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Current Diabetes Reviews

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ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

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Diabetes and Cardiorenal Complications: A Clinical Review of Existing Therapies and Novel Combinations, Focusing on SGLT2 Inhibitors

Author(s): Ajinath Kale, Anshima Sharma, Hans-Joachim Anders and Anil Bhanudas Gaikwad*

Volume 19, Issue 8, 2023

Published on: 09 September, 2022

Article ID: e160822207546 Pages: 13

DOI: 10.2174/1573399819666220816145907

Price: $65

Abstract

Type 2 diabetes mellitus (T2DM) is a set of metabolic disorders specified by hyperglycemia as a result of abnormalities in insulin secretion or sensitivity. Chronic kidney disease (CKD) and cardiovascular disease (CVD) are the widespread co-morbidities of T2DM and share risk factors for onset and progression. Despite numerous mono- and combination therapies exist, the progression of diabetes complications remains a global health concern. Treatment options for diabetic- CKD and CVD include drugs targeting hyperglycemia, hypertension, albuminuria, hyperlipidemia and the renin-angiotensin aldosterone system (RAAS). The sodium-glucose co-transporter 2 channel (SGLT2) is abundantly present in proximal tubules of the kidney and its capacity to recover glucose and sodium from the glomerular filtrate limits urinary glucose and sodium excretion. SGLT2 inhibitors (SGLT2i) reduce sodium and glucose reabsorption in the proximal and thus increase urinary glucose excretion in T2DM. SGLT2i monotherapy can improve but dual SGLT2/RAAS inhibition or SGLT2i along with other classes of drugs are more effective in protecting the kidneys and the cardiovascular system in patients with and without diabetes. Combinations such as empagliflozin and linagliptin, ertugliflozin and metolazone, dapagliflozin and sacubitril- valsartan and many more show promising results. Here, we have reviewed the ongoing and completed clinical trials, addressed current theories, and discussed necessary future research to explain the possible risks and benefits of using an SGLT2i alone and in combination with existing antidiabetic drugs and drugs acting on the cardiovascular system.

Keywords: SGLT2 inhibitors, diabetes, diabetic kidney diseases, diabetic cardiovascular disease, chronic kidney disease.

[1]
Tentolouris A, Eleftheriadou I, Athanasakis K, et al. Prevalence of diabetes mellitus as well as cardiac and other main comorbidities in a representative sample of the adult Greek population in comparison with the general population. Hellenic J Cardiol 2020; 61(1): 15-22.
[http://dx.doi.org/10.1016/j.hjc.2018.04.008] [PMID: 29729413]
[2]
Xu G, Liu B, Sun Y, et al. Prevalence of diagnosed type 1 and type 2 diabetes among US adults in 2016 and 2017: Population based study. BMJ 2018; 362: k1497.
[http://dx.doi.org/10.1136/bmj.k1497] [PMID: 30181166]
[3]
Zelniker TA, Braunwald E. Cardiac and renal effects of sodium-glucose co-transporter 2 inhibitors in diabetes: JACC state-of-the-art review. J Am Coll Cardiol 2018; 72(15): 1845-55.
[4]
Jha V, Garcia-Garcia G, Iseki K, et al. Chronic kidney disease: Global dimension and perspectives. Lancet 2013; 382(9888): 260-72.
[http://dx.doi.org/10.1016/S0140-6736(13)60687-X] [PMID: 23727169]
[5]
Kale A, Sankrityayan H, Anders HJ, Bhanudas Gaikwad A. Klotho: A possible mechanism of action of SGLT2 inhibitors preventing episodes of acute kidney injury and cardiorenal complications of diabetes. Drug Discov Today 2021; 26(8): 1963-71.
[http://dx.doi.org/10.1016/j.drudis.2021.04.007] [PMID: 33862192]
[6]
Heerspink HJL, Kosiborod M, Inzucchi SE, Cherney DZI. Renoprotective effects of sodium-glucose cotransporter-2 inhibitors. Kidney Int 2018; 94(1): 26-39.
[http://dx.doi.org/10.1016/j.kint.2017.12.027] [PMID: 29735306]
[7]
Wanner Ch, Inzucchi SE, Zinman B. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 2016; 375(18): 1801-2.
[http://dx.doi.org/10.1056/NEJMoa1515920] [PMID: 27806236]
[8]
Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017; 377(7): 644-57.
[http://dx.doi.org/10.1056/NEJMoa1611925] [PMID: 28605608]
[9]
Hershon KS. Options for empagliflozin in combination therapy in type 2 diabetes mellitus. Int J Gen Med 2016; 9: 155-72.
[PMID: 27307761]
[10]
Grunberger G. Should side effects influence the selection of antidiabetic therapies in type 2 diabetes? Curr Diab Rep 2017; 17(4): 21.
[http://dx.doi.org/10.1007/s11892-017-0853-8] [PMID: 28293908]
[11]
Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia 2017; 60(9): 1577-85.
[http://dx.doi.org/10.1007/s00125-017-4342-z] [PMID: 28776086]
[12]
Akmal M, Wadhwa R. StatPearls Publishing 2021; LLC: 2021.
[13]
Davidson MA, Mattison DR, Azoulay L, Krewski D. Thiazolidinedione drugs in the treatment of type 2 diabetes mellitus: Past, present and future. Crit Rev Toxicol 2018; 48(1): 52-108.
[http://dx.doi.org/10.1080/10408444.2017.1351420] [PMID: 28816105]
[14]
DeFronzo RA, Andres R, Bedsoe TA, Boden G, Faloona GA, Tobin JD. A test of the hypothesis that the rate of fall in glucose concentration triggers counterregulatory hormonal responses in man. Diabetes 1977; 26(5): 445-52.
[http://dx.doi.org/10.2337/diab.26.5.445] [PMID: 856648]
[15]
de Boer IH, Kahn SE. SGLT2 inhibitors-sweet success for diabetic kidney disease? J Am Soc Nephrol 2017; 28(1): 7-10.
[http://dx.doi.org/10.1681/ASN.2016060650]
[16]
Jabbour SA, Hardy E, Sugg J, Parikh S, Group S. Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: A 24-week, multicenter, randomized, double-blind, placebo-controlled study. Diabetes Care 2014; 37(3): 740-50.
[http://dx.doi.org/10.2337/dc13-0467] [PMID: 24144654]
[17]
Filippatos TD, Liontos A, Papakitsou I, Elisaf MS. SGLT2 inhibitors and cardioprotection: A matter of debate and multiple hypotheses. Postgrad Med 2019; 131(2): 82-8.
[http://dx.doi.org/10.1080/00325481.2019.1581971] [PMID: 30757937]
[18]
Seidu S, Kunutsor SK. Benefits and harms of sodium-glucose co-transporter-2 inhibitors (SGLT2-I) and renin-angiotensin-aldosterone system inhibitors (RAAS-I) versus SGLT2-Is alone in patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials. Endocrinol Diabetes Metab 2022; 5(1): e00303.
[19]
Jabbour SA, Frías JP, Hardy E, et al. Safety and efficacy of exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy: 52-week results of the DURATION-8 randomized controlled trial. Diabetes Care 2018; 41(10): 2136-46.
[http://dx.doi.org/10.2337/dc18-0680] [PMID: 30082326]
[20]
Cherney DZI, Cooper ME, Tikkanen I, et al. Pooled analysis of Phase III trials indicate contrasting influences of renal function on blood pressure, body weight, and HbA1c reductions with empagliflozin. Kidney Int 2018; 93(1): 231-44.
[http://dx.doi.org/10.1016/j.kint.2017.06.017] [PMID: 28860019]
[21]
Han E, Shin E, Kim G, et al. Combining SGLT2 inhibition with a thiazolidinedione additively attenuate the very early phase of diabetic nephropathy progression in type 2 diabetes mellitus. Front Endocrinol (Lausanne) 2018; 9: 412.
[http://dx.doi.org/10.3389/fendo.2018.00412] [PMID: 30072956]
[22]
Alicic RZ, Rooney MT, Tuttle KR. Diabetic kidney disease: Challenges, progress, and possibilities. Clin J Am Soc Nephrol 2017; 12(12): 2032-45.
[http://dx.doi.org/10.2215/CJN.11491116] [PMID: 28522654]
[23]
Thomas MC, Cooper ME, Zimmet P. Changing epidemiology of type 2 diabetes mellitus and associated chronic kidney disease. Nat Rev Nephrol 2016; 12(2): 73-81.
[http://dx.doi.org/10.1038/nrneph.2015.173] [PMID: 26553517]
[24]
Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, et al. Chronic kidney disease and cardiovascular risk: Epidemiology, mechanisms, and prevention. Lancet 2013; 382(9889): 339-52.
[http://dx.doi.org/10.1016/S0140-6736(13)60595-4] [PMID: 23727170]
[25]
Chen Y, Lee K, Ni Z, He JC. Diabetic kidney disease: Challenges, advances, and opportunities. Kidney Dis 2020; 6(4): 215-25.
[http://dx.doi.org/10.1159/000506634] [PMID: 32903946]
[26]
Singh M, Kumar A. Risks associated with SGLT2 inhibitors: An overview. Curr Drug Saf 2018; 13(2): 84-91.
[http://dx.doi.org/10.2174/1574886313666180226103408] [PMID: 29485006]
[27]
Andrésdóttir G, Jensen ML, Carstensen B, et al. Improved survival and renal prognosis of patients with type 2 diabetes and nephropathy with improved control of risk factors. Diabetes Care 2014; 37(6): 1660-7.
[http://dx.doi.org/10.2337/dc13-2036] [PMID: 24623028]
[28]
de Boer IH, Rue TC, Hall YN, Heagerty PJ, Weiss NS, Himmelfarb J. Temporal trends in the prevalence of diabetic kidney disease in the United States. JAMA 2011; 305(24): 2532-9.
[http://dx.doi.org/10.1001/jama.2011.861] [PMID: 21693741]
[29]
Badal SS, Danesh FR. New insights into molecular mechanisms of diabetic kidney disease. Am J Kidney Dis 2014; 63(2) (Suppl. 2): S63-83.
[http://dx.doi.org/10.1053/j.ajkd.2013.10.047] [PMID: 24461730]
[30]
Zakkerkish M, Shahbazian HB, Shahbazian H, Latifi SM, Moravej Aleali A. Albuminuria and its correlates in type 2 diabetic patients. Iran J Kidney Dis 2013; 7(4): 268-76.
[PMID: 23880803]
[31]
Perkins BA, Ficociello LH, Ostrander BE, et al. Microalbuminuria and the risk for early progressive renal function decline in type 1 diabetes. J Am Soc Nephrol 2007; 18(4): 1353-61.
[http://dx.doi.org/10.1681/ASN.2006080872] [PMID: 17329575]
[32]
Adler AI, Stevens RJ, Manley SE, Bilous RW, Cull CA, Holman RR. Development and progression of nephropathy in type 2 diabetes: The United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int 2003; 63(1): 225-32.
[http://dx.doi.org/10.1046/j.1523-1755.2003.00712.x] [PMID: 12472787]
[33]
Thomas MC, Brownlee M, Susztak K, et al. Diabetic kidney disease. Nat Rev Dis Primers 2015; 1: 15018.
[http://dx.doi.org/10.1038/nrdp.2015.18] [PMID: 27188921]
[34]
Pálsson R, Patel UD. Cardiovascular complications of diabetic kidney disease. Adv Chronic Kidney Dis 2014; 21(3): 273-80.
[http://dx.doi.org/10.1053/j.ackd.2014.03.003] [PMID: 24780455]
[35]
Gaede P. Intensive glucose control and cardiovascular disease in type 2 diabetes-should we change the recommended target for glycated hemoglobin? Commentary to ACCORD and ADVANCE trials. Pol Arch Med Wewn 2008; 118(11): 619-21.
[PMID: 19140564]
[36]
Sugahara M, Pak WLW. Update on diagnosis, pathophysiology, and management of diabetic kidney disease. Nephrology (Carlton) 2021; 26(6): 491-500.
[http://dx.doi.org/10.1111/nep.13860]
[37]
Coca SG, Ismail-Beigi F, Haq N, Krumholz HM, Parikh CR. Role of intensive glucose control in development of renal end points in type 2 diabetes mellitus: Systematic review and meta-analysis intensive glucose control in type 2 diabetes. Arch Intern Med 2012; 172(10): 761-9.
[http://dx.doi.org/10.1001/archinternmed.2011.2230] [PMID: 22636820]
[38]
Fullerton B, Jeitler K, Seitz M, Horvath K, Berghold A, Siebenhofer A. Intensive glucose control versus conventional glucose control for type 1 diabetes mellitus. Cochrane Database Syst Rev 2014; 2014(2): CD009122.
[http://dx.doi.org/10.1002/14651858.CD009122.pub2] [PMID: 24526393]
[39]
Emdin CA, Rahimi K, Neal B, Callender T, Perkovic V, Patel A. Blood pressure lowering in type 2 diabetes: A systematic review and meta-analysis. JAMA 2015; 313(6): 603-15.
[http://dx.doi.org/10.1001/jama.2014.18574] [PMID: 25668264]
[40]
Casas JP, Chua W, Loukogeorgakis S, et al. Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: Systematic review and meta-analysis. Lancet 2005; 366(9502): 2026-33.
[http://dx.doi.org/10.1016/S0140-6736(05)67814-2] [PMID: 16338452]
[41]
Tobe SW, Clase CM, Gao P, et al. Cardiovascular and renal outcomes with telmisartan, ramipril, or both in people at high renal risk: Results from the ONTARGET and TRANSCEND studies. Circulation 2011; 123(10): 1098-107.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.110.964171] [PMID: 21357827]
[42]
Bomback AS, Kshirsagar AV, Amamoo MA, Klemmer PJ. Change in proteinuria after adding aldosterone blockers to ACE inhibitors or angiotensin receptor blockers in CKD: A systematic review. Am J Kidney Dis 2008; 51(2): 199-211.
[http://dx.doi.org/10.1053/j.ajkd.2007.10.040] [PMID: 18215698]
[43]
Agarwal R. Effects of statins on renal function. Mayo Clin Proc 2007; 82(11): 1381-90.
[http://dx.doi.org/10.4065/82.11.1381] [PMID: 17976359]
[44]
Douglas K, O’Malley PG, Jackson JL. Meta-analysis: The effect of statins on albuminuria. Ann Intern Med 2006; 145(2): 117-24.
[http://dx.doi.org/10.7326/0003-4819-145-2-200607180-00009] [PMID: 16847294]
[45]
Pereira MJ, Eriksson JW. Emerging role of SGLT-2 inhibitors for the treatment of obesity. Drugs 2019; 79(3): 219-30.
[http://dx.doi.org/10.1007/s40265-019-1057-0] [PMID: 30701480]
[46]
Morales E, Valero MA, León M, Hernández E, Praga M. Beneficial effects of weight loss in overweight patients with chronic proteinuric nephropathies. Am J Kidney Dis 2003; 41(2): 319-27.
[http://dx.doi.org/10.1053/ajkd.2003.50039] [PMID: 12552492]
[47]
Tylicki L, Jakubowska A, Lizakowski S, Świetlik D, Rutkowski B. Management of renin-angiotensin system blockade in patients with chronic kidney disease under specialist care. Retrospective cross-sectional study. J Renin Angiotensin Aldosterone Syst 2015; 16(1): 145-52.
[http://dx.doi.org/10.1177/1470320314550018] [PMID: 25324423]
[48]
Rossing K, Schjoedt KJ, Smidt UM, Boomsma F, Parving HH. Beneficial effects of adding spironolactone to recommended antihypertensive treatment in diabetic nephropathy: A randomized, double-masked, cross-over study. Diabetes Care 2005; 28(9): 2106-12.
[http://dx.doi.org/10.2337/diacare.28.9.2106] [PMID: 16123474]
[49]
van den Meiracker AH, Baggen RG, Pauli S, et al. Spironolactone in type 2 diabetic nephropathy: Effects on proteinuria, blood pressure and renal function. J Hypertens 2006; 24(11): 2285-92.
[http://dx.doi.org/10.1097/01.hjh.0000249708.44016.5c] [PMID: 17053552]
[50]
Kolkhof P, Hartmann E, Freyberger A, et al. Effects of finerenone combined with empagliflozin in a model of hypertension-induced end-organ damage. Am J Nephrol 2021; 52(8): 642-52.
[http://dx.doi.org/10.1159/000516213] [PMID: 34111864]
[51]
Doria A, Niewczas MA, Fiorina P. Can existing drugs approved for other indications retard renal function decline in patients with type 1 diabetes and nephropathy? Semin Nephrol 2012; 32(5): 437-44.
[http://dx.doi.org/10.1016/j.semnephrol.2012.07.006] [PMID: 23062984]
[52]
Yin DD, Luo JH, Zhao ZY, Liao YJ, Li Y. Tranilast prevents renal interstitial fibrosis by blocking mast cell infiltration in a rat model of diabetic kidney disease. Mol Med Rep 2018; 17(5): 7356-64.
[http://dx.doi.org/10.3892/mmr.2018.8776] [PMID: 29568954]
[53]
Trachtman H, Fervenza FC, Gipson DS, et al. A phase 1, single-dose study of fresolimumab, an anti-TGF-β antibody, in treatment-resistant primary focal segmental glomerulosclerosis. Kidney Int 2011; 79(11): 1236-43.
[http://dx.doi.org/10.1038/ki.2011.33] [PMID: 21368745]
[54]
Moreno JA, Moreno S, Rubio-Navarro A, et al. Targeting chemokines in proteinuria-induced renal disease. Expert Opin Ther Targets 2012; 16(8): 833-45.
[http://dx.doi.org/10.1517/14728222.2012.703657] [PMID: 22793382]
[55]
Sullivan T, Miao Z, Dairaghi DJ, et al. CCR2 antagonist CCX140-B provides renal and glycemic benefits in diabetic transgenic human CCR2 knockin mice. Am J Physiol Renal Physiol 2013; 305(9): F1288-97.
[http://dx.doi.org/10.1152/ajprenal.00316.2013] [PMID: 23986513]
[56]
Raina R, Chauvin A, Chakraborty R, et al. The role of endothelin and endothelin antagonists in chronic kidney disease. Kidney Dis 2020; 6(1): 22-34.
[http://dx.doi.org/10.1159/000504623] [PMID: 32021871]
[57]
Enevoldsen FC, Sahana J, Wehland M, Grimm D, Infanger M, Krüger M. Endothelin receptor antagonists: Status quo and future perspectives for targeted therapy. J Clin Med 2020; 9(3): 824.
[http://dx.doi.org/10.3390/jcm9030824] [PMID: 32197449]
[58]
Ruiz-Ortega M, Rayego-Mateos S, Lamas S, Ortiz A, Rodrigues-Diez RR. Targeting the progression of chronic kidney disease. Nat Rev Nephrol 2020; 16(5): 269-88.
[http://dx.doi.org/10.1038/s41581-019-0248-y] [PMID: 32060481]
[59]
Balogh D, Hodrea J, Hosszu A, et al. MO620 antifibrotic effects of SGLT2 inhibition in the kidney and proximal tubular cells. Nephrol Dial Transplant 2021; 36(Supplement_1): gfab093.001.
[60]
Kawanami D, Takashi Y, Takahashi H, Motonaga R, Tanabe M. Renoprotective effects of DPP-4 inhibitors. Antioxidants 2021; 10(2): 246.
[http://dx.doi.org/10.3390/antiox10020246] [PMID: 33562528]
[61]
Galuška D, Pácal L. Kaňková K. Pathophysiological implication of vitamin D in diabetic kidney disease. Kidney Blood Press Res 2021; 46(2): 152-61.
[http://dx.doi.org/10.1159/000514286] [PMID: 33756482]
[62]
Gruson D, Rousseau MF, Ketelslegers JM, Hermans MP. Raised plasma urotensin II in type 2 diabetes patients is associated with the metabolic syndrome phenotype. J Clin Hypertens (Greenwich) 2010; 12(8): 653-60.
[http://dx.doi.org/10.1111/j.1751-7176.2010.00336.x] [PMID: 20695946]
[63]
Ozoux M-L, Briand V, Pelat M, et al. Potential therapeutic value of urotensin II receptor antagonist in chronic kidney disease and associated comorbidities. J Pharmacol Exp Ther 2020; 374(1): 24-37.
[http://dx.doi.org/10.1124/jpet.120.265496] [PMID: 32332113]
[64]
Gorin Y, Cavaglieri RC, Khazim K, et al. Targeting NADPH oxidase with a novel dual Nox1/Nox4 inhibitor attenuates renal pathology in type 1 diabetes. Am J Physiol Renal Physiol 2015; 308(11): F1276-87.
[http://dx.doi.org/10.1152/ajprenal.00396.2014] [PMID: 25656366]
[65]
Kwon G, Uddin MJ, Lee G, et al. A novel pan-Nox inhibitor, APX-115, protects kidney injury in streptozotocin-induced diabetic mice: Possible role of peroxisomal and mitochondrial biogenesis. Oncotarget 2017; 8(43): 74217-32.
[http://dx.doi.org/10.18632/oncotarget.18540] [PMID: 29088780]
[66]
Cui W, Min X, Xu X, Du B, Luo P. Role of nuclear factor erythroid 2-related factor 2 in diabetic nephropathy. J Diabetes Res 2017; 2017: 3797802.
[http://dx.doi.org/10.1155/2017/3797802] [PMID: 28512642]
[67]
Kanda H, Yamawaki K. Bardoxolone methyl: Drug development for diabetic kidney disease. J Clin Exp Nephrol 2020; 24(10): 857-64.
[http://dx.doi.org/10.1007/s10157-020-01917-5] [PMID: 32594372]
[68]
Kale A, Sankrityayan H, Anders H-J, Gaikwad AB. Epigenetic and non-epigenetic regulation of Klotho in kidney disease. Life Sci 2021; 264: 118644.
[http://dx.doi.org/10.1016/j.lfs.2020.118644] [PMID: 33141039]
[69]
Nascimento LRD, Domingueti CP. MicroRNAs: New biomarkers and promising therapeutic targets for diabetic kidney disease. J Bras Nefrol 2019; 41(3): 412-22.
[http://dx.doi.org/10.1590/2175-8239-jbn-2018-0165] [PMID: 30742700]
[70]
Zhu X, Zhang C, Fan Q, et al. Inhibiting microRNA-503 and microRNA-181d with losartan ameliorates diabetic nephropathy in KKAy mice. Med Sci Monit 2016; 22: 3902-9.
[http://dx.doi.org/10.12659/MSM.900938] [PMID: 27770539]
[71]
Xu XH, Ding DF, Yong HJ, et al. Resveratrol transcriptionally regulates miRNA-18a-5p expression ameliorating diabetic nephropathy via increasing autophagy. Eur Rev Med Pharmacol Sci 2017; 21(21): 4952-65.
[PMID: 29164562]
[72]
Han F, Wang S, Chang Y, et al. Triptolide prevents extracellular matrix accumulation in experimental diabetic kidney disease by targeting microRNA‐137/Notch1 pathway. J of Cel Phyysiol 2018; 233(3): 2225-37.
[73]
Kölling M, Kaucsar T, Schauerte C, et al. Therapeutic miR-21 silencing ameliorates diabetic kidney disease in mice. Mol Ther 2017; 25(1): 165-80.
[http://dx.doi.org/10.1016/j.ymthe.2016.08.001] [PMID: 28129112]
[74]
Matheus ASMM, Tannus LRM, Cobas RA, Palma CCS, Negrato CA, Gomes MB. Impact of diabetes on cardiovascular disease: An update. Int J Hypertens 2013; 2013: 653789.
[75]
Leon BM, Maddox TM. Diabetes and cardiovascular disease: Epidemiology, biological mechanisms, treatment recommendations and future research. World J Diabetes 2015; 6(13): 1246-58.
[http://dx.doi.org/10.4239/wjd.v6.i13.1246] [PMID: 26468341]
[76]
Ormazabal V, Nair S, Elfeky O, Aguayo C, Salomon C, Zuñiga FA. Association between insulin resistance and the development of cardiovascular disease. Cardiovasc Diabetol 2018; 17(1): 122.
[http://dx.doi.org/10.1186/s12933-018-0762-4] [PMID: 30170598]
[77]
Duncan BB, Schmidt MI, Pankow JS, et al. Low-grade systemic inflammation and the development of type 2 diabetes: The atherosclerosis risk in communities study. Diabetes 2003; 52(7): 1799-805.
[http://dx.doi.org/10.2337/diabetes.52.7.1799] [PMID: 12829649]
[78]
Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest 2006; 116(7): 1793-801.
[http://dx.doi.org/10.1172/JCI29069] [PMID: 16823477]
[79]
Kim M, Oh JK, Sakata S, et al. Role of resistin in cardiac contractility and hypertrophy. J Mol Cell Cardiol 2008; 45(2): 270-80.
[http://dx.doi.org/10.1016/j.yjmcc.2008.05.006] [PMID: 18597775]
[80]
Rogoveanu O-C, Mogoşanu GD, Bejenaru C, et al. Effects of calcium fructoborate on levels of C-reactive protein, total cholesterol, low-density lipoprotein, triglycerides, IL-1β IL-6, and MCP-1: A double-blind, placebo-controlled clinical study. Biol Trace Elem Res 2015; 163(1-2): 124-31.
[http://dx.doi.org/10.1007/s12011-014-0155-9] [PMID: 25433580]
[81]
Malek V, Sharma N, Sankrityayan H, Gaikwad AB. Concurrent neprilysin inhibition and renin-angiotensin system modulations prevented diabetic nephropathy. Life Sci 2019; 221: 159-67.
[http://dx.doi.org/10.1016/j.lfs.2019.02.027] [PMID: 30769114]
[82]
Mohamadshahi M, Veissi M, Haidari F, Javid AZ, Mohammadi F, Shirbeigi E. Effects of probiotic yogurt consumption on lipid profile in type 2 diabetic patients: A randomized controlled clinical trial. J Res Med Sci 2014; 19(6): 531-6.
[PMID: 25197295]
[83]
Prince CT, Secrest AM, Mackey RH, Arena VC, Kingsley LA, Orchard TJ. Cardiovascular autonomic neuropathy, HDL cholesterol, and smoking correlate with arterial stiffness markers determined 18 years later in type 1 diabetes. Diabetes Care 2010; 33(3): 652-7.
[http://dx.doi.org/10.2337/dc09-1936] [PMID: 20040653]
[84]
Fiodorenko-Dumas Ż, Dumas I, Mastej K, et al. Receptor GP IIb/IIIa as an indicator of risk in vascular events. Clin Appl Thromb Hemost 2019; 25: 1076029619845056.
[http://dx.doi.org/10.1177/1076029619845056] [PMID: 31185733]
[85]
Addai-Mensah O, Annani-Akollor ME, Nsafoah FO, et al. Effect of poor glycaemic control on plasma levels and activity of protein C, protein S, and antithrombin III in type 2 diabetes mellitus. PLoS One 2019; 14(9): e0223171.
[http://dx.doi.org/10.1371/journal.pone.0223171]
[86]
Vinik AI, Ziegler D. Diabetic cardiovascular autonomic neuropathy. Circulation 2007; 115(3): 387-97.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.634949] [PMID: 17242296]
[87]
Asghar O, Al-Sunni A, Khavandi K, et al. Diabetic cardiomyopathy. Clin Sci (Lond) 2009; 116(10): 741-60.
[http://dx.doi.org/10.1042/CS20080500] [PMID: 19364331]
[88]
Tribouilloy C, Rusinaru D, Mahjoub H, et al. Prognostic impact of diabetes mellitus in patients with heart failure and preserved ejection fraction: A prospective five-year study. Heart 2008; 94(11): 1450-5.
[http://dx.doi.org/10.1136/hrt.2007.128769] [PMID: 18208832]
[89]
Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology 2007; 132(6): 2131-57.
[http://dx.doi.org/10.1053/j.gastro.2007.03.054] [PMID: 17498508]
[90]
Drucker DJ. The biology of incretin hormones. Cell Metab 2006; 3(3): 153-65.
[http://dx.doi.org/10.1016/j.cmet.2006.01.004] [PMID: 16517403]
[91]
Deng X, Tavallaie MS, Sun R, et al. Drug discovery approaches targeting the incretin pathway. Bioorg Chem 2020; 99: 103810.
[http://dx.doi.org/10.1016/j.bioorg.2020.103810] [PMID: 32325333]
[92]
Brown E, Heerspink HJL, Cuthbertson DJ, Wilding JPH. SGLT2 inhibitors and GLP-1 receptor agonists: Established and emerging indications. Lancet 2021; 398(10296): 262-76.
[http://dx.doi.org/10.1016/S0140-6736(21)00536-5] [PMID: 34216571]
[93]
Standl E, Schnell O, McGuire DK, Ceriello A, Rydén L. Integration of recent evidence into management of patients with atherosclerotic cardiovascular disease and type 2 diabetes. Lancet Diabetes Endocrinol 2017; 5(5): 391-402.
[http://dx.doi.org/10.1016/S2213-8587(17)30033-5] [PMID: 28131656]
[94]
Wronkowitz N, Görgens SW, Romacho T, et al. Soluble DPP4 induces inflammation and proliferation of human smooth muscle cells via protease-activated receptor 2. Biochim Biophys Acta 2014; 1842(9): 1613-21.
[http://dx.doi.org/10.1016/j.bbadis.2014.06.004] [PMID: 24928308]
[95]
Chihara A, Tanaka A, Morimoto T, et al. Differences in lipid metabolism between anagliptin and sitagliptin in patients with type 2 diabetes on statin therapy: A secondary analysis of the REASON trial. Cardiovasc Diabetol 2019; 18(1): 158.
[http://dx.doi.org/10.1186/s12933-019-0965-3] [PMID: 31733647]
[96]
Watanabe A, Choe S, Chaptal V, et al. The mechanism of sodium and substrate release from the binding pocket of vSGLT. Nature 2010; 468(7326): 988-91.
[http://dx.doi.org/10.1038/nature09580] [PMID: 21131949]
[97]
Ferrannini E, Muscelli E, Frascerra S, et al. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest 2014; 124(2): 499-508.
[http://dx.doi.org/10.1172/JCI72227] [PMID: 24463454]
[98]
Bonner C, Kerr-Conte J, Gmyr V, et al. Inhibition of the glucose transporter SGLT2 with dapagliflozin in pancreatic alpha cells triggers glucagon secretion. Nat Med 2015; 21(5): 512-7.
[http://dx.doi.org/10.1038/nm.3828] [PMID: 25894829]
[99]
Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373(22): 2117-28.
[http://dx.doi.org/10.1056/NEJMoa1504720] [PMID: 26378978]
[100]
Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019; 380(4): 347-57.
[http://dx.doi.org/10.1056/NEJMoa1812389] [PMID: 30415602]
[101]
Cannon CP, Pratley R, Dagogo-Jack S, et al. Cardiovascular outcomes with ertugliflozin in type 2 diabetes. N Engl J Med 2020; 383(15): 1425-35.
[http://dx.doi.org/10.1056/NEJMoa2004967] [PMID: 32966714]
[102]
Bhatt DL, Szarek M, Pitt B, et al. Sotagliflozin in patients with diabetes and chronic kidney disease. N Engl J Med 2021; 384(2): 129-39.
[http://dx.doi.org/10.1056/NEJMoa2030186] [PMID: 33200891]
[103]
Bhatt DL, Szarek M, Steg PG, et al. Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med 2021; 384(2): 117-28.
[http://dx.doi.org/10.1056/NEJMoa2030183] [PMID: 33200892]
[104]
Seidah NG, Awan Z, Chrétien M, Mbikay M. PCSK9: A key modulator of cardiovascular health. Circ Res 2014; 114(6): 1022-36.
[http://dx.doi.org/10.1161/CIRCRESAHA.114.301621] [PMID: 24625727]
[105]
Vaduganathan M, Claggett BL, Jhund PS, et al. Estimating lifetime benefits of comprehensive disease-modifying pharmacological therapies in patients with heart failure with reduced ejection fraction: A comparative analysis of three randomised controlled trials. Lancet 2020; 396(10244): 121-8.
[http://dx.doi.org/10.1016/S0140-6736(20)30748-0] [PMID: 32446323]
[106]
Kühnast S, van der Hoorn JWA, Pieterman EJ, et al. Alirocumab inhibits atherosclerosis, improves the plaque morphology, and enhances the effects of a statin. J Lipid Res 2014; 55(10): 2103-12.
[http://dx.doi.org/10.1194/jlr.M051326] [PMID: 25139399]
[107]
Chan JC, Piper DE, Cao Q, et al. A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates. Proc Natl Acad Sci USA 2009; 106(24): 9820-5.
[http://dx.doi.org/10.1073/pnas.0903849106] [PMID: 19443683]
[108]
Warden BA, Fazio S, Shapiro MD. The PCSK9 revolution: Current status, controversies, and future directions. Trends Cardiovasc Med 2020; 30(3): 179-85.
[http://dx.doi.org/10.1016/j.tcm.2019.05.007] [PMID: 31151804]
[109]
Blanchard V, Khantalin I, Ramin-Mangata S, Chémello K, Nativel B, Lambert G. PCSK9: From biology to clinical applications. Pathology 2019; 51(2): 177-83.
[http://dx.doi.org/10.1016/j.pathol.2018.10.012] [PMID: 30522786]

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