Application Prospect and Renal Outcomes of Novel Antidiabetic Agents in Patients with Type 2 Diabetes

doi:10.12114/j.issn.1007-9572.2021.00.452

Abstract

Abstract: Diabetic nephropathy，a common microvascular complication of type 2 diabetes，has become one of the common causes of end-stage renal disease in China.Several randomized controlled studies conducted in recent years found that，some novel anti-diabetic agents including dipeptidyl peptidase-4 inhibitor，sodium-glucose cotransporter 2 inhibitor and glucagon-like peptide-1 receptor agonist，have significant renal protection outcomes beside hypoglycemia effect in patients with type 2 diabetes，moreover sodium-glucose cotransporter 2 inhibitor and glucagon-like peptide-1 receptor agonist were recommended by clinical guideline or consensus in the prevention and delay of diabetic kidney disease.This paper summarized and analyzed the outcome of novel anti-diabetic agents in renal protection outcomes in patients with type 2 diabetes based on recent clinical guidelines and related randomized controlled trials，in order to provide a reference for the better application of novel anti-diabetic agents in practice.

Key words: Diabetes mellitus, type 2；Hypoglycemic agents；Glucagon-like peptide 1；Newer classes of antidiabetic agents；Kidney benefits；Editorial

摘要： 糖尿病肾病是2型糖尿病患者常见微血管并发症之一，也是我国终末期肾病患者的常见病因。近年来多项随机对照试验发现，二肽基肽酶4抑制剂、钠-葡萄糖共转动蛋白2抑制剂、胰高血糖素样肽1受体激动剂等新型降糖药物除降糖作用之外，部分还具有肾脏保护作用，其中钠-葡萄糖共转动蛋白2抑制剂、胰高血糖素样肽1受体激动剂已被相关临床指南或专家共识推荐用于2型糖尿病患者合并慢性肾脏病患者，为临床预防和治疗糖尿病肾病、延缓糖尿病肾病进展提供了新选择。本文结合最新指南及临床试验总结、分析了新型降糖药物对2型糖尿病患者的肾脏获益，以期为临床更好地应用新型降糖药物提供参考。

关键词: 糖尿病, 2型；降血糖药；胰高血糖素样肽1；新型降糖药物；肾脏获益；述评

YANG Guangran. Application Prospect and Renal Outcomes of Novel Antidiabetic Agents in Patients with Type 2 Diabetes　[J]. Chinese General Practice, 2021, 24(18): 2245-2250. DOI: 10.12114/j.issn.1007-9572.2021.00.452.
杨光燃. 新型降糖药物对2型糖尿病患者的肾脏获益及应用前景[J]. 中国全科医学, 2021, 24(18): 2245-2250. DOI: 10.12114/j.issn.1007-9572.2021.00.452.

References

［1］中华医学会糖尿病学分会.中国2型糖尿病防治指南（2017年版）［J］．中华糖尿病杂志，2018，10（1）：4-67．DOI：10.3760/cma.j.issn.1674-5809.2018.01.003.
［2］ZHANG J J，YANG L，HUANG J W，et al．Characteristics and comparison between diabetes mellitus and non-diabetes mellitus among chronic kidney disease patients：a cross-sectional study of the Chinese Cohort Study of Chronic Kidney Disease（C-STRIDE）［J］．Oncotarget，2017，8（63）：106324-106332．DOI：10.18632/oncotarget.22368.
［3］ZHANG L，LONG J，JIANG W，et al．Trends in chronic kidney disease in China［J］．New Engl J Med，2016，375（9）：905-906．DOI：10.1056/NEJMc1602469.
［4］中国医师协会内分泌代谢科医师分会.2型糖尿病合并慢性肾脏病患者口服降糖药治疗中国专家共识（2019年更新版）［J］．中华内分泌代谢杂志，2019，35（6）：447-454.
［5］ROSENSTOCK J，PERKOVIC V，JOHANSEN O E，et al．Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk：the CARMELINA randomized clinical trial［J］．JAMA，2019，321（1）：69-79．DOI：10.1001/jama.2018.18269.
［6］GROOP P H，COOPER M E，PERKOVIC V，et al．Linagliptin lowers albuminuria on top of recommended standard treatment in patients with type 2 diabetes and renal dysfunction［J］．Diabetes Care，2013，36（11）：3460-3468．DOI：10.2337/dc13-0323.
［7］COOPER M E，PERKOVIC V，MCGILL J B，et al．Kidney disease end points in a pooled analysis of individual patient-level data from a Large clinical trials program of the dipeptidyl peptidase 4 inhibitor linagliptin in type 2 diabetes［J］．Am J Kidney Dis，2015，66（3）：441-449．DOI：10.1053/j.ajkd.2015.03.024.
［8］GROOP P H，COOPER M E，PERKOVIC V，et al．Linagliptin and its effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction：the randomized MARLINA-T2D trial［J］．Diabetes Obes Metab，2017，19（11）：1610-1619．DOI：10.1111/dom.13041.
［9］MOSENZON O，LEIBOWITZ G，BHATT D L，et al．Effect of saxagliptin on renal outcomes in the SAVOR-TIMI 53 trial［J］．Diabetes care，2017，40（1）：69-76．DOI：10.2337/dc16-0621.
［10］MOHSEN M，ELBERRY A A，MOHAMED RABEA A，et al．Saxagliptin and vildagliptin lowered albuminuria in patients with diabetes and hypertension independent on glycaemic control［J］．Int J Clin Pract，2020：e13769．DOI：10.1111/ijcp.13769.
［11］TANI S，NAGAO K，HIRAYAMA A.Association between urinary albumin excretion and low-density lipoprotein heterogeneity following treatment of type 2 diabetes patients with the dipeptidyl peptidase-4 inhibitor，vildagliptin：a pilot study［J］．Am J Cardiovasc Drugs，2013，13（6）：443-450．DOI：10.1007/s40256-013-0043-2.
［12］MORI H，OKADA Y，ARAO T，et al．Sitagliptin improves albuminuria in patients with type 2 diabetes mellitus［J］．J Diabetes Investig，2014，5（3）：313-319．DOI：10.1111/jdi.12142.
［13］HATTORI S.Sitagliptin reduces albuminuria in patients with type 2 diabetes［J］．Endocr J，2011，58（1）：69-73．DOI：10.1507/endocrj.k10e-382.
［14］CORNEL J H，BAKRIS G L，STEVENS S R，et al．Effect of sitagliptin on kidney function and respective cardiovascular outcomes in type 2 diabetes：outcomes from TECOS［J］．Diabetes care，2016，39（12）：2304-2310．DOI：10.2337/dc16-1415.
［15］SAKATA K，HAYAKAWA M，YANO Y，et al．Efficacy of alogliptin，a dipeptidyl peptidase-4 inhibitor，on glucose parameters，the activity of the advanced glycation end product（AGE）-receptor for AGE（RAGE）axis and albuminuria in Japanese type 2 diabetes［J］．Diabetes Metab Res Rev，2013，29（8）：624-630．DOI：10.1002/dmrr.2437.
［16］PERKOVIC V，JARDINE M J，NEAL B，et al．Canagliflozin and renal outcomes in type 2 diabetes and nephropathy［J］．New Engl J Med，2019，380（24）：2295-2306．DOI：10.1056/NEJMoa1811744.
［17］NEAL B，PERKOVIC V，MAHAFFEY K W，et al．Canagliflozin and cardiovascular and renal events in type 2 diabetes［J］．New Engl J Med，2017，377（7）：644-657．DOI：10.1056/NEJMoa1611925.
［18］HEERSPINK H J L，STEFáNSSON B V，CORREA-ROTTER R，et al．Dapagliflozin in patients with chronic kidney disease［J］．New Engl J Med，2020，383（15）：1436-1446．DOI：10.1056/NEJMoa2024816.
［19］MOSENZON O，WIVIOTT S D，CAHN A，et al．Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes：an analysis from the DECLARE-TIMI 58 randomised trial［J］．Lancet Diabetes Endocrinol，2019，7（8）：606-617．DOI：10.1016/S2213-8587（19）30180-9.
［20］POLLOCK C，STEFáNSSON B，REYNER D，et al．Albuminuria-lowering effect of dapagliflozin alone and in combination with saxagliptin and effect of dapagliflozin and saxagliptin on glycaemic control in patients with type 2 diabetes and chronic kidney disease（DELIGHT）：a randomised，double-blind，placebo-controlled trial［J］．Lancet Diabetes Endocrinol，2019，7（6）：429-441．DOI：10.1016/S2213-8587（19）30086-5.
［21］WANNER C，INZUCCHI S E，LACHIN J M，et al．Empagliflozin and progression of kidney disease in type 2 diabetes［J］．New Engl J Med，2016，375（4）：323-334．DOI：10.1056/NEJMoa1515920.
［22］CHERNEY D Z I，ZINMAN B，INZUCCHI S E，et al．Effects of empagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and established cardiovascular disease：an exploratory analysis from the EMPA-REG OUTCOME randomised，placebo-controlled trial［J］．Lancet Diabetes Endocrinol，2017，5（8）：610-621．DOI：10.1016/S2213-8587（17）30182-1.
［23］WELDEGIORGIS M，DE ZEEUW D，HEERSPINK H J L.Renal end points in clinical trials of kidney disease［J］．Current Opin Nephrol Hypertens，2015，24（3）：284-289．DOI：10.1097/MNH.0000000000000118.
［24］STANDL E，SCHNELL O.Treatment paradigm shifting implications of recent cardiovascular outcome trials：core insights on the brink of the 2020ies［J］．Diabetes Res Clin Pract，2020，161：108054．DOI：10.1016/j.diabres.2020.108054.
［25］中华医学会糖尿病学分会，中华医学会内分泌学分会.中国成人2型糖尿病合并心肾疾病患者降糖药物临床应用专家共识［J］．中华糖尿病杂志，2020，12（6）：369-381．DOI：10.3760/cma.j.cn115791-20200419-00233.
Chinese Diabetes Society，Endocrinology Branch of Chinese Medical Association.Expert consensus on glucose-lowering pharmacotherapies in Chinese adults with type 2 diabetes and cardiovascular disease or chronic kidney disease［J］．Chinese Journal of Diabetes Mellitus，2020，12（6）：369-381．DOI：10.3760/cma.j.cn115791-20200419-00233.
［26］Kidney Disease：Improving Global Outcomes Diabetes Work Group.KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney DISEASE［J］．Kidney Int，2020，98（4S）：S1-115．DOI：10.1016/j.kint.2020.06.019.
［27］American Diabetes Association.11.Microvascular complications and foot care：standards of medical care in diabetes-2021［J］．Diabetes Care，2021，44（Suppl 1）：S151-167．DOI：10.2337/dc21-S011.
［28］MANN J F E，?RSTED D D，BROWN-FRANDSEN K，et al．Liraglutide and renal outcomes in type 2 diabetes［J］．New Engl J Med，2017，377（9）：839-848．DOI：10.1056/NEJMoa1616011.
［29］GERSTEIN H C，COLHOUN H M，DAGENAIS G R，et al．Dulaglutide and renal outcomes in type 2 diabetes：an exploratory analysis of the REWIND randomised，placebo-controlled trial［J］．Lancet，2019，394（10193）：131-138．DOI：10.1016/S0140-6736（19）31150-X.
［30］MARSO S P，BAIN S C，CONSOLI A，et al．Semaglutide and cardiovascular outcomes in patients with type 2 diabetes［J］．New Engl J Med，2016，375（19）：1834-1844．DOI：10.1056/NEJMoa1607141.
［31］MUSKIET M H A，TONNEIJCK L，HUANG Y，et al．Lixisenatide and renal outcomes in patients with type 2 diabetes and acute coronary syndrome：an exploratory analysis of the ELIXA randomised，placebo-controlled trial［J］．Lancet Diabetes Endocrinol，2018，6（11）：859-869．DOI：10.1016/S2213-8587（18）30268-7.
［32］TUTTLE K R，LAKSHMANAN M C，RAYNER B，et al．Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease（AWARD-7）：a multicentre，open-label，randomised trial［J］．Lancet Diabetes Endocrinol，2018，6（8）：605-617．DOI：10.1016/S2213-8587（18）30104-9.
［33］ZHANG H，ZHANG X，HU C，et al．Exenatide reduces urinary transforming growth factor-β1 and typeⅣ collagen excretion in patients with type 2 diabetes and microalbuminuria［J］．Kidney Blood Press Res，2012，35（6）：483-488.
［34］IMAMURA S，HIRAI K，HIRAI A.The glucagon-like peptide-1 receptor agonist，liraglutide，attenuates the progression of overt diabetic nephropathy in type 2 diabetic patients［J］．Tohoku J Exp Med，2013，231（1）：57-61．DOI：10.1620/tjem.231.57.
［35］纪立农，邹大进，洪天配，等．GLP-1受体激动剂临床应用专家指导意见［J］．中国糖尿病杂志，2018，26（5）：353-361．DOI：10.3969/j.issn.1006-6187.2018.05.001.

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