New Developments in Antidiabetic Agents from the Perspective of Cardiovascular Outcomes

doi:10.12114/j.issn.1007-9572.2021.00.447

Abstract

Abstract: Patients with diabetes mellitus have a significantly higher risk of developing cardiovascular disease（CVD），and CVD is the leading cause of death in adults with type 2 diabetes mellitus（T2DM）.Traditional hypoglycemic drugs，despite their significant hypoglycemic efficacy，lack good evaluation of cardiovascular outcomes.In contrast，new hypoglycemic drugs have undergone large clinical trials before being approved，to ensure their therapeutic efficacy and safety for cardiovascular outcomes.This review introduces the latest clinical developments in traditional and new antidiabetic medications in terms of cardiovascular outcomes （that is，cardiovascular safety），and proposes that some new drugs，such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists，have demonstrated good cardiovascular protection，and their therapeutic roles have been raised in multiple guidelines，becoming important therapeutic options for adults with T2DM and CVD.This review is expected to provide more diabetes treatment strategies for clinicians.

Key words: Diabetes mellitus, type 2；Drug therapy；Hypoglycemic agents；Cardiovascular diseases；Adverse drug reaction；Review

摘要： 糖尿病患者发生冠心病的风险较非糖尿病患者明显升高，且心血管疾病是2型糖尿病患者最主要的致死原因。传统降糖药物尽管降糖疗效显著，但缺乏对心血管结局的良好评估。新型降糖药物经过大型临床试验确保了疗效和对心血管结局的安全性。本文从降糖药物对心血管结局影响的角度，介绍传统降糖药物及新型降糖药物在糖尿病治疗中的心血管安全性，指出某些新型降糖药物如钠-葡萄糖共转运蛋白2抑制剂（SGLT-2i）和胰高血糖素样肽1受体激动剂（GLP-1RAs）在2型糖尿病患者中具有良好心血管保护作用，其治疗地位在多项指南中得到提升，成为2型糖尿病合并心血管疾病患者的重要选择。本文结合多项国内外最新临床证据对糖尿病治疗药物对心血管结局的影响进行分析、总结，以期为临床医疗工作者制定糖尿病治疗策略提供参考。

关键词: 糖尿病, 2型；药物疗法；降血糖药；心血管疾病；药物不良反应；综述

ZHANG Xuane,ZHOU Zunhai. New Developments in Antidiabetic Agents from the Perspective of Cardiovascular Outcomes　[J]. Chinese General Practice, 2021, 24(18): 2251-2259. DOI: 10.12114/j.issn.1007-9572.2021.00.447.
张玄娥,周尊海. 从心血管结局看降糖药物治疗的新进展[J]. 中国全科医学, 2021, 24(18): 2251-2259. DOI: 10.12114/j.issn.1007-9572.2021.00.447.

References

［1］HAFFNER S M，LEHTO S，R?NNEMAA T，et al．Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction［J］．N Engl J Med，1998，339（4）：229-234．DOI：10.1056/NEJM199807233390404.
［2］COLLABORATION E R F，DI ANGELANTONIO E，KAPTOGE S，et al．Association of cardiometabolic multimorbidity with mortality［J］．JAMA，2015，314（1）：52-60．DOI：10.1001/jama.2015.7008.
［3］Diabetes Control and Complications Trial Research Group，NATHAN D M，GENUTH S，et al．The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus［J］．N Engl J Med，1993，329（14）：977-986．DOI：10.1056/NEJM199309303291401.
［4］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）［J］．Lancet，1998，352（9131）：837-853.
［5］TAHRANI A A，BAILEY C J，DEL PRATO S，et al．Management of type 2 diabetes：new and future developments in treatment［J］．Lancet，2011，378（9786）：182-197．DOI：10.1016/s0140-6736（11）60207-9.
［6］NISSEN S E，WOLSKI K.Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes［J］．J Vasc Surg，2007，46（3）：608．DOI：10.1016/j.jvs.2007.07.011.
［7］Regulatory watch：FDA issues guidance for cardiovascular risk assessment of novel antidiabetic agents［J］．Nat Rev Drug Discov，2009，8（2）：99．DOI：10.1038/nrd2823.
［8］RENA G，LANG C C.Repurposing metformin for cardiovascular disease［J］．Circulation，2018，137（5）：422-424．DOI：10.1161/circulationaha.117.031735.
［9］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）［J］．Lancet，1998，352（9131）：854-865.
［10］HOLMAN R R，PAUL S K，BETHEL M A，et al．10-year follow-up of intensive glucose control in type 2 diabetes［J］．N Engl J Med，2008，359（15）：1577-1589．DOI：10.1056/NEJMoa0806470.
［11］PETRIE J R，CHATURVEDI N，FORD I，et al．Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes （REMOVAL）：a double-blind，randomised，placebo-controlled trial［J］．Lancet Diabetes Endocrinol，2017，5（8）：597-609．DOI：10.1016/S2213-8587（17）30194-8.
［12］LAMANNA C，MONAMI M，MARCHIONNI N，et al．Effect of metformin on cardiovascular events and mortality：a meta-analysis of randomized clinical trials［J］．Diabetes Obes Metab，2011，13（3）：221-228．DOI：10.1111/j.1463-1326.2010.01349.x.
［13］American Diabetes Association.9.pharmacologic approaches to glycemic treatment：standards of medical care in diabetes-2020［J］．Diabetes Care，2020，43（suppl 1）：S98-110．DOI：10.2337/dc20-s009.
［14］SIGAL R J，EL-HASHIMY M，MARTIN B C，et al．Acute postchallenge hyperinsulinemia predicts weight gain：a prospective study［J］．Diabetes，1997，46（6）：1025-1029．DOI：10.2337/diab.46.6.1025.
［15］ADVANCE Collaborative Group，PATEL A，MACMAHON S，et al．Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes［J］．N Engl J Med，2008，358（24）：2560-2572．DOI：10.1056/NEJMoa0802987.
［16］RENDELL M.The role of sulphonylureas in the management of type 2 diabetes mellitus［J］．Drugs，2004，64（12）：1339-1358．DOI：10.2165/00003495-200464120-00006.
［17］MEINERT C L，KNATTERUD G L，PROUT T E，et al．A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetesⅡ.Mortality results［J］．Diabetes，1970，19（Suppl）：789-783.
［18］MONAMI M，GENOVESE S，MANNUCCI E.Cardiovascular safety of sulfonylureas：a meta-analysis of randomized clinical trials［J］．Diabetes Obes Metab，2013，15（10）：938-953．DOI：10.1111/dom.12116.
［19］VARVAKI RADOS D，CATANI PINTO L，RECK REMONTI L，et al．The association between sulfonylurea use and all-cause and cardiovascular mortality：a meta-analysis with trial sequential analysis of randomized clinical trials［J］．PLoS Med，2016，13（4）：e1001992．DOI：10.1371/journal.pmed.1001992.
［20］Navigator Study Group，HOLMAN R R，HAFFNER S M，et al．Effect of nateglinide on the incidence of diabetes and cardiovascular events［J］．N Engl J Med，2010，362（16）：1463-1476．DOI：10.1056/nejmoa1001122.
［21］AOKI K，SATO H，TERAUCHI Y.Usefulness of antidiabetic alpha-glucosidase inhibitors：a review on the timing of administration and effects on gut hormones［J］．Endocr J，2019，66（5）：395-401．DOI：10.1507/endocrj.ej19-0041.
［22］NEPAL M R，KANG M J，KIM G H，et al．Role of intestinal microbiota in metabolism of voglibose in vitro and in vivo［J］．Diabetes Metab J，2020，44（6）：908-918．DOI：10.4093/dmj.2019.0147.
［23］HANEFELD M，CAGATAY M，PETROWITSCH T，et al．Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients：meta-analysis of seven long-term studies［J］．Eur Heart J，2004，25（1）：10-16．DOI：10.1016/s0195-668x（03）00468-8.
［24］HOLMAN R R，COLEMAN R L，CHAN J C N，et al．Effects of acarbose on cardiovascular and diabetes outcomes in patients with coronary heart disease and impaired glucose tolerance （ACE）：a randomised，double-blind，placebo-controlled trial［J］．Lancet Diabetes Endocrinol，2017，5（11）：877-886．DOI：10.1016/s2213-8587（17）30309-1.
［25］YANG W Y，LIU J，SHAN Z Y，et al．Acarbose compared with metformin as initial therapy in patients with newly diagnosed type 2 diabetes：an open-label，non-inferiority randomised trial［J］．Lancet Diabetes Endocrinol，2014，2（1）：46-55．DOI：10.1016/s2213-8587（13）70021-4.
［26］NISSEN S E，WOLSKI K.Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes［J］．J Vasc Surg，2007，46（3）：608．DOI：10.1016/j.jvs.2007.07.011.
［27］HOME P D，POCOCK S J，BECK-NIELSEN H，et al．Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes （RECORD）：a multicentre，randomised，open-label trial［J］．Lancet，2009，373（9681）：2125-2135．DOI：10.1016/S0140-6736（09）60953-3.
［28］DORMANDY J A，CHARBONNEL B，ECKLAND D J A，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 randomised controlled trial［J］．Lancet，2005，366（9493）：1279-1289．DOI：10.1016/S0140-6736（05）67528-9.
［29］KERNAN W N，VISCOLI C M，FURIE K L，et al．Pioglitazone after ischemic stroke or transient ischemic attack［J］．N Engl J Med，2016，374（14）：1321-1331．DOI：10.1056/NEJMoa1506930.
［30］RIZOS C V，KEI A，ELISAF M S.The current role of thiazolidinediones in diabetes management［J］．Arch Toxicol，2016，90（8）：1861-1881．DOI：10.1007/s00204-016-1737-4.
［31］RIZOS C V，LIBEROPOULOS E N，MIKHAILIDIS D P，et al．Pleiotropic effects of thiazolidinediones［J］．Expert Opin Pharmacother，2008，9（7）：1087-1108．DOI：10.1517/14656566.9.7.1087.
［32］GOLDBERG R B，KENDALL D M，DEEG M A，et al．A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia［J］．Diabetes Care，2005，28（7）：1547-1554．DOI：10.2337/diacare.28.7.1547.
［33］BILLINGTON E O，GREY A，BOLLAND M J.The effect of thiazolidinediones on bone mineral density and bone turnover：systematic review and meta-analysis［J］．Diabetologia，2015，58（10）：2238-2246．DOI：10.1007/s00125-015-3660-2.
［34］HIPPISLEY-COX J，COUPLAND C.Diabetes treatments and risk of heart failure，cardiovascular disease，and all cause mortality：cohort study in primary care［J］．BMJ，2016，354：i3477．DOI：10.1136/bmj.i3477.
［35］INVESTIGATORS O T，GERSTEIN H C，BOSCH J，et al．Basal insulin and cardiovascular and other outcomes in dysglycemia［J］．N Engl J Med，2012，367（4）：319-328．DOI：10.1056/NEJMoa1203858.
［36］MARSO S P，MCGUIRE D K，ZINMAN B，et al．Efficacy and safety of degludec versus glargine in type 2 diabetes［J］．N Engl J Med，2017，377（8）：723-732．DOI：10.1056/NEJMoa1615692.
［37］AVOGARO A，FADINI G P.The effects of dipeptidyl peptidase-4 inhibition on microvascular diabetes complications［J］．Diabetes Care，2014，37（10）：2884-2894．DOI：10.2337/dc14-0865.
［38］GREEN J B，BETHEL M A，ARMSTRONG P W，et al．Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes［J］．N Engl J Med，2015，373（3）：232-242．DOI：10.1056/NEJMoa1501352.
［39］ZANNAD F，CANNON C P，CUSHMAN W C，et al．Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE：a multicentre，randomised，double-blind trial［J］．Lancet，2015，385（9982）：2067-2076．DOI：10.1016/s0140-6736（14）62225-x.
［40］MCGUIRE D K，VAN DE WERF F，ARMSTRONG P W，et al．Association between sitagliptin use and heart failure hospitalization and related outcomes in type 2 diabetes mellitus：secondary analysis of a randomized clinical trial［J］．JAMA Cardiol，2016，1（2）：126-135．DOI：10.1001/jamacardio.2016.0103.
［41］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.
［42］ROSENSTOCK J，KAHN S E，JOHANSEN O E，et al．Effect of linagliptin vs glimepiride on major adverse cardiovascular outcomes in patients with type 2 diabetes：the CAROLINA randomized clinical trial［J］．JAMA，2019．DOI：10.1001/jama.2019.13772．DOI：10.1001/jama.2019.13772.
［43］ADVANI A，BUGYEI-TWUM A，CONNELLY K A.Cardiovascular effects of incretins in diabetes［J］．Can J Diabetes，2013，37（5）：309-314．DOI：10.1016/j.jcjd.2013.06.010.
［44］DEL OLMO-GARCIA M I，MERINO-TORRES J F.GLP-1 receptor agonists and cardiovascular disease in patients with type 2 diabetes［J］．J Diabetes Res，2018，2018：4020492．DOI：10.1155/2018/4020492.
［45］PFEFFER M A，CLAGGETT B，DIAZ R，et al．Lixisenatide in patients with type 2 diabetes and acute coronary syndrome［J］．N Engl J Med，2015，373（23）：2247-2257．DOI：10.1056/NEJMoa1509225.
［46］HOLMAN R R，BETHEL M A，MENTZ R J，et al．Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes［J］．N Engl J Med，2017，377（13）：1228-1239．DOI：10.1056/NEJMoa1612917.
［47］MARSO S P，BAIN S C，CONSOLI A，et al．Semaglutide and cardiovascular outcomes in patients with type 2 diabetes［J］．N Engl J Med，2016，375（19）：1834-1844．DOI：10.1056/NEJMoa1607141.
［48］MARSO S P，DANIELS G H，BROWN-FRANDSEN K，et al．Liraglutide and cardiovascular outcomes in type 2 diabetes［J］．N Engl J Med，2016，375（4）：311-322．DOI：10.1056/NEJMoa1603827.
［49］HERNANDEZ A F，GREEN J B，JANMOHAMED S，et al．Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease （Harmony Outcomes）：a double-blind，randomised placebo-controlled trial［J］．Lancet，2018，392（10157）：1519-1529．DOI：10.1016/S0140-6736（18）32261-X.
［50］GERSTEIN H C，COLHOUN H M，DAGENAIS G R，et al．Dulaglutide and cardiovascular outcomes in type 2 diabetes （REWIND）：a double-blind，randomised placebo-controlled trial［J］．Lancet，2019，394（10193）：121-130．DOI：10.1016/S0140-6736（19）31149-3.
［51］THETHI T K，PRATLEY R，MEIER J J.Efficacy，safety and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes：the PIONEER programme［J］．Diabetes Obes Metab，2020，22（8）：1263-1277．DOI：10.1111/dom.14054.
［52］DRUCKER D J.The cardiovascular biology of glucagon-like peptide-1［J］．Cell Metab，2016，24（1）：15-30．DOI：10.1016/j.cmet.2016.06.009.
［53］NEWMAN J D，VANI A K，ALEMAN J O，et al．The changing landscape of diabetes therapy for cardiovascular risk reduction：JACC state-of-the-art review［J］．J Am Coll Cardiol，2018，72（15）：1856-1869．DOI：10.1016/j.jacc.2018.07.071.
［54］MONAMI M，DICEMBRINI I，MANNUCCI E.Effects of SGLT-2 inhibitors on mortality and cardiovascular events：a comprehensive meta-analysis of randomized controlled trials［J］．Acta Diabetol，2017，54（1）：19-36．DOI：10.1007/s00592-016-0892-7.
［55］PACKER M.Have dipeptidyl peptidase-4 inhibitors ameliorated the vascular complications of type 2 diabetes in large-scale trials？The potential confounding effect of stem-cell chemokines［J］．Cardiovasc Diabetol，2018，17（1）：9．DOI：10.1186/s12933-017-0648-x.
［56］VETTOR R，INZUCCHI S E，FIORETTO P.The cardiovascular benefits of empagliflozin：SGLT2-dependent and -independent effects［J］．Diabetologia，2017，60（3）：395-398．DOI：10.1007/s00125-016-4194-y.
［57］GUTHRIE R.Canagliflozin and cardiovascular and renal events in type 2 diabetes［J］．Postgrad Med，2018，130（2）：149-153．DOI：10.1080/00325481.2018.1423852.
［58］MAHAFFEY K W，NEAL B，PERKOVIC V，et al．Canagliflozin for primary and secondary prevention of cardiovascular events：results from the CANVAS program （canagliflozin cardiovascular assessment study）［J］．Circulation，2018，137（4）：323-334．DOI：10.1161/CIRCULATIONAHA.117.032038.
［59］FURTADO R H M，BONACA M P，RAZ I，et al．Dapagliflozin and cardiovascular outcomes in patients with type 2 diabetes mellitus and previous myocardial infarction［J］．Circulation，2019，139（22）：2516-2527．DOI：10.1161/CIRCULATIONAHA.119.039996.
［60］KATO E T，SILVERMAN M G，MOSENZON O，et al．Effect of dapagliflozin on heart failure and mortality in type 2 diabetes mellitus［J］．Circulation，2019，139（22）：2528-2536．DOI：10.1161/CIRCULATIONAHA.119.040130.
［61］VERMA S，MCMURRAY J J V.The serendipitous story of SGLT2 inhibitors in heart failure［J］．Circulation，2019，139（22）：2537-2541．DOI：10.1161/circulationaha.119.040514.
［62］MCMURRAY J J V，SOLOMON S D，INZUCCHI S E，et al. Dapagliflozin in patients with heart failure and reduced ejection fraction［J］．N Engl J Med，2019，381（21）：1995-2008．DOI：10.1056/NEJMoa1911303.
［63］PERKOVIC V，JARDINE MJ，NEAL B，et al.Canagliflozin and renal outcomes in type 2 diabetes and nephropathy［J］．N Engl J Med，2019，380（24）：2295-2306．DOI：10.1056/NEJMoa1811744.
［64］VERMA S.Potential mechanisms of sodium-glucose Co-transporter 2 inhibitor-related cardiovascular benefits［J］．Am J Cardiol，2019，124（Suppl 1）：S36-44．DOI：10.1016/j.amjcard.2019.10.028.
［65］JANSSENS B，CAERELS S，MATHIEU C.SGLT inhibitors in type 1 diabetes：weighing efficacy and side effects［J］．Ther Adv Endocrinol Metab，2020，11：2042018820938545．DOI：10.1177/2042018820938545.

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