evrazkarЕвразийский Кардиологический ЖурналEurasian heart journal2225-16852305-0748Евразийская ассоциация кардиологов10.38109/2225-1685-2021-3-36-45evrazkar-6281Research ArticleОБЗОРЫREVIEWSИсследование ADVANCE 20 лет спустяADVANCE research 20 years laterhttps://orcid.org/0000-0003-1126-4282КобалаваЖ. Д.KobalavaZh. D.

Кобалава Жанна Давидовна, д.м.н., профессор, член-корр. РАН, зав. кафедрой внутренних болезней с курсом кардиологии и функциональной диагностики им. академика В.С. Моисеева, Городская клиническая больница им. В.В. Виноградова, Медицинский институт

Zhanna D. Kobalava, Dr. of Sci. (Med.), Professor, Correspondent Member of Russian Academy of Science, Head of Chair of Internal Medicine with the Subspecialty of Cardiology and Functional Diagnostics named after V.S. Moiseev, Institute of Medicine

Vavilova st., 61, Moscow 117292

https://orcid.org/0000-0001-7001-5855КолесникЭ. Л.KolesnikE. L.

Колесник Этери Ладовна, к.м.н., ассистент, кафедра внутренних болезней с курсом кардиологии и функциональной диагностики им. академика В.С. Моисеева, Городская клиническая больница им. В.В. Виноградова, Медицинский институт

Eteri L. Kolesnik, Cand. of Sci. (Med.), Assistant, Chair of Internal Medicine with the Subspecialty of Cardiology and Functional Diagnostics named after V.S. Moiseev, Institute of Medicine

Vavilova st., 61, Moscow 117292

eteri.kolesnik@gmail.comФГАОУ ВО Российский университет дружбы народовРоссияPeoples’ Friendship University of Russia (RUDN University)Russian Federation202125092021033645Copyright © Кобалава Ж.Д., Колесник Э.Л., 20212021Кобалава Ж.Д., Колесник Э.Л.Kobalava Z.D., Kolesnik E.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.heartj.asia/jour/article/view/6281

Наблюдательные и интервенционные исследования показали, что интенсивный контроль артериального давления может принести пользу пациентам с сахарным диабетом. Международное рандомизированное, контролируемое, клиническое исследование ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diarnicron MR Controlled Evaluation) стартовало в 2001 году. По результатам исследования риск основных микро- и макрососудистых событий (первичная конечная точка) достоверно снизился на 9%, при этом риски сердечно-сосудистой смерти и смерти от любой причины снизились, соответственно, на 18% и 14%. Было зарегистрировано снижение рисков микрососудистых осложнений – любого почечного события, появления или ухудшения нефропатии и появления микроальбуминурии на 21%, 18% и 21%, соответственно.

Результаты антигипертензивной части исследования ADVANCE дополнили расширяющуюся доказательную базу и послужили основой для изменения клинических рекомендаций по ведению пациентов с АГ и сахарным диабетом. Согласно обновленным объединенным рекомендациям Европейского общества кардиологов/Европейской ассоциации по изучению диабета (ESC/EASD) целевые уровни систолического/диастолического артериального давления должны составлять 130/80 мм рт.ст., с некоторыми исключениями, а фиксированная комбинация блокатора РААС с диуретиком или антагонистом кальция предлагается в качестве терапии первой линии.

По результатам наблюдательного исследования ADVANCE-ON, в котором приняли участие 8494 пациента из 11 140 пациентов, рандомизированных в исследование ADVANCE, был обнаружен эффект памяти, или «наследования», при котором интенсивный контроль артериального давления в ходе исследования оказывал благоприятное влияние на различные исходы после его прекращения. Эти данные подчеркивают важность достижения и сохранения оптимального контроля артериального давления для снижения риска микро- и макрососудистых осложнений.

Observational and interventional studies have shown that intensive blood pressure control may benefit in patients with diabetes. The Action in Diabetes and Vascular Disease: Preterax and Diarnicron MR Controlled Evaluation (ADVANCE) international randomized, controlled, clinical trial was launched in 2001. According to the results of the study, the risk of major micro- and macrovascular events (primary endpoint) significantly decreased by 9%, while the risks of cardiovascular death and death from any cause decreased by 18% and 14%, respectively. There was a decrease in the risks of microvascular complications – any renal event, the appearance or worsening of nephropathy and the appearance of microalbuminuria by 21%, 18% and 21%, respectively. The results of the antihypertensive part of the ADVANCE study supplemented the expanding evidence base and served as the basis for changing clinical guidelines for the management of patients with hypertension and diabetes. According to the updated joint guidelines of the European Society of 

Cardiology / European Association for the Study of Diabetes (ESC/EASD), the target systolic / diastolic blood pressure levels should be 130/80 mmHg, with some exceptions, and the fixed combination of the RAAS blocker with a diuretic or calcium antagonist is suggested as first-line therapy.

The observational ADVANCE-ON study, which enrolled 8494 patients out of 11 140 patients randomized to the ADVANCE study, found a memory effect, or ‘inheritance’, in which intensive blood pressure control during the study had a beneficial effect on various outcomes after its termination. These findings highlight the importance of achieving and maintaining optimal blood pressure control to reduce the risk of micro- and macrovascular complications.

артериальная гипертониясахарный диабет 2 типакомбинированная антигипертензивная терапияинтенсивный контроль артериального давления (АД)интенсивный контроль гликемииarterial hypertensiontype 2 diabetescombined antihypertensive therapyintensive blood pressure (BP) controlintensive glycemic controlReferencesGBD 2019 Risk Factors Collaborators. Global burden of 87 risk factors in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1223–49.GBD 2019 Risk Factors Collaborators. Global burden of 87 risk factors in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1223–49.Williams B., Mancia G., Spiering W. et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021–104.Williams B., Mancia G., Spiering W. et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021–104.Муромцева Г.А., Концевая А.В., Константинов В.В. и др. Распространенность факторов риска неинфекционных заболеваний в российской популяции в 2012-2013 гг. Результаты исследования ЭССЕ-РФ. Кардиоваскулярная терапия и профилактика. 2014;13(6):4–11.Muromtseva G.A., Kontsevaya A.V., Konstantinov V.V. et al. Prevalence of risk factors for infectious diseases in the Russian population in 2012-2013. ESSE-RF research results. Cardiovascular therapy and prevention. 2014; 13 (6): 4-11(in Russ.)Gu Q., Burt V.L., Dillon C.F., Yoon S. Trends in Antihypertensive Medication Use and Blood Pressure Control Among United States Adults With Hypertension. Circulation. 2012;126(17):2105–14.Gu Q., Burt V.L., Dillon C.F., Yoon S. Trends in Antihypertensive Medication Use and Blood Pressure Control Among United States Adults With Hypertension. Circulation. 2012;126(17):2105–14.IDF Diabetes Atlas 9th edition 2019. https://www.diabetesatlas.org/en/ (31 May 2021).IDF Diabetes Atlas 9th edition 2019. https://www.diabetesatlas.org/en/ (31 May 2021).Дедов И.И., Шестакова М.В., Галстян Г.Р. Распространенность сахарного диабета 2 типа у взрослого населения России (исследование NATION). Сахарный диабет. 2016;19(2):104–12.Dedov I.I., Shestakova M.V., Galstyan G.R. Prevalence of type 2 diabetes mellitus in the adult population of Russia (NATION study). Diabetes. 2016; 19 (2): 104–12 (in Russ.).Кобалава Ж.Д., Котовская Ю.В., Моисеев В.С. Артериальная гипертония. Ключи к диагностике и лечению: Серия «Библиотека врачаспециалиста». Москва: ГЭОТАР-Медиа; 2009. 864 p.Kobalava Zh.D., Kotovskaya Yu.V., Moiseev V.S. Arterial hypertension. Keys to Diagnosis and Treatment: The Medical Specialist Library Series. Moscow: GEOTARMedia; 2009.864 p. (in Russ).Чазова И.Е., Шестакова М.В., Жернакова Ю.В. и др. Рекомендации по ведению больных артериальной гипертонией с метаболическими нарушениями и сахарным диабетом 2-го типа. Системные Гипертензии. 2020;17(1).Chazova I.E., Shestakova M.V., Zhernakova Yu.V et al. Recommendations for the management of patients with arterial hypertension with metabolic disorders and type 2 diabetes mellitus. Systemic Hypertension [Internet]. 2020; 17 (1). (in Russ).Kocemba J., Kawecka-Jaszcz K., Gryglewska B., Grodzicki T. Isolated systolic hypertension: pathophysiology, consequences and therapeutic benefits. J Hum Hypertens. 1998;12(9):621–6.Kocemba J., Kawecka-Jaszcz K., Gryglewska B., Grodzicki T. Isolated systolic hypertension: pathophysiology, consequences and therapeutic benefits. J Hum Hypertens. 1998;12(9):621–6.Alsuwaida A., Parkes R., So J. et al. High prevalence of masked hypertension in treated hypertensive patients with type 2 diabetes mellitus. Saudi J Kidney Dis Transpl. 2006;17(3):326–37.Alsuwaida A., Parkes R., So J. et al. High prevalence of masked hypertension in treated hypertensive patients with type 2 diabetes mellitus. Saudi J Kidney Dis Transpl. 2006;17(3):326–37.Cuspidi C., Meani S., Lonati L. et al. Short-term reproducibility of a non-dipping pattern in type 2 diabetic hypertensive patients. J Hypertens. 2006;24(4):647–53.Cuspidi C., Meani S., Lonati L. et al. Short-term reproducibility of a non-dipping pattern in type 2 diabetic hypertensive patients. J Hypertens. 2006;24(4):647–53.Sowers J.R., Haffner S. Treatment of cardiovascular and renal risk factors in the diabetic hypertensive. Hypertension. 2002;40(6):781–8.Sowers J.R., Haffner S. Treatment of cardiovascular and renal risk factors in the diabetic hypertensive. Hypertension. 2002;40(6):781–8.Kuriyama S., Otsuka Y., Iida R. et al. Morning blood pressure predicts hypertensive organ damage in patients with renal diseases: effect of intensive antihypertensive therapy in patients with diabetic nephropathy. Intern Med. 2005;44(12):1239–46.Kuriyama S., Otsuka Y., Iida R. et al. Morning blood pressure predicts hypertensive organ damage in patients with renal diseases: effect of intensive antihypertensive therapy in patients with diabetic nephropathy. Intern Med. 2005;44(12):1239–46.Lewington S., Clarke R., Qizilbash N. et al. Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360(9349):1903–13.Lewington S., Clarke R., Qizilbash N. et al. Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360(9349):1903–13.Stamler J., Vaccaro O., Neaton JD., Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care. 1993;16(2):434–44.Stamler J., Vaccaro O., Neaton JD., Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care. 1993;16(2):434–44.Дзяк Г.В., Колесник Т.В., Погорецкий Ю.Н. Суточное мониторирование артериального давления. Днепропетровск: Пороги; 2005. 200 c.Dzyak G.V., Kolesnik T.V., Pogoretsky Yu.N. Daily monitoring of blood pressure. Dnepropetrovsk: Rapids; 2005.200 p. (in Russ).Group BMJP. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998;317(7160):703–13.Group BMJP. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998;317(7160):703–13.Hansson L., Zanchetti A., Carruthers S.G., et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet. 1998;351(9118):1755–62.Hansson L., Zanchetti A., Carruthers S.G., et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet. 1998;351(9118):1755–62.Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. Lancet. 2000;355(9200):253–9.Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. Lancet. 2000;355(9200):253–9.The EUCLID Study Group. Randomised placebo-controlled trial of lisinopril in normotensive patients with insulin-dependent diabetes and normoalbuminuria or microalbuminuria. Lancet. 1997;349(9068):1787–92.The EUCLID Study Group. Randomised placebo-controlled trial of lisinopril in normotensive patients with insulin-dependent diabetes and normoalbuminuria or microalbuminuria. Lancet. 1997;349(9068):1787–92.Chan J.C., Ko G.T., Leung D.H. et al. Long-term effects of angiotensinconverting enzyme inhibition and metabolic control in hypertensive type 2 diabetic patients. Kidney Int. 2000;57(2):590–600.Chan J.C., Ko G.T., Leung D.H. et al. Long-term effects of angiotensinconverting enzyme inhibition and metabolic control in hypertensive type 2 diabetic patients. Kidney Int. 2000;57(2):590–600.Estacio R.O., Jeffers B.W., Gifford N., Schrier RW. Effect of blood pressure control on diabetic microvascular complications in patients with hypertension and type 2 diabetes. Diabetes Care. 2000;23 Suppl 2:B54-64.Estacio R.O., Jeffers B.W., Gifford N., Schrier RW. Effect of blood pressure control on diabetic microvascular complications in patients with hypertension and type 2 diabetes. Diabetes Care. 2000;23 Suppl 2:B54-64.Brenner B.M., Cooper M.E., de Zeeuw D. et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861–9.Brenner B.M., Cooper M.E., de Zeeuw D. et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861–9.Lewis E.J., Hunsicker L.G., Clarke W.R. et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345(12):851–60.Lewis E.J., Hunsicker L.G., Clarke W.R. et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345(12):851–60.Parving H.H., Lehnert H., Bröchner-Mortensen J. et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001;345(12):870–8.Parving H.H., Lehnert H., Bröchner-Mortensen J. et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001;345(12):870–8.Strippoli G.F.M, Craig M., Deeks JJ., et al. Effects of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists on mortality and renal outcomes in diabetic nephropathy: systematic review. BMJ. 2004;329(7470):828.Strippoli G.F.M, Craig M., Deeks JJ., et al. Effects of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists on mortality and renal outcomes in diabetic nephropathy: systematic review. BMJ. 2004;329(7470):828.ADVANCE Management Committee. Study rationale and design of ADVANCE: action in diabetes and vascular disease--preterax and diamicron MR controlled evaluation. Diabetologia. 2001 Sep;44(9):1118–20.ADVANCE Management Committee. Study rationale and design of ADVANCE: action in diabetes and vascular disease--preterax and diamicron MR controlled evaluation. Diabetologia. 2001 Sep;44(9):1118–20.Dahlöf B., Gosse P., Guéret P., et al. Perindopril/indapamide combination more effective than enalapril in reducing blood pressure and left ventricular mass: the PICXEL study. J Hypertens. 2005; 23 (11): 2063-2070.Dahlöf B., Gosse P., Guéret P., et al. Perindopril/indapamide combination more effective than enalapril in reducing blood pressure and left ventricular mass: the PICXEL study. J Hypertens. 2005; 23 (11): 2063-2070.PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet. 2001;358(9287):1033–41.PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet. 2001;358(9287):1033–41.Effects of PREMIER Lifestyle Modifications on Participants With and Without the Metabolic Syndrome Hypertension https://www.ahajournals.org/doi/full/10.1161/hypertensionaha.107.089458 (5 Aug 2021).Effects of PREMIER Lifestyle Modifications on Participants With and Without the Metabolic Syndrome Hypertension https://www.ahajournals.org/doi/full/10.1161/hypertensionaha.107.089458 (5 Aug 2021).Fox KM, EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet. 2003;362(9386):782–8.Fox KM, EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet. 2003;362(9386):782–8.Meurin P. The ASCOT trial: clarifying the role of ACE inhibition in the reduction of cardiovascular events in patients with hypertension. Am J Cardiovasc Drugs. 2006;6(5):327–34.Meurin P. The ASCOT trial: clarifying the role of ACE inhibition in the reduction of cardiovascular events in patients with hypertension. Am J Cardiovasc Drugs. 2006;6(5):327–34.Patel A., ADVANCE Collaborative Group, MacMahon S, Chalmers J, Neal B, Woodward M, et al. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet. 2007;370(9590):829–40.Patel A., ADVANCE Collaborative Group, MacMahon S, Chalmers J, Neal B, Woodward M, et al. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet. 2007;370(9590):829–40.Estacio R.O., Jeffers B.W., Hiatt W.R., et al. The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension. N Engl J Med. 1998;338(10):645–52.Estacio R.O., Jeffers B.W., Hiatt W.R., et al. The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension. N Engl J Med. 1998;338(10):645–52.Schrier R.W., Estacio R.O., Esler A., Mehler P. Effects of aggressive blood pressure control in normotensive type 2 diabetic patients on albuminuria, retinopathy and strokes. Kidney Int. 2002;61(3):1086–97.Schrier R.W., Estacio R.O., Esler A., Mehler P. Effects of aggressive blood pressure control in normotensive type 2 diabetic patients on albuminuria, retinopathy and strokes. Kidney Int. 2002;61(3):1086–97.Cosentino F, Grant PJ, Aboyans V, Bailey CJ. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2019;41(2):255–323.Cosentino F, Grant PJ, Aboyans V, Bailey CJ. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2019;41(2):255–323.Dluhy R.G., McMahon G.T. Intensive glycemic control in the ACCORD and ADVANCE trials. N Engl J Med. 2008;358(24):2630–3.Dluhy R.G., McMahon G.T. Intensive glycemic control in the ACCORD and ADVANCE trials. N Engl J Med. 2008;358(24):2630–3.ACCORD Study Group, Buse J.B., Bigger J.T., et al. Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods. Am J Cardiol. 2007;99(12A):21i–33i.ACCORD Study Group, Buse J.B., Bigger J.T., et al. Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods. Am J Cardiol. 2007;99(12A):21i–33i.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. 2008;358(24):2560–72.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. 2008;358(24):2560–72.Duckworth W., Abraira C., Moritz T., et al. Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes. N Engl J Med. 2009;360(2):129–39.Duckworth W., Abraira C., Moritz T., et al. Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes. N Engl J Med. 2009;360(2):129–39.Schernthaner G., Grimaldi A., Di Mario U., et al. GUIDE study: double-blind comparison of once-daily gliclazide MR and glimepiride in type 2 diabetic patients. Eur J Clin Invest. 2004;34(8):535–42.Schernthaner G., Grimaldi A., Di Mario U., et al. GUIDE study: double-blind comparison of once-daily gliclazide MR and glimepiride in type 2 diabetic patients. Eur J Clin Invest. 2004;34(8):535–42.Zoungas S., Chalmers J., Kengne AP., et al. The efficacy of lowering glycated haemoglobin with a gliclazide modified release-based intensive glucose lowering regimen in the ADVANCE trial. Diabetes Res Clin Pract. 2010;89(2):126–33.Zoungas S., Chalmers J., Kengne AP., et al. The efficacy of lowering glycated haemoglobin with a gliclazide modified release-based intensive glucose lowering regimen in the ADVANCE trial. Diabetes Res Clin Pract. 2010;89(2):126–33.Woodward M., Patel A., Zoungas S. et al. Does glycemic control offer similar benefits among patients with diabetes in different regions of the world? Results from the ADVANCE trial. Diabetes Care. 2011;34(12):2491–5.Woodward M., Patel A., Zoungas S. et al. Does glycemic control offer similar benefits among patients with diabetes in different regions of the world? Results from the ADVANCE trial. Diabetes Care. 2011;34(12):2491–5.Van Dieren S., Kengne A.P., Chalmers J., et al. Intensification of medication and glycaemic control among patients with type 2 diabetes - the ADVANCE trial. Diabetes Obes Metab. 2014;16(5):426–32.Van Dieren S., Kengne A.P., Chalmers J., et al. Intensification of medication and glycaemic control among patients with type 2 diabetes - the ADVANCE trial. Diabetes Obes Metab. 2014;16(5):426–32.Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein H.C., Miller M.E., et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358(24):2545–59.Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein H.C., Miller M.E., et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358(24):2545–59.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(9131):837–53.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(9131):837–53.UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352(9131):854–65.UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352(9131):854–65.Control Group, Turnbull F.M., Abraira C., Anderson R.J., et al. Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia. 2009;52(11):2288–98.Control Group, Turnbull F.M., Abraira C., Anderson R.J., et al. Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia. 2009;52(11):2288–98.Zoungas S., Arima H., Gerstein H.C., et al. Effects of intensive glucose control on microvascular outcomes in patients with type 2 diabetes: a meta-analysis of individual participant data from randomised controlled trials. Lancet Diabetes Endocrinol. 2017;5(6):431–7.Zoungas S., Arima H., Gerstein H.C., et al. Effects of intensive glucose control on microvascular outcomes in patients with type 2 diabetes: a meta-analysis of individual participant data from randomised controlled trials. Lancet Diabetes Endocrinol. 2017;5(6):431–7.Nathan D.M., Cleary P.A., Backlund J.-Y.C., et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;353(25):2643–53.Nathan D.M., Cleary P.A., Backlund J.-Y.C., et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;353(25):2643–53.Holman R.R., Paul S.K., Bethel M.A. et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359(15):1577–89.Holman R.R., Paul S.K., Bethel M.A. et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359(15):1577–89.Holman R.R., Paul S.K., Bethel M.A. et al. Long-term follow-up after tight control of blood pressure in type 2 diabetes. N Engl J Med. 2008;359(15):1565–76.Holman R.R., Paul S.K., Bethel M.A. et al. Long-term follow-up after tight control of blood pressure in type 2 diabetes. N Engl J Med. 2008;359(15):1565–76.Zoungas S., Chalmers J., Neal B., Billot L., Li Q., Hirakawa Y., et al. Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. N Engl J Med. 2014;371(15):1392–406.Zoungas S., Chalmers J., Neal B., Billot L., Li Q., Hirakawa Y., et al. Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. N Engl J Med. 2014;371(15):1392–406.Blood Pressure Lowering Treatment Trialists’ Collaboration. Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure: an individual participant-level data meta-analysis. Lancet. 2021;397(10285):1625–36.Blood Pressure Lowering Treatment Trialists’ Collaboration. Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure: an individual participant-level data meta-analysis. Lancet. 2021;397(10285):1625–36.

The authors declare that there are no conflicts of interest present.