Пиоглитазон – забытый сахароснижающий препарат с доказанными кардиопротективными и нефропротективными свойствами
Пиоглитазон – забытый сахароснижающий препарат с доказанными кардиопротективными и нефропротективными свойствами
Пешева Е.Д., Фадеев В.В. Пиоглитазон – забытый сахароснижающий препарат с доказанными кардиопротективными и нефропротективными свойствами. Consilium Medicum. 2021; 23 (4): 366–371.
DOI: 10.26442/20751753.2021.4.200892
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Pesheva ED, Fadeev VV. Pioglitazone is a forgotten hypoglycemic drug with proven cardioprotective and nephroprotective properties. Consilium Medicum. 2021; 23 (4): 366–371. DOI: 10.26442/20751753.2021.4.200892
Пиоглитазон – забытый сахароснижающий препарат с доказанными кардиопротективными и нефропротективными свойствами
Пешева Е.Д., Фадеев В.В. Пиоглитазон – забытый сахароснижающий препарат с доказанными кардиопротективными и нефропротективными свойствами. Consilium Medicum. 2021; 23 (4): 366–371.
DOI: 10.26442/20751753.2021.4.200892
________________________________________________
Pesheva ED, Fadeev VV. Pioglitazone is a forgotten hypoglycemic drug with proven cardioprotective and nephroprotective properties. Consilium Medicum. 2021; 23 (4): 366–371. DOI: 10.26442/20751753.2021.4.200892
Учитывая многокомпонентность сахарного диабета 2-го типа, а также его ассоциацию с крайне высоким риском макрососудистых осложнений (инфаркта миокарда, инсульта и смерти от сердечно-сосудистых заболеваний), в настоящее время большое внимание уделяется выбору сахароснижающих препаратов с учетом индивидуальных особенностей пациента. В первую очередь предпочтение отдается представителям классов, положительно влияющих на сердечно-сосудистые исходы. Помимо относительно новых молекул (ингибиторы натрий-глюкозного котранспортера 2-го типа и агонисты рецепторов глюкагоноподобного пептида-1) из поля зрения исследователей не уходит давно известный препарат пиоглитазон, входящий в группу тиазолидиндионов. Важно отметить, что кардиопротективный эффект пиоглитазона подтвержден в нескольких крупных рандомизированных исследованиях, в которых выявлены замедление атеросклеротического процесса и сокращение рисков сердечно-сосудистых заболеваний (PERISCOPE, Chicago, IRIS и PROactive). Являясь сенситайзером инсулина, пиоглитазон уменьшает инсулинорезистентность, оказывает протективный эффект на β-клетки поджелудочной железы, а также позитивно влияет на компоненты синдрома инсулинорезистентности (снижает уровень артериального давления, показателей липидного спектра) и улучшает течение неалкогольной жировой болезни печени. Наряду с указанным имеются данные о возможных побочных эффектах (увеличение массы тела, задержка жидкости, переломы), но их выраженность уменьшается при снижении дозы.
Ключевые слова: сахарный диабет 2-го типа, пиоглитазон, тиазолидиндионы, инсулинорезистентность, гипергликемия, сердечно-сосудистые заболевания
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Considering that type 2 diabetes mellitus is a multicomponent disease and is associated with an extremely high risk of macrovascular complications (myocardial infarction, stroke and death from cardiovascular diseases), at present, much attention is paid to the choice of hypoglycemic drugs, given the individual characteristics of the patient. Preference is given to drugs of those classes that have a positive effect on cardiovascular outcomes. Along with relatively new molecules (inhibitors of the sodium-glucose cotransporter type 2 and agonists of glucagon-like peptide-1 receptors), the well-known drug pioglitazone, which belongs to the thiazolidinediones group, has not left the field of attention of researchers. Importantly, the cardioprotective effect of pioglitazone has been confirmed in several large randomized trials that showed a delay in atherosclerosis and a reduced risk of cardiovascular disease (PERISCOPE, Chicago, IRIS and PROactive). As an insulin sensitizer, pioglitazone reduces insulin resistance, has a protective effect on pancreatic β-cells, and also has a beneficial effect on components of insulin resistance syndrome (lowers blood pressure, lipid spectrum parameters) and improves the course of non-alcoholic fatty liver disease. There is evidence of possible side effects (weight gain, fluid retention, fractures), but their severity decreases with decreasing dose of the drug.
1. Morrish NJ, Wang SL, Stevens LK, et al. Mortality and causes of death in the WHO multinational study of vascular disease in diabetes. Diabetologia. 2001;44:S14-S21.
2. Rawshani A, Rawshani A, Franzen S, et al. Mortality and cardiovascular disease in type 1 and type 2 diabetes. New Engl J Med. 2017;376:1407-18.
3. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837-53.
4. Gerstein HC, Miller ME, Byington RP, et al. Effects of intensive glucose lowering in type 2 diabetes. New Engl J Med. 2008;358:2545-59.
5. Phillips SA, Ciaraldi TP, Kong AP, et al. Modulation of circulating and adipose tissue adiponectin levels by antidiabetic therapy. Diabetes. 2003;52(3):667-74.
6. Yki-Jarvinen H. Thiazolidinediones. New Engl J Med. 2004;351:1106-18.
7. Belfort R, Harrison SA, Brown K, et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med. 2006;355(22):2297-307.
8. Choi D, Kim SK, Choi SH, et al. Preventative effects of rosiglitazone on restenosis after coronary stent implantation in patients with type 2 diabetes. Diabetes Care. 2004;27:2654-60.
9. Mazzone T, Meyer PM, Feinstein SB, et al. Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes:a randomized trial. JAMA. 2006;296:2572-81.
10. Kernan WN, Viscoli CM, Furie KL, et al. Pioglitazone after ischemic stroke or transient ischemic attack. New Engl Med. 2016;374:1321-31.
11. Sinha B, Ghosal S. Assessing the need for pioglitazone in the treatment of patients with type 2 diabetes:a meta-analysis of its risks and benefits from prospective trials. Sci Rep. 2020;10(1):15781.
12. De Jong M, Vander Worp HB, Vander Graaf Y, et al. Pioglitazone and the secondary prevention of cardiovascular disease. A meta-analysis of randomized-controlled trials. Cardiovasc Diabetol. 2017;16:134. DOI:10.1186/s12933-017-0617-4
13. Erdmann E, Harding S, Lam H, et al. Ten-year observational follow-up of PROactive:a randomized cardiovascular outcomes trial evaluating pioglitazone in type 2 diabetes. Diabetes Obes Metab. 2016;18:266-73.
14. Dormandy JA, Charbonnel B, Eckland DJ, 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 randomized controlled trial. Lancet. 2005;366:1279-89.
15. Liao HW, Saver JL, Wu YL, et al. Pioglitazone and cardiovascular outcomes in patients with insulin resistance, pre-diabetes and type 2 diabetes:a systematic review and meta-analysis. BMJ Open. 2017;7:e013927.
16. Yaghi S, Furie KL, Viscoli CM, et al. Pioglitazone prevents stroke in patients with a recent transient ischemic attack or ischemic stroke: a planned secondary analysis of the IRIS trial (insulin resistance intervention after stroke). Circulation. 2018;137:455-63. DOI:10.1161/CIRCULATIONAHA.117.030458
17. DeFronzo RA, Mehta RJ, Schnure JJ. Pleiotropic effects of thiazolidinediones:implications for the treatment of patients with type 2 diabetes mellitus. Hosp Pract. 2013;41:132-47.
18. Kumar J, Memon RS, Shahid I, et al. Antidiabetic drugs and non-alcoholic fatty liver disease: A systematic review, meta-analysis and evidence map. Dig Liver Dis. 2021;53(1):44-51.
19. Nesto R, Bell D, Bonow R, et al. Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. Diabetes Care. 2004;27(1):256-63. DOI:10.2337/diacare.27.1.256
20. Lago R, Singh P, Nesto R. Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones:a meta-analysis of randomised clinical trials. Lancet. 2007;370:1129-36.
21. Tang H, Shi W, Fu S, et al. Pioglitazone and bladder cancer risk:a systematic review and meta-analysis. Cancer Med. 2018;7(4):1070-80.
22. DeFronzo RA, Inzucchi S, Abdul-Ghani M, Nissen SE. Pioglitazone: the forgotten, cost-effective cardioprotective drug for type 2 diabetes. Diab Vasc Dis Res. 2019;16(2):133-43. DOI:10.1177/1479164118825376
23. Aghamohammadzadeh N, Niafar M, Dalir Abdolahinia E, et al. The effect of pioglitazone on weight, lipid profile and liver enzymes in type 2 diabetic patients. Ther Adv Endocrinol Metab. 2015;6(2):56-60. DOI:10.1177/2042018815574229
24. Schernthaner G, Currie CJ, Schernthaner GH. Do we still need pioglitazone for the treatment of type 2 diabetes? A risk-benefit critique in 2013. Diabetes Care. 2013 Aug;36 Suppl. 2(Suppl. 2):S155-61. DOI:10.2337/dcS13-2031
________________________________________________
1. Morrish NJ, Wang SL, Stevens LK, et al. Mortality and causes of death in the WHO multinational study of vascular disease in diabetes. Diabetologia. 2001;44:S14-S21.
2. Rawshani A, Rawshani A, Franzen S, et al. Mortality and cardiovascular disease in type 1 and type 2 diabetes. New Engl J Med. 2017;376:1407-18.
3. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837-53.
4. Gerstein HC, Miller ME, Byington RP, et al. Effects of intensive glucose lowering in type 2 diabetes. New Engl J Med. 2008;358:2545-59.
5. Phillips SA, Ciaraldi TP, Kong AP, et al. Modulation of circulating and adipose tissue adiponectin levels by antidiabetic therapy. Diabetes. 2003;52(3):667-74.
6. Yki-Jarvinen H. Thiazolidinediones. New Engl J Med. 2004;351:1106-18.
7. Belfort R, Harrison SA, Brown K, et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med. 2006;355(22):2297-307.
8. Choi D, Kim SK, Choi SH, et al. Preventative effects of rosiglitazone on restenosis after coronary stent implantation in patients with type 2 diabetes. Diabetes Care. 2004;27:2654-60.
9. Mazzone T, Meyer PM, Feinstein SB, et al. Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes:a randomized trial. JAMA. 2006;296:2572-81.
10. Kernan WN, Viscoli CM, Furie KL, et al. Pioglitazone after ischemic stroke or transient ischemic attack. New Engl Med. 2016;374:1321-31.
11. Sinha B, Ghosal S. Assessing the need for pioglitazone in the treatment of patients with type 2 diabetes:a meta-analysis of its risks and benefits from prospective trials. Sci Rep. 2020;10(1):15781.
12. De Jong M, Vander Worp HB, Vander Graaf Y, et al. Pioglitazone and the secondary prevention of cardiovascular disease. A meta-analysis of randomized-controlled trials. Cardiovasc Diabetol. 2017;16:134. DOI:10.1186/s12933-017-0617-4
13. Erdmann E, Harding S, Lam H, et al. Ten-year observational follow-up of PROactive:a randomized cardiovascular outcomes trial evaluating pioglitazone in type 2 diabetes. Diabetes Obes Metab. 2016;18:266-73.
14. Dormandy JA, Charbonnel B, Eckland DJ, 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 randomized controlled trial. Lancet. 2005;366:1279-89.
15. Liao HW, Saver JL, Wu YL, et al. Pioglitazone and cardiovascular outcomes in patients with insulin resistance, pre-diabetes and type 2 diabetes:a systematic review and meta-analysis. BMJ Open. 2017;7:e013927.
16. Yaghi S, Furie KL, Viscoli CM, et al. Pioglitazone prevents stroke in patients with a recent transient ischemic attack or ischemic stroke: a planned secondary analysis of the IRIS trial (insulin resistance intervention after stroke). Circulation. 2018;137:455-63. DOI:10.1161/CIRCULATIONAHA.117.030458
17. DeFronzo RA, Mehta RJ, Schnure JJ. Pleiotropic effects of thiazolidinediones:implications for the treatment of patients with type 2 diabetes mellitus. Hosp Pract. 2013;41:132-47.
18. Kumar J, Memon RS, Shahid I, et al. Antidiabetic drugs and non-alcoholic fatty liver disease: A systematic review, meta-analysis and evidence map. Dig Liver Dis. 2021;53(1):44-51.
19. Nesto R, Bell D, Bonow R, et al. Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. Diabetes Care. 2004;27(1):256-63. DOI:10.2337/diacare.27.1.256
20. Lago R, Singh P, Nesto R. Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones:a meta-analysis of randomised clinical trials. Lancet. 2007;370:1129-36.
21. Tang H, Shi W, Fu S, et al. Pioglitazone and bladder cancer risk:a systematic review and meta-analysis. Cancer Med. 2018;7(4):1070-80.
22. DeFronzo RA, Inzucchi S, Abdul-Ghani M, Nissen SE. Pioglitazone: the forgotten, cost-effective cardioprotective drug for type 2 diabetes. Diab Vasc Dis Res. 2019;16(2):133-43. DOI:10.1177/1479164118825376
23. Aghamohammadzadeh N, Niafar M, Dalir Abdolahinia E, et al. The effect of pioglitazone on weight, lipid profile and liver enzymes in type 2 diabetic patients. Ther Adv Endocrinol Metab. 2015;6(2):56-60. DOI:10.1177/2042018815574229
24. Schernthaner G, Currie CJ, Schernthaner GH. Do we still need pioglitazone for the treatment of type 2 diabetes? A risk-benefit critique in 2013. Diabetes Care. 2013 Aug;36 Suppl. 2(Suppl. 2):S155-61. DOI:10.2337/dcS13-2031
Авторы
Е.Д. Пешева, В.В. Фадеев*
ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия
*walfad@mail.ru
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Ekaterina D. Pesheva , Valentin V. Fadeev*
Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
*walfad@mail.ru