)60953-3
39. Punthakee Z, Bosch J, Dagenais G, et al. Design, history and results of the Thiazolidinedione Intervention with vitamin D Evaluation (TIDE) randomised controlled trial. Diabetologia. 2012;55(1):36-45. doi: 10.1007/s00125-011-2357-4
40. Jayawardene D, Ward GM, O’Neal DN, et al. New treatments for type 2 diabetes: cardiovascular protection beyond glucose lowering? Heart Lung Circ. 2014;23(11):997-1008. doi: 10.1016/j.hlc.2014.05.007
41. Waugh N, Cummins E, Royle P, et al. Newer agents for blood glucose control in type 2 diabetes: systematic review and economic evaluation. Health Technol Assess. 2010;14(36). doi: 10.3310/hta14360
42. Muskiet MHA, van Raalte DH, van Bommel EJM, et al. Understanding EMPA-REG OUTCOME. Lancet Diabetes Endocrinol. 2015;3(12):928-929. doi: 10.1016/s2213-8587(15)00424-6
43. Rajasekeran H, Lytvyn Y, Cherney DZ. Sodium-glucose cotransporter 2 inhibition and cardiovascular risk reduction in patients with type 2 diabetes: the emerging role of natriuresis. Kidney Int.2016;89(3):524-526. doi: 10.1016/j.kint.2015.12.038
44. Scheen AJ. SGLT2 inhibition: efficacy and safety in type 2 diabetes treatment. Expert Opin Drug Saf. 2015;14(12):1879-1904. doi: 10.1517/14740338.2015.1100167
45. 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. doi: 10.1056/NEJMoa1305889
46. 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. doi: 10.1056/NEJMoa1307684
47. Seino Y, Hiroi S, Hirayama M, Kaku K. Efficacy and safety of alogliptin added to sulfonylurea in Japanese patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial with an open-label, long-term extension study. J Diabetes Investig. 2012;3(6):517-525. doi: 10.1111/j.2040-1124.2012.00226.x
48. Aziz KM. Fasting during Ramadan: efficacy, safety, and patient acceptability of vildagliptin in diabetic patients. Diabetes Metab Syndr Obes. 2015;8:207-211. doi: 10.2147/DMSO.S54683
49. Patil HR, Al Badarin FJ, Al Shami HA, et al. Meta-analysis of effect of dipeptidyl peptidase-4 inhibitors on cardiovascular risk in type 2 diabetes mellitus. Am J Cardiol. 2012;110(6):826-833. doi: 10.1016/j.amjcard.2012.04.061
50. 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. doi: 10.1056/NEJMoa1501352
51. Mogensen UM, Andersson C, Fosbol EL, et al. Cardiovascular safety of combination therapies with incretin-based drugs and metformin compared with a combination of metformin and sulphonylurea in type 2 diabetes mellitus--a retrospective nationwide study. Diabetes Obes Metab. 2014;16(10):1001-1008. doi: 10.1111/dom.12314
52. Morgan CL, Mukherjee J, Jenkins-Jones S, et al. Combination therapy with metformin plus sulphonylureas versus metformin plus DPP-4 inhibitors: association with major adverse cardiovascular events and all-cause mortality. Diabetes Obes Metab. 2014;16(10):977-983. doi: 10.1111/dom.12306
53. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117-2128. doi: 10.1056/NEJMoa1504720
54. 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.2016;37(19):1526-1534. doi: 10.1093/eurheartj/ehv728
55. Scheen AJ. Reduction in cardiovascular and all-cause mortality in the EMPA-REG OUTCOME trial: A critical analysis. Diabetes Metab. 2016;42(2):71-76. doi: 10.1016/j.diabet.2015.12.005
Supplementary files
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1. Figure 1. Comparion of lethal risk in clinical investigation of several new antihypeglicemic drugs | |
Subject | Эффективность и безопасность антигипергликемической терапии | |
Type | Результаты исследования | |
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(69KB)
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Review
For citations:
Kakorin S.V., Iskandaryan R.A., Mkrtumyan A.M. Glycemia control and glucose-lowering therapy in patients with type 2 diabetes mellitus and cardiovascular disease (review of multicenter randomized trials). Diabetes mellitus. 2016;19(3):221-228. (In Russ.) https://doi.org/10.14341/DM2003422-27

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