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钠-葡萄糖协同转运蛋白2抑制剂的心血管结局:临床和临床前研究的全面综述

Cardiovascular outcomes of sodium-glucose cotransporter 2 inhibitors: A comprehensive review of clinical and preclinical studies.

作者信息

Ghosh Raktim Kumar, Bandyopadhyay Dhrubajyoti, Hajra Adrija, Biswas Monodeep, Gupta Anjan

机构信息

Department of Cardiovascular Medicine, St. Vincent Charity Medical Center, A Teaching Affiliate of Case Western Reserve University, Cleveland, OH, USA.

Department of Emergency Medicine, Lady Hardinge Medical College, New Delhi, India.

出版信息

Int J Cardiol. 2016 Jun 1;212:29-36. doi: 10.1016/j.ijcard.2016.02.134. Epub 2016 Mar 10.


DOI:10.1016/j.ijcard.2016.02.134
PMID:27017118
Abstract

Diabetes is a leading cause of morbidity and mortality worldwide. Management of diabetes is changing at a rapid pace. Three new classes of antidiabetic drugs including GLP-1 (Glucagon-like peptide 1), DPP-IV (Dipeptidyl peptidase IV) and SGLT2 (Sodium glucose cotransporter 2) inhibitors have been approved in the last few years. Treating diabetes with the antidiabetic drug does not always reduce the cardiovascular complications of diabetes. On the contrary, there was a huge controversy regarding the effect of rosiglitazone on cardiovascular risk reduction a few years ago. Since then, submission of postmarketing cardiovascular outcome study data has been mandated by US FDA and other drug regulatory agencies for newer antidiabetic medications. This is to avoid further premature claims regarding cardiovascular harm or safety of the newer classes. We already have some cardiovascular safety data available on DPP-IV and GLP-1 groups of medications. Dapagliflozin, canagliflozin, and empagliflozin are currently approved SGLT2 inhibitors. We do not have sufficient cardiovascular outcome data available for this novel class. However, this group of drugs, which act by increasing renal glucose excretion, have also shown some non-glycemic benefits including weight reduction, blood pressure control, diuretic action, renal protection, decrease in arterial stiffness and uric acid reduction. Empagliflozin, a new member of SGLT2 class, showed significant cardiovascular morbidity and mortality benefit in recently published EMPA-REG OUTCOME trial. The authors summarize all the published clinical and preclinical cardiovascular outcome data of SGLT2 inhibitors, including recently completed and ongoing major clinical trials in this comprehensive review.

摘要

糖尿病是全球发病和死亡的主要原因。糖尿病的管理正在迅速变化。在过去几年中,包括胰高血糖素样肽1(GLP-1)、二肽基肽酶IV(DPP-IV)和钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂在内的三类新型抗糖尿病药物已获批准。使用抗糖尿病药物治疗糖尿病并不总能降低糖尿病的心血管并发症。相反,几年前关于罗格列酮对降低心血管风险的作用存在巨大争议。从那时起,美国食品药品监督管理局(FDA)和其他药品监管机构要求提交新型抗糖尿病药物上市后的心血管结局研究数据。这是为了避免对新型药物的心血管危害或安全性提出进一步的过早断言。我们已经掌握了一些关于DPP-IV和GLP-1类药物的心血管安全性数据。达格列净、卡格列净和恩格列净是目前已获批准的SGLT2抑制剂。对于这一新型药物类别,我们尚无足够的心血管结局数据。然而,这类通过增加肾脏葡萄糖排泄起作用的药物也显示出一些非血糖益处,包括减轻体重、控制血压、利尿作用、肾脏保护、降低动脉僵硬度和降低尿酸。SGLT2类的新成员恩格列净在最近发表的EMPA-REG OUTCOME试验中显示出显著的心血管发病率和死亡率益处。作者在这篇全面综述中总结了SGLT2抑制剂所有已发表的临床和临床前心血管结局数据,包括最近完成和正在进行的主要临床试验。

相似文献

[1]
Cardiovascular outcomes of sodium-glucose cotransporter 2 inhibitors: A comprehensive review of clinical and preclinical studies.

Int J Cardiol. 2016-6-1

[2]
Can we go beyond surrogates?

J Diabetes. 2017-11

[3]
Impact of EMPA-REG OUTCOME on the management of type 2 diabetes mellitus: a review for primary care physicians.

Postgrad Med. 2016-11

[4]
Class effects of SGLT2 inhibitors on cardiorenal outcomes.

Cardiovasc Diabetol. 2019-8-5

[5]
Sodium Glucose Cotransporter 2 Inhibitors in the Treatment of Diabetes Mellitus: Cardiovascular and Kidney Effects, Potential Mechanisms, and Clinical Applications.

Circulation. 2016-9-6

[6]
Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular events, death, and major safety outcomes in adults with type 2 diabetes: a systematic review and meta-analysis.

Lancet Diabetes Endocrinol. 2016-3-18

[7]
SGLT2 inhibitors: new reports.

Med Lett Drugs Ther. 2015-10-12

[8]
EMPA-REG OUTCOME: The Nephrologist's Point of View.

Am J Med. 2017-6

[9]
EMPA-REG and Other Cardiovascular Outcome Trials of Glucose-lowering Agents: Implications for Future Treatment Strategies in Type 2 Diabetes Mellitus.

Clin Ther. 2016-6

[10]
EMPA-REG OUTCOME: The Nephrologist's Point of View.

Am J Cardiol. 2017-7-1

引用本文的文献

[1]
Functional annotation and enrichment analysis of differentially expressed serum proteins in patients with type 2 diabetes after dapagliflozin.

World J Diabetes. 2022-3-15

[2]
[Cardiovascular pharmacotherapy and coronary revascularization in end-stage renal failure].

Herz. 2019-11

[3]
Evaluation of the HbA1c Reduction Cut Point for a Nonglycemic Effect on Cardiovascular Benefit of Hypoglycemic Agents in Patients with Type 2 Diabetes Based on Endpoint Events.

Int J Endocrinol. 2018-4-19

[4]
The impact of oral anti-diabetic medications on heart failure: lessons learned from preclinical studies.

Heart Fail Rev. 2018-5

[5]
Adenosine monophosphate- activated protein kinase- based classification of diabetes pharmacotherapy.

J Postgrad Med. 2017

[6]
Role of SGLT2 Inhibitors in Patients with Diabetes Mellitus and Heart Failure.

Curr Heart Fail Rep. 2017-8

[7]
Blood pressure control in type 2 diabetic patients.

Cardiovasc Diabetol. 2017-1-6

[8]
Factors Affecting Canagliflozin-Induced Transient Urine Volume Increase in Patients with Type 2 Diabetes Mellitus.

Adv Ther. 2017-2

[9]
Empagliflozin lessened cardiac injury and reduced visceral adipocyte hypertrophy in prediabetic rats with metabolic syndrome.

Cardiovasc Diabetol. 2016-11-11

[10]
Strategies for Diabetes Management: Using Newer Oral Combination Therapies Early in the Disease.

Diabetes Ther. 2016-12

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