SGLT2抑制剂对心力衰竭的影响
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摘要
糖尿病患者更易发生心力衰竭,伴随糖尿病的心力衰竭患者预后更差。目前已有的多种降糖药物对合并糖尿病的心衰患者治疗效果欠佳,有的甚至有害。SGLT2抑制剂是一种新型降糖药,在多项临床研究中发现其对心血管有保护作用。本文就SGLT2抑制剂对心力衰竭的影响做一综述。
A large number of studies have found that patients with diabetes are more likely to have heart failure, heart failure patients with diabetes usually have poorer prognosis, so that heart failure is a very important health problem in elderly diabetics in China. Currently, many kinds of hypoglycemic drugs on the market have poor therapeutic effect on heart failure patients with diabetes, some drugs are even harmful. Cardiovascular protective effect of SGLT2 inhibitors was observed in several clinical studies. In this paper, we are going to summarize the effect of SGLT2 inhibitors on heart failure.
A large number of studies have found that patients with diabetes are more likely to have heart failure, heart failure patients with diabetes usually have poorer prognosis, so that heart failure is a very important health problem in elderly diabetics in China. Currently, many kinds of hypoglycemic drugs on the market have poor therapeutic effect on heart failure patients with diabetes, some drugs are even harmful. Cardiovascular protective effect of SGLT2 inhibitors was observed in several clinical studies. In this paper, we are going to summarize the effect of SGLT2 inhibitors on heart failure.
引文
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[3] Aguilar D,Deswal A,Ramasubbu K,et al.Comparison of patients with heart failure and preserved left ventricular ejection fraction among those with versus without diabetes mellitus[J].Am J Cardiol, 2010, 105(3):373-377.
[4] 纪立农,郭立新,郭晓蕙,等.钠-葡萄糖共转运蛋白2(SGLT2)抑制剂临床合理应用中国专家建议[J].糖尿病天地(临床), 2016,24(12):865-870.
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[8] H?ring HU,Merker L,Seewaldtbecker E,et al.Empagliflozin as Add-On to Metformin in Patients With Type 2 Diabetes:A 24-Week, Randomized, Double-Blind, Placebo-Controlled Trial[J].Diabetes Care,2014,37(6):1650-1659.
[9] Nauck MA.Update on developments with SGLT2 inhibitors in the management of type 2 diabetes[J].Drug Des Devel Ther,2014(8):1335-1380. doi:10.2147/DDDT.S50773.
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[11] Li D,Shi W,Wang T, et al.SGLT2 inhibitor plus DPP-4 inhibitor as combination therapy for type 2 diabetes:A systematic review and meta-analysis[J].Diabetes Obes Metab,2018.doi:10.1111/dom.13294.
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[13] Dassanayaka S,Jones SP.O-GlcNAc and the cardiovascular system[J].Pharmacol Ther, 2014,142(1):62-71.
[14] Kota SK,Kota SK,Jammula S,et al.Effect of diabetes on alteration of metabolism in cardiac myocytes: therapeutic implications[J].Diabetes Technol Ther, 2011, 13(11):1155-1160.
[15] Boudina S,Abel ED.Mitochondrial uncoupling: a key contributor to reduced cardiac efficiency in diabetes[J].Physiology (Bethesda), 2006, 21(4):250-258.
[16] Bhimaraj A,Tang WH.Role of oxidative stress in disease progression in Stage B, a pre-cursor of heart failure[J].Heart Fail Clin, 2012, 8(1):101-111.
[17] Nishimura R,Tanaka Y,Koiwai K,et al.Effect of empagliflozin monotherapy on postprandial glucose and 24-hour glucose variability in Japanese patients with type 2 diabetes mellitus:a randomized,double-blind,placebo-controlled,4-week study[J].Cardiovasc Diabetol,2015,14(1):11.doi:10.1186/s12933-014-0169-9.
[18] Panchapakesan U,Pegg K,Gross S,et al.Effects of SGLT2 inhibition in human kidney proximal tubular cells--renoprotection in diabetic nephropathy?[J].PLoS One, 2013, 8(2):e54442.
[19] 刘治全. 心力衰竭治疗的基石:利尿剂[J].中华心血管病杂志, 2002, 30(5):319-320.
[20] Cherney DZ,Perkins BA,Soleymanlou N,et al. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus[J].Circulation,2014,129(5):587-597.
[21] Patil VC,Patil HV,Shah KB,et al.Diastolic dysfunction in asymptomatic type 2 diabetes mellitus with normal systolic function[J].J Cardiovasc Dis Res, 2011, 2(4):213-222.
[22] Seferovic PM,Paulus WJ.Clinical diabetic cardiomyopathy:a two-faced disease with restrictive and dilated phenotypes[J].Eur Heart J, 2015, 36(27):1718-1727, 1727a-1727c.
[23] Levelt E,Mahmod M,Piechnik SK,et al. Relationship Between Left Ventricular Structural and Metabolic Remodeling in Type 2 Diabetes[J].Diabetes, 2016, 65(1):44-52.
[24] 侯亚利, 刘永铭, 马苏美, 等.2型糖尿病患者心脏功能变化的研究[J].中国糖尿病杂志, 2011, 19(11):834-837.
[25] Tervaert TW,Mooyaart AL,Amann K,et al.Pathologic classification of diabetic nephropathy[J].J Am Soc Nephrol, 2010, 21(4):556-563.
[26] Barnett AH,Mithal A,Manassie J, et al.Efficacy and safety of empagliflozin added to existing antidiabetes treatment in patients with type 2 diabetes and chronic kidney disease: a randomised, double-blind, placebo-controlled trial[J].Lancet Diabetes Endocrinol, 2014, 2(5):369-384.
[27] Kojima N,Williams JM,Takahashi T,et al.Effects of a new SGLT2 inhibitor, luseogliflozin,on diabetic nephropathy in T2DN rats[J].J Pharmacol Exp Ther, 2013, 345(3):464-472.
[28] Mazidi M,Rezaie P,Gao HK,et al.Effect of Sodium-Glucose Cotransport-2 Inhibitors on Blood Pressure in People With Type 2 Diabetes Mellitus:A Systematic Review and Meta-Analysis of 43 Randomized Control Trials With 22 528 Patients[J].J Am Heart Assoc, 2017, 6(6):e004007.
[29] Imprialos KP,Sarafidis PA,Karagianni AI.Sodium-glucose cotransporter-2 inhibitors and blood pressure decrease:a valuable effect of a novel antidiabetic class[J].J Hypertens, 2015,33(11):2185-2197.
[30] Cherney DZ,Perkins BA,Soleymanlou N,et al.The effect of empagliflozin on arterial stiffness and heart rate variability in subjects with uncomplicated type 1 diabetes mellitus[J].Cardiovasc Diabetol, 2014, 13(1):28.
[31] Prasad M,Matteson EL,Herrmann J,et al.Uric Acid Is Associated With Inflammation, Coronary Microvascular Dysfunction,and Adverse Outcomes in Postmenopausal Women[J]. Hypertension, 2017, 69(2):236-242.
[32] Tanaka T,Milaneschi Y,Zhang Y,et al.A double blind placebo controlled randomized trial of the effect of acute uric acid changes on inflammatory markers in humans:A pilot study[J].PLoS One, 2017, 12(8):e0181100.
[33] Mehta T,Nuccio E,McFann K,et al.Association of Uric Acid With Vascular Stiffness in the Framingham Heart Study[J].Am J Hypertens, 2015, 28(7):877-883.
[34] Huang H,Huang B,Li Y,et al.Uric acid and risk of heart failure: a systematic review and meta-analysis[J].Eur J Heart Fail,2014, 16(1):15-24.
[35] Cheeseman C.Solute carrier family 2,member 9 and uric acid homeostasis[J].Curr Opin Nephrol Hypertens,2009,18(5):428-432.
[36] Alon D,Stein GY,Korenfeld R,et al.Predictors and outcomes of infection-related hospital admissions of heart failure patients[J].PLoS One, 2013, 8(8):e72476.
[37] Taylor SI,Blau JE,Rother KI.Possible adverse effects of SGLT2 inhibitors on bone[J].Lancet Diabetes Endocrinol, 2015, 3(1):8-10.
[38] 吴宪,张冬颖,覃数.心力衰竭与骨质疏松相关性研究[J].临床医药文献电子杂志, 2017, 4(18):3550-3551.
[39] D'Elia JA,Segal AR,Bayliss GP,et al.Sodium-glucose cotransporter-2 inhibition and acidosis in patients with type 2 diabetes:a review of US FDA data and possible conclusions[J].Int J Nephrol Renovasc Dis,2017,(10):153-158. doi:10.2147/IJNRD.S135899.
[40] Taylor SI,Blau JE,Rother KI.SGLT2 Inhibitors May Predispose to Ketoacidosis[J].J Clin Endocrinol Metab, 2015, 100(8):2849-2852.
[2] Boonman-de Winter LJ,Rutten FH,Cramer MJ,et al.High prevalence of previously unknown heart failure and left ventricular dysfunction in patients with type 2 diabetes[J].Diabetologia,2012, 55(8):2154-2162.
[3] Aguilar D,Deswal A,Ramasubbu K,et al.Comparison of patients with heart failure and preserved left ventricular ejection fraction among those with versus without diabetes mellitus[J].Am J Cardiol, 2010, 105(3):373-377.
[4] 纪立农,郭立新,郭晓蕙,等.钠-葡萄糖共转运蛋白2(SGLT2)抑制剂临床合理应用中国专家建议[J].糖尿病天地(临床), 2016,24(12):865-870.
[5] Zinman B,Wanner C,Lachin JM,et al.Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes[J].N Engl J Med, 2015, 373(22):2117-2128.
[6] Joubert M,Jagu B,Montaigne D,et al.The Sodium-Glucose Cotransporter 2 Inhibitor Dapagliflozin Prevents Cardiomyopathy in a Diabetic Lipodystrophic Mouse Model[J].Diabetes, 2017, 66(4):1030-1040.
[7] Powell J,Miller SA,Taylor JR.Sodium-glucose cotransporter 2 inhibitors:the new option for diabetes mellitus management[J].South Med J, 2015, 108(2):82-90.
[8] H?ring HU,Merker L,Seewaldtbecker E,et al.Empagliflozin as Add-On to Metformin in Patients With Type 2 Diabetes:A 24-Week, Randomized, Double-Blind, Placebo-Controlled Trial[J].Diabetes Care,2014,37(6):1650-1659.
[9] Nauck MA.Update on developments with SGLT2 inhibitors in the management of type 2 diabetes[J].Drug Des Devel Ther,2014(8):1335-1380. doi:10.2147/DDDT.S50773.
[10] Kosiborod M,Gause-Nilsson I,Xu J,et al.Efficacy and safety of dapagliflozin in patients with type 2 diabetes and concomitant heart failure[J].J Diabetes Complications,2017,31(7):1215-1221.
[11] Li D,Shi W,Wang T, et al.SGLT2 inhibitor plus DPP-4 inhibitor as combination therapy for type 2 diabetes:A systematic review and meta-analysis[J].Diabetes Obes Metab,2018.doi:10.1111/dom.13294.
[12] Merovci A,Mari A,Solis C,et al.Dapagliflozin lowers plasma glucose concentration and improves beta-cell function[J].J Clin Endocrinol Metab, 2015, 100(5):1927-1932.
[13] Dassanayaka S,Jones SP.O-GlcNAc and the cardiovascular system[J].Pharmacol Ther, 2014,142(1):62-71.
[14] Kota SK,Kota SK,Jammula S,et al.Effect of diabetes on alteration of metabolism in cardiac myocytes: therapeutic implications[J].Diabetes Technol Ther, 2011, 13(11):1155-1160.
[15] Boudina S,Abel ED.Mitochondrial uncoupling: a key contributor to reduced cardiac efficiency in diabetes[J].Physiology (Bethesda), 2006, 21(4):250-258.
[16] Bhimaraj A,Tang WH.Role of oxidative stress in disease progression in Stage B, a pre-cursor of heart failure[J].Heart Fail Clin, 2012, 8(1):101-111.
[17] Nishimura R,Tanaka Y,Koiwai K,et al.Effect of empagliflozin monotherapy on postprandial glucose and 24-hour glucose variability in Japanese patients with type 2 diabetes mellitus:a randomized,double-blind,placebo-controlled,4-week study[J].Cardiovasc Diabetol,2015,14(1):11.doi:10.1186/s12933-014-0169-9.
[18] Panchapakesan U,Pegg K,Gross S,et al.Effects of SGLT2 inhibition in human kidney proximal tubular cells--renoprotection in diabetic nephropathy?[J].PLoS One, 2013, 8(2):e54442.
[19] 刘治全. 心力衰竭治疗的基石:利尿剂[J].中华心血管病杂志, 2002, 30(5):319-320.
[20] Cherney DZ,Perkins BA,Soleymanlou N,et al. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus[J].Circulation,2014,129(5):587-597.
[21] Patil VC,Patil HV,Shah KB,et al.Diastolic dysfunction in asymptomatic type 2 diabetes mellitus with normal systolic function[J].J Cardiovasc Dis Res, 2011, 2(4):213-222.
[22] Seferovic PM,Paulus WJ.Clinical diabetic cardiomyopathy:a two-faced disease with restrictive and dilated phenotypes[J].Eur Heart J, 2015, 36(27):1718-1727, 1727a-1727c.
[23] Levelt E,Mahmod M,Piechnik SK,et al. Relationship Between Left Ventricular Structural and Metabolic Remodeling in Type 2 Diabetes[J].Diabetes, 2016, 65(1):44-52.
[24] 侯亚利, 刘永铭, 马苏美, 等.2型糖尿病患者心脏功能变化的研究[J].中国糖尿病杂志, 2011, 19(11):834-837.
[25] Tervaert TW,Mooyaart AL,Amann K,et al.Pathologic classification of diabetic nephropathy[J].J Am Soc Nephrol, 2010, 21(4):556-563.
[26] Barnett AH,Mithal A,Manassie J, et al.Efficacy and safety of empagliflozin added to existing antidiabetes treatment in patients with type 2 diabetes and chronic kidney disease: a randomised, double-blind, placebo-controlled trial[J].Lancet Diabetes Endocrinol, 2014, 2(5):369-384.
[27] Kojima N,Williams JM,Takahashi T,et al.Effects of a new SGLT2 inhibitor, luseogliflozin,on diabetic nephropathy in T2DN rats[J].J Pharmacol Exp Ther, 2013, 345(3):464-472.
[28] Mazidi M,Rezaie P,Gao HK,et al.Effect of Sodium-Glucose Cotransport-2 Inhibitors on Blood Pressure in People With Type 2 Diabetes Mellitus:A Systematic Review and Meta-Analysis of 43 Randomized Control Trials With 22 528 Patients[J].J Am Heart Assoc, 2017, 6(6):e004007.
[29] Imprialos KP,Sarafidis PA,Karagianni AI.Sodium-glucose cotransporter-2 inhibitors and blood pressure decrease:a valuable effect of a novel antidiabetic class[J].J Hypertens, 2015,33(11):2185-2197.
[30] Cherney DZ,Perkins BA,Soleymanlou N,et al.The effect of empagliflozin on arterial stiffness and heart rate variability in subjects with uncomplicated type 1 diabetes mellitus[J].Cardiovasc Diabetol, 2014, 13(1):28.
[31] Prasad M,Matteson EL,Herrmann J,et al.Uric Acid Is Associated With Inflammation, Coronary Microvascular Dysfunction,and Adverse Outcomes in Postmenopausal Women[J]. Hypertension, 2017, 69(2):236-242.
[32] Tanaka T,Milaneschi Y,Zhang Y,et al.A double blind placebo controlled randomized trial of the effect of acute uric acid changes on inflammatory markers in humans:A pilot study[J].PLoS One, 2017, 12(8):e0181100.
[33] Mehta T,Nuccio E,McFann K,et al.Association of Uric Acid With Vascular Stiffness in the Framingham Heart Study[J].Am J Hypertens, 2015, 28(7):877-883.
[34] Huang H,Huang B,Li Y,et al.Uric acid and risk of heart failure: a systematic review and meta-analysis[J].Eur J Heart Fail,2014, 16(1):15-24.
[35] Cheeseman C.Solute carrier family 2,member 9 and uric acid homeostasis[J].Curr Opin Nephrol Hypertens,2009,18(5):428-432.
[36] Alon D,Stein GY,Korenfeld R,et al.Predictors and outcomes of infection-related hospital admissions of heart failure patients[J].PLoS One, 2013, 8(8):e72476.
[37] Taylor SI,Blau JE,Rother KI.Possible adverse effects of SGLT2 inhibitors on bone[J].Lancet Diabetes Endocrinol, 2015, 3(1):8-10.
[38] 吴宪,张冬颖,覃数.心力衰竭与骨质疏松相关性研究[J].临床医药文献电子杂志, 2017, 4(18):3550-3551.
[39] D'Elia JA,Segal AR,Bayliss GP,et al.Sodium-glucose cotransporter-2 inhibition and acidosis in patients with type 2 diabetes:a review of US FDA data and possible conclusions[J].Int J Nephrol Renovasc Dis,2017,(10):153-158. doi:10.2147/IJNRD.S135899.
[40] Taylor SI,Blau JE,Rother KI.SGLT2 Inhibitors May Predispose to Ketoacidosis[J].J Clin Endocrinol Metab, 2015, 100(8):2849-2852.