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Current Diabetes Reviews

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

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Mini-Review Article

Diabetes and Its Complications: Therapies Available, Anticipated and Aspired

Author(s): Anu Grover*, Komal Sharma, Suresh Gautam, Srishti Gautam, Monica Gulati and Sachin Kumar Singh

Volume 17, Issue 4, 2021

Published on: 03 November, 2020

Page: [397 - 420] Pages: 24

DOI: 10.2174/1573399816666201103144231

Price: $65

Abstract

Worldwide, diabetes ranks among the ten leading causes of mortality. Prevalence of diabetes is growing rapidly in low and middle income countries. It is a progressive disease leading to serious co-morbidities, which results in increased cost of treatment and over-all health system of the country. Pathophysiological alterations in Type 2 Diabetes (T2D) progressed from a simple disturbance in the functioning of the pancreas to triumvirate to ominous octet to egregious eleven to dirty dozen model. Due to complex interplay of multiple hormones in T2D, there may be multifaceted approach in its management. The ‘long-term secondary complications’ in uncontrolled diabetes may affect almost every organ of the body, and finally may lead to multi-organ dysfunction. Available therapies are inconsistent in maintaining long term glycemic control and their long term use may be associated with adverse effects. There is need for newer drugs, not only for glycemic control but also for prevention or mitigation of secondary microvascular and macrovascular complications. Increased knowledge of the pathophysiology of diabetes has contributed to the development of novel treatments. Several new agents like Glucagon Like Peptide - 1 (GLP-1) agonists, Dipeptidyl Peptidase IV (DPP-4) inhibitors, amylin analogues, Sodium-Glucose transport -2 (SGLT- 2) inhibitors and dual Peroxisome Proliferator-Activated Receptor (PPAR) agonists are available or will be available soon, thus extending the range of therapy for T2D, thereby preventing its long term complications. The article discusses the pathophysiology of diabetes along with its comorbidities, with a focus on existing and novel upcoming antidiabetic drugs which are under investigation. It also dives deep to deliberate upon the novel therapies that are in various stages of development. Adding new options with new mechanisms of action to the treatment armamentarium of diabetes may eventually help improve outcomes and reduce its economic burden.

Keywords: Type 2 Diabetes, Pathophysiology, Diabetic complications, Management of T2D, Cardioprotection, GLP-1.

[1]
International Diabetes Federation IDF diabetes atlas. 9th ed. 2019.
[2]
Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition.Diabetes Res Clin Pract. 2019. 157: 107843.
[3]
Anjana RM, Deepa M, Pradeepa R, et al. ICMR–INDIAB Collaborative Study Group. Prevalence of diabetes and prediabetes in 15 states of India: results from the ICMR-INDIAB population-based cross-sectional study. Lancet Diabetes Endocrinol 2017; 5(8): 585-96. [published correction appears in Lancet Diabetes Endocrinol. 2017 Aug;5(8):e5].
[http://dx.doi.org/10.1016/S2213-8587(17)30174-2] [PMID: 28601585]
[4]
https://www.who.int/publications/i/item/who-ucn-ncd-20.1
[5]
Tenenbaum A, Fisman EZ, Motro M. Metabolic syndrome and type 2 diabetes mellitus: focus on peroxisome proliferator activated receptors (PPAR). Cardiovasc Diabetol 2003; 2: 4.
[http://dx.doi.org/10.1186/1475-2840-2-4] [PMID: 12834541]
[6]
Iglay K, Hannachi H, Joseph Howie P, et al. Prevalence and co-prevalence of comorbidities among patients with type 2 diabetes mellitus. Curr Med Res Opin 2016; 32(7): 1243-52.
[http://dx.doi.org/10.1185/03007995.2016.1168291] [PMID: 26986190]
[7]
Waeber B, Feihl F, Ruilope L. Diabetes and hypertension. Blood Press 2001; 10(5-6): 311-21.
[http://dx.doi.org/10.1080/080370501753400610] [PMID: 11822535]
[8]
Forbes JM, Fotheringham AK. Vascular complications in diabetes: old messages, new thoughts. Diabetologia 2017; 60(11): 2129-38.
[http://dx.doi.org/10.1007/s00125-017-4360-x] [PMID: 28725914]
[9]
United States Renal Data System. International comparisons.United States Renal Data System 2014 USRDS annual data report: epidemiology of kidney disease in the United States. Bethesda: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases 2014.
[10]
Pouwer F. Depression: A common and burdensome complication of diabetes that warrants the continued attention of clinicians, researchers and healthcare policy makers. Diabetologia 2017; 60(1): 30-4.
[http://dx.doi.org/10.1007/s00125-016-4154-6] [PMID: 27838735]
[11]
Vondra K, Vrbikova J, Dvorakova K. Thyroid gland diseases in adult patients with diabetes mellitus. Minerva Endocrinol 2005; 30(4): 217-36.
[PMID: 16319810]
[12]
Feary JR, Rodrigues LC, Smith CJ, Hubbard RB, Gibson JE. Prevalence of major comorbidities in subjects with COPD and incidence of myocardial infarction and stroke: a comprehensive analysis using data from primary care. Thorax 2010; 65(11): 956-62.
[http://dx.doi.org/10.1136/thx.2009.128082] [PMID: 20871122]
[13]
Rahaman K, Reza M, Kourosh N, et al. Comorbidities and care practices of diabetic patients. Austin J Public Health and Epidemiol 2017; 4: 1059-61.
[14]
Eller-Vainicher C, Cairoli E, Grassi G, et al. Pathophysiology and management of type 2 diabetes mellitus bone fragility. J Diabetes Res 2020; 2020: 7608964.
[http://dx.doi.org/10.1155/2020/7608964] [PMID: 32566682]
[15]
Thanopoulou A, Pectasides D. Real life cancer comorbidity in Greek patients with diabetes mellitus followed up at a single diabetes center: an unappreciated new diabetes complication. J Diabetes Res 2014; 2014: 231425.
[http://dx.doi.org/10.1155/2014/231425] [PMID: 25136643]
[16]
Nowakowska M, Zghebi SS, Ashcroft DM, et al. The comorbidity burden of type 2 diabetes mellitus: patterns, clusters and predictions from a large English primary care cohort. BMC Med 2019; 17(1): 145. [published correction appears in BMC Med. 2020 Jan 25;18(1):22].
[http://dx.doi.org/10.1186/s12916-019-1373-y] [PMID: 31345214]
[17]
Himsworth HP. Diabetes mellitus: its differentiation into insulin-sensitive and insulin-insensitive types. 1936. Int J Epidemiol 2013; 42(6): 1594-8.
[http://dx.doi.org/10.1093/ije/dyt203] [PMID: 24415598]
[18]
Brunton S. Pathophysiology of Type 2 Diabetes: The Evolution of Our Understanding. J Fam Pract 2016.
[19]
Kahn SE, Cooper ME, Del Prato S. Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future. Lancet 2014; 383(9922): 1068-83.
[http://dx.doi.org/10.1016/S0140-6736(13)62154-6] [PMID: 24315620]
[20]
DeFronzo RA. Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 1988; 37(6): 667-87.
[http://dx.doi.org/10.2337/diab.37.6.667] [PMID: 3289989]
[21]
Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 2009; 58(4): 773-95.
[http://dx.doi.org/10.2337/db09-9028] [PMID: 19336687]
[22]
Schwartz SS, Epstein S, Corkey BE, Grant SF, Gavin JR III, Aguilar RB. The Time Is Right for a New Classification System for Diabetes: Rationale and Implications of the β-Cell-Centric Classification Schema. Diabetes Care 2016; 39(2): 179-86.
[http://dx.doi.org/10.2337/dc15-1585] [PMID: 26798148]
[23]
Kalra S, Chawla R, Madhu SV. The dirty dozen of diabetes. Indian J Endocrinol Metab 2013; 17(3): 367-9.
[http://dx.doi.org/10.4103/2230-8210.111593] [PMID: 23869290]
[24]
Somasundaram NP, Wijesinghe AM. Therapy for type 2 diabetes mellitus: targeting the ‘Unlucky Thirteen’. Jacobs J Diabetes Endocrinol 2016; 2(1): 12.
[25]
Prabhakar P. Pathophysiology of secondary complications of diabetes mellitus. Asian J Pharm Clinic Res 2016; 9(1): 23-7.
[26]
Kitada M, Zhang Z, Mima A, King GL. Molecular mechanisms of diabetic vascular complications. J Diabetes Investig 2010; 1(3): 77-89.
[http://dx.doi.org/10.1111/j.2040-1124.2010.00018.x] [PMID: 24843412]
[27]
Lorenzi M. The polyol pathway as a mechanism for diabetic retinopathy: attractive, elusive, and resilient. Exp Diabetes Res 2007; 2007: 61038.
[http://dx.doi.org/10.1155/2007/61038] [PMID: 18224243]
[28]
Chait A, Bornfeldt KE. Diabetes and atherosclerosis: is there a role for hyperglycemia? J Lipid Res 2009; 50: 335-9.
[29]
Tesfamariam B. Free radicals in diabetic endothelial cell dysfunction. Free Radic Biol Med 1994; 16(3): 383-91.
[http://dx.doi.org/10.1016/0891-5849(94)90040-X] [PMID: 8063201]
[30]
Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001; 414(6865): 813-20.
[http://dx.doi.org/10.1038/414813a] [PMID: 11742414]
[31]
Uribarri J, Peppa M, Cai W, et al. Restriction of dietary glycotoxins reduces excessive advanced glycation end products in renal failure patients. J Am Soc Nephrol 2003; 14(3): 728-31.
[http://dx.doi.org/10.1097/01.ASN.0000051593.41395.B9] [PMID: 12595509]
[32]
Haitoglou CS, Tsilibary EC, Brownlee M, Charonis AS. Altered cellular interactions between endothelial cells and nonenzymatically glucosylated laminin/type IV collagen. J Biol Chem 1992; 267(18): 12404-7.
[PMID: 1618745]
[33]
Schalkwijk CG, Stehouwer CD. Vascular complications in diabetes mellitus: the role of endothelial dysfunction. Clin Sci (Lond) 2005; 109(2): 143-59.
[http://dx.doi.org/10.1042/CS20050025] [PMID: 16033329]
[34]
Stitt AW. The role of advanced glycation in the pathogenesis of diabetic retinopathy. Exp Mol Pathol 2003; 75(1): 95-108.
[http://dx.doi.org/10.1016/S0014-4800(03)00035-2] [PMID: 12834631]
[35]
Chen CY, Abell AM, Moon YS, Kim KH. An advanced glycation end product (AGE)-receptor for AGEs (RAGE) axis restores adipogenic potential of senescent preadipocytes through modulation of p53 protein function. J Biol Chem 2012; 287(53): 44498-507. [published correction appears in J Biol Chem. 2013 Apr 12;288(15):10949]. [published correction appears in J Biol Chem. 2014 Apr 18;289(16):11570].
[http://dx.doi.org/10.1074/jbc.M112.399790] [PMID: 23150674]
[36]
Brownlee M. Lilly Lecture 1993. Glycation and diabetic complications. Diabetes 1994; 43(6): 836-41.
[http://dx.doi.org/10.2337/diab.43.6.836] [PMID: 8194672]
[37]
Horal M, Zhang Z, Stanton R, Virkamäki A, Loeken MR. Activation of the hexosamine pathway causes oxidative stress and abnormal embryo gene expression: involvement in diabetic teratogenesis. Birth Defects Res A Clin Mol Teratol 2004; 70(8): 519-27.
[http://dx.doi.org/10.1002/bdra.20056] [PMID: 15329829]
[38]
Koya D, King GL. Protein kinase C activation and the development of diabetic complications. Diabetes 1998; 47(6): 859-66.
[http://dx.doi.org/10.2337/diabetes.47.6.859] [PMID: 9604860]
[39]
Inoguchi T, Battan R, Handler E, Sportsman JR, Heath W, King GL. Preferential elevation of protein kinase C isoform beta II and diacylglycerol levels in the aorta and heart of diabetic rats: differential reversibility to glycemic control by islet cell transplantation. Proc Natl Acad Sci USA 1992; 89(22): 11059-63.
[http://dx.doi.org/10.1073/pnas.89.22.11059] [PMID: 1438315]
[40]
Feener EP, Xia P, Inoguchi T, Shiba T, Kunisaki M, King GL. Role of protein kinase C in glucose- and angiotensin II-induced plasminogen activator inhibitor expression. Contrib Nephrol 1996; 118: 180-7.
[http://dx.doi.org/10.1159/000425092] [PMID: 8744056]
[41]
Suryavanshi SV, Kulkarni YA. NF-κβ: A Potential Target in the Management of Vascular Complications of Diabetes. Front Pharmacol 2017; 8: 798.
[http://dx.doi.org/10.3389/fphar.2017.00798] [PMID: 29163178]
[42]
Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res 2010; 107(9): 1058-70.
[http://dx.doi.org/10.1161/CIRCRESAHA.110.223545] [PMID: 21030723]
[43]
Forbes JM, Coughlan MT, Cooper ME. Oxidative stress as a major culprit in kidney disease in diabetes. Diabetes 2008; 57(6): 1446-54.
[http://dx.doi.org/10.2337/db08-0057] [PMID: 18511445]
[44]
Nishikawa T, Edelstein D, Du XL, et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 2000; 404(6779): 787-90.
[http://dx.doi.org/10.1038/35008121] [PMID: 10783895]
[45]
Schrauwen P, Hesselink MK. Oxidative capacity, lipotoxicity, and mitochondrial damage in type 2 diabetes. Diabetes 2004; 53(6): 1412-7.
[http://dx.doi.org/10.2337/diabetes.53.6.1412] [PMID: 15161742]
[46]
Du Y, Miller CM, Kern TS. Hyperglycemia increases mitochondrial superoxide in retina and retinal cells. Free Radic Biol Med 2003; 35(11): 1491-9.
[http://dx.doi.org/10.1016/j.freeradbiomed.2003.08.018] [PMID: 14642397]
[47]
Nishikawa T, Sasahara T, Kiritoshi S, et al. Evaluation of urinary 8-hydroxydeoxy-guanosine as a novel biomarker of macrovascular complications in type 2 diabetes. Diabetes Care 2003; 26(5): 1507-12.
[http://dx.doi.org/10.2337/diacare.26.5.1507] [PMID: 12716813]
[48]
Sifuentes-Franco S, Pacheco-Moisés FP, Rodríguez-Carrizalez AD, Miranda-Díaz AG. The Role of Oxidative Stress, Mitochondrial Function, and Autophagy in Diabetic Polyneuropathy. J Diabetes Res 2017; 2017: 1673081.
[http://dx.doi.org/10.1155/2017/1673081] [PMID: 29204450]
[49]
Mariotto S, Menegazzi M, Suzuki H. Biochemical aspects of nitric oxide. Curr Pharm Des 2004; 10(14): 1627-45.
[http://dx.doi.org/10.2174/1381612043384637] [PMID: 15134561]
[50]
West MB, Ramana KV, Kaiserova K, Srivastava SK, Bhatnagar A. L-Arginine prevents metabolic effects of high glucose in diabetic mice. FEBS Lett 2008; 582(17): 2609-14.
[http://dx.doi.org/10.1016/j.febslet.2008.06.039] [PMID: 18586034]
[51]
Sun J, Cui J, He Q, Chen Z, Arvan P, Liu M. Proinsulin misfolding and endoplasmic reticulum stress during the development and progression of diabetes. Mol Aspects Med 2015; 42: 105-18.
[http://dx.doi.org/10.1016/j.mam.2015.01.001] [PMID: 25579745]
[52]
Zeeshan HM, Lee GH, Kim HR, Chae HJ. Endoplasmic Reticulum Stress and Associated ROS. Int J Mol Sci 2016; 17(3): 327.
[http://dx.doi.org/10.3390/ijms17030327] [PMID: 26950115]
[53]
Malhotra JD, Kaufman RJ. Endoplasmic reticulum stress and oxidative stress: a vicious cycle or a double-edged sword? Antioxid Redox Signal 2007; 9(12): 2277-93.
[http://dx.doi.org/10.1089/ars.2007.1782] [PMID: 17979528]
[54]
Chow FY, Nikolic-Paterson DJ, Ma FY, Ozols E, Rollins BJ, Tesch GH. Monocyte chemoattractant protein-1-induced tissue inflammation is critical for the development of renal injury but not type 2 diabetes in obese db/db mice. Diabetologia 2007; 50(2): 471-80.
[http://dx.doi.org/10.1007/s00125-006-0497-8] [PMID: 17160673]
[55]
Téllez Gil L, Roselló AM, Collado Torres A, Moreno RL, Antonio Ferrón Orihuela J. Modulation of soluble phases of endothelial/leukocyte adhesion molecule 1, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 with interleukin-1beta after experimental endotoxic challenge. Crit Care Med 2001; 29(4): 776-81.
[http://dx.doi.org/10.1097/00003246-200104000-00018] [PMID: 11373468]
[56]
Pfeilschifter J, Mühl H. Interleukin 1 and tumor necrosis factor potentiate angiotensin II- and calcium ionophore-stimulated prostaglandin E2 synthesis in rat renal mesangial cells. Biochem Biophys Res Commun 1990; 169(2): 585-95.
[http://dx.doi.org/10.1016/0006-291X(90)90371-S] [PMID: 2113380]
[57]
Saraheimo M, Teppo AM, Forsblom C, Fagerudd J, Groop PH. Diabetic nephropathy is associated with low-grade inflammation in Type 1 diabetic patients. Diabetologia 2003; 46(10): 1402-7.
[http://dx.doi.org/10.1007/s00125-003-1194-5] [PMID: 12928771]
[58]
Doupis J, Lyons TE, Wu S, Gnardellis C, Dinh T, Veves A. Microvascular reactivity and inflammatory cytokines in painful and painless peripheral diabetic neuropathy. J Clin Endocrinol Metab 2009; 94(6): 2157-63.
[http://dx.doi.org/10.1210/jc.2008-2385] [PMID: 19276232]
[59]
Thompson D, Pepys MB, Wood SP. The physiological structure of human C-reactive protein and its complex with phosphocholine. Structure 1999; 7(2): 169-77.
[http://dx.doi.org/10.1016/S0969-2126(99)80023-9] [PMID: 10368284]
[60]
Park S, Kang HJ, Jeon JH, Kim MJ, Lee IK. Recent advances in the pathogenesis of microvascular complications in diabetes. Arch Pharm Res 2019; 42(3): 252-62.
[http://dx.doi.org/10.1007/s12272-019-01130-3] [PMID: 30771210]
[61]
Caramori ML, Fioretto P, Mauer M. The need for early predictors of diabetic nephropathy risk: is albumin excretion rate sufficient? Diabetes 2000; 49(9): 1399-408.
[http://dx.doi.org/10.2337/diabetes.49.9.1399] [PMID: 10969821]
[62]
Adler AI, Stevens RJ, Manley SE, Bilous RW, Cull CA, Holman RR. UKPDS GROUP. 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]
[63]
Gnudi L. Cellular and molecular mechanisms of diabetic glomerulopathy. Nephrol Dial Transplant 2012; 27(7): 2642-9.
[http://dx.doi.org/10.1093/ndt/gfs121] [PMID: 22584788]
[64]
Gnudi L, Karalliedde J. Beat it early: putative renoprotective haemodynamic effects of oral hypoglycaemic agents. Nephrol Dial Transplant 2016; 31(7): 1036-43.
[http://dx.doi.org/10.1093/ndt/gfv093] [PMID: 25858586]
[65]
Forbes JM, Cooper ME. Mechanisms of diabetic complications. Physiol Rev 2013; 93(1): 137-88.
[http://dx.doi.org/10.1152/physrev.00045.2011] [PMID: 23303908]
[66]
De Cosmo S, Menzaghi C, Prudente S, Trischitta V. Role of insulin resistance in kidney dysfunction: insights into the mechanism and epidemiological evidence. Nephrol Dial Transplant 2013; 28(1): 29-36.
[http://dx.doi.org/10.1093/ndt/gfs290] [PMID: 23048172]
[67]
Ruggenenti P, Cravedi P, Remuzzi G. The RAAS in the pathogenesis and treatment of diabetic nephropathy. Nat Rev Nephrol 2010; 6(6): 319-30.
[http://dx.doi.org/10.1038/nrneph.2010.58] [PMID: 20440277]
[68]
Bonnet F, Cooper ME, Kawachi H, Allen TJ, Boner G, Cao Z. Irbesartan normalises the deficiency in glomerular nephrin expression in a model of diabetes and hypertension. Diabetologia 2001; 44(7): 874-7.
[http://dx.doi.org/10.1007/s001250100546] [PMID: 11508272]
[69]
Tonneijck L, Muskiet MHA, Smits MM, et al. Postprandial renal haemodynamic effect of lixisenatide vs once-daily insulin-glulisine in patients with type 2 diabetes on insulin-glargine: An 8-week, randomised, open-label trial. Diabetes Obes Metab 2017; 19(12): 1669-80.
[http://dx.doi.org/10.1111/dom.12985] [PMID: 28449402]
[70]
Ruggenenti P, Porrini EL, Gaspari F, et al. GFR Study Investigators. Glomerular hyperfiltration and renal disease progression in type 2 diabetes. Diabetes Care 2012; 35(10): 2061-8.
[http://dx.doi.org/10.2337/dc11-2189] [PMID: 22773704]
[71]
Zheng Y, He M, Congdon N. The worldwide epidemic of diabetic retinopathy. Indian J Ophthalmol 2012; 60(5): 428-31.
[http://dx.doi.org/10.4103/0301-4738.100542] [PMID: 22944754]
[72]
Romeo G, Liu WH, Asnaghi V, Kern TS, Lorenzi M. Activation of nuclear factor-kappaB induced by diabetes and high glucose regulates a proapoptotic program in retinal pericytes. Diabetes 2002; 51(7): 2241-8.
[http://dx.doi.org/10.2337/diabetes.51.7.2241] [PMID: 12086956]
[73]
Wang W, Lo ACY. Diabetic Retinopathy: Pathophysiology and Treatments. Int J Mol Sci 2018; 19(6): 1816.
[http://dx.doi.org/10.3390/ijms19061816] [PMID: 29925789]
[74]
Huang H, He J, Johnson D, et al. Deletion of placental growth factor prevents diabetic retinopathy and is associated with Akt activation and HIF1α-VEGF pathway inhibition. diabetes 2015;64:200-212. Diabetes 2015; 64(3): 1067.
[http://dx.doi.org/10.2337/db15-er03] [PMID: 25713201]
[75]
Behl T, Kotwani A. Exploring the various aspects of the pathological role of Vascular Endothelial Growth Factor (VEGF) in diabetic retinopathy. Pharmacol Res 2015; 99: 137-48.
[http://dx.doi.org/10.1016/j.phrs.2015.05.013] [PMID: 26054568]
[76]
Abcouwer SF. Müller Cell-Microglia Cross Talk Drives Neuroinflammation in Diabetic Retinopathy. Diabetes 2017; 66(2): 261-3.
[http://dx.doi.org/10.2337/dbi16-0047] [PMID: 28108606]
[77]
Miyamoto K, Khosrof S, Bursell SE, et al. Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition. Proc Natl Acad Sci USA 1999; 96(19): 10836-41.
[http://dx.doi.org/10.1073/pnas.96.19.10836] [PMID: 10485912]
[78]
Yuuki T, Kanda T, Kimura Y, et al. Inflammatory cytokines in vitreous fluid and serum of patients with diabetic vitreoretinopathy. J Diabetes Complications 2001; 15(5): 257-9.
[http://dx.doi.org/10.1016/S1056-8727(01)00155-6] [PMID: 11522500]
[79]
Schröder S, Palinski W, Schmid-Schönbein GW. Activated monocytes and granulocytes, capillary nonperfusion, and neovascularization in diabetic retinopathy. Am J Pathol 1991; 139(1): 81-100.
[PMID: 1713023]
[80]
Joussen AM, Poulaki V, Mitsiades N, et al. Suppression of Fas- FasL-induced endothelial cell apoptosis prevents diabetic blood-retinal barrier breakdown in a model of streptozotocin-induced diabetes. FASEB J 2003; 17(1): 76-8.
[http://dx.doi.org/10.1096/fj.02-0157fje] [PMID: 12475915]
[81]
Hammes HP. Diabetic retinopathy: hyperglycaemia, oxidative stress and beyond. Diabetologia 2018; 61(1): 29-38.
[http://dx.doi.org/10.1007/s00125-017-4435-8] [PMID: 28942458]
[82]
Feldman EL, Callaghan BC, Pop-Busui R, et al. Diabetic neuropathy. Nat Rev Dis Primers 2019; 5(1): 41.
[http://dx.doi.org/10.1038/s41572-019-0092-1] [PMID: 31197153]
[83]
Feldman EL, Nave KA, Jensen TS, Bennett DLH. New Horizons in Diabetic Neuropathy: Mechanisms, Bioenergetics, and Pain. Neuron 2017; 93(6): 1296-313.
[http://dx.doi.org/10.1016/j.neuron.2017.02.005] [PMID: 28334605]
[84]
Callaghan BC, Gallagher G, Fridman V, Feldman EL. Diabetic neuropathy: what does the future hold? Diabetologia 2020; 63(5): 891-7.
[http://dx.doi.org/10.1007/s00125-020-05085-9] [PMID: 31974731]
[85]
Vincent AM, Brownlee M, Russell JW. Oxidative stress and programmed cell death in diabetic neuropathy. Ann N Y Acad Sci 2002; 959: 368-83.
[http://dx.doi.org/10.1111/j.1749-6632.2002.tb02108.x] [PMID: 11976211]
[86]
Haslbeck KM, Schleicher E, Bierhaus A, et al. The AGE/RAGE/NF-(kappa)B pathway may contribute to the pathogenesis of polyneuropathy in impaired glucose tolerance (IGT). Exp Clin Endocrinol Diabetes 2005; 113(5): 288-91.
[http://dx.doi.org/10.1055/s-2005-865600] [PMID: 15926115]
[87]
Okamoto K, Martin DP, Schmelzer JD, Mitsui Y, Low PA. Pro- and anti-inflammatory cytokine gene expression in rat sciatic nerve chronic constriction injury model of neuropathic pain. Exp Neurol 2001; 169(2): 386-91.
[http://dx.doi.org/10.1006/exnr.2001.7677] [PMID: 11358451]
[88]
Yagihashi S, Yamagishi S, Wada R. Pathology and pathogenetic mechanisms of diabetic neuropathy: correlation with clinical signs and symptoms. Diabetes Res Clin Pract 2007; 77(Suppl. 1): S184-9.
[http://dx.doi.org/10.1016/j.diabres.2007.01.054] [PMID: 17462777]
[89]
Obrosova IG. Diabetic painful and insensate neuropathy: pathogenesis and potential treatments. Neurotherapeutics 2009; 6(4): 638-47.
[http://dx.doi.org/10.1016/j.nurt.2009.07.004] [PMID: 19789069]
[90]
Bowes CD, Lien LF, Butler J. Clinical aspects of heart failure in individuals with diabetes. Diabetologia 2019; 62(9): 1529-38.
[http://dx.doi.org/10.1007/s00125-019-4958-2] [PMID: 31342083]
[91]
Ali MK, Narayan KM, Tandon N. Diabetes & coronary heart disease: current perspectives. Indian J Med Res 2010; 132(5): 584-97.
[PMID: 21150011]
[92]
Jia G, Whaley-Connell A, Sowers JR. Diabetic cardiomyopathy: a hyperglycaemia- and insulin-resistance-induced heart disease. Diabetologia 2018; 61(1): 21-8.
[http://dx.doi.org/10.1007/s00125-017-4390-4] [PMID: 28776083]
[93]
Bell DSH, Goncalves E. Atrial fibrillation and type 2 diabetes: Prevalence, etiology, pathophysiology and effect of anti-diabetic therapies. Diabetes Obes Metab 2019; 21(2): 210-7.
[http://dx.doi.org/10.1111/dom.13512] [PMID: 30144274]
[94]
Chen-Scarabelli C, Scarabelli TM. Suboptimal glycemic control, independently of QT interval duration, is associated with increased risk of ventricular arrhythmias in a high-risk population. Pacing Clin Electrophysiol 2006; 29(1): 9-14.
[http://dx.doi.org/10.1111/j.1540-8159.2006.00298.x] [PMID: 16441711]
[95]
Dhananjayan R, Koundinya KS, Malati T, Kutala VK. Endothelial Dysfunction in Type 2 Diabetes Mellitus. Indian J Clin Biochem 2016; 31(4): 372-9.
[http://dx.doi.org/10.1007/s12291-015-0516-y] [PMID: 27605734]
[96]
Tabit CE, Chung WB, Hamburg NM, Vita JA. Endothelial dysfunction in diabetes mellitus: molecular mechanisms and clinical implications. Rev Endocr Metab Disord 2010; 11(1): 61-74.
[http://dx.doi.org/10.1007/s11154-010-9134-4] [PMID: 20186491]
[97]
Westermeier F, Riquelme JA, Pavez M, et al. New Molecular Insights of Insulin in Diabetic Cardiomyopathy. Front Physiol 2016; 7: 125.
[http://dx.doi.org/10.3389/fphys.2016.00125] [PMID: 27148064]
[98]
Ramachandra CJA, Ja KPMM, Chua J, Cong S, Shim W, Hausenloy DJ. Myeloperoxidase As a Multifaceted Target for Cardiovascular Protection. Antioxid Redox Signal 2020; 32(15): 1135-49.
[http://dx.doi.org/10.1089/ars.2019.7971] [PMID: 31847538]
[99]
Marshall SM. 60 years of metformin use: a glance at the past and a look to the future. Diabetologia 2017; 60(9): 1561-5.
[http://dx.doi.org/10.1007/s00125-017-4343-y] [PMID: 28776085]
[100]
Lane W, Weinrib S, Rappaport J, Hale C. The effect of addition of liraglutide to high-dose intensive insulin therapy: A randomized prospective trial. Diabetes Obes Metab 2014; 16(9): 827-32.
[http://dx.doi.org/10.1111/dom.12286] [PMID: 24589127]
[101]
Bolen S, Feldman L, Vassy J, et al. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med 2007; 147(6): 386-99. [published correction appears in Ann Intern Med. 2007 Dec 18;147(12):887].
[http://dx.doi.org/10.7326/0003-4819-147-6-200709180-00178] [PMID: 17638715]
[102]
Holstein A, Stumvoll M. Contraindications can damage your health-is metformin a case in point? Diabetologia 2005; 48(12): 2454-9.
[http://dx.doi.org/10.1007/s00125-005-0026-1] [PMID: 16283245]
[103]
Nicholson G, Hall GM. Diabetes mellitus: new drugs for a new epidemic. Br J Anaesth 2011; 107(1): 65-73.
[http://dx.doi.org/10.1093/bja/aer120] [PMID: 21610015]
[104]
Ryu C, Munie M, Noorulla S, Edwards P, Qiso X, Gao H. Effect of metformin on the development of diabetic retinopathy. Invest Ophthalmol Vis Sci 2013; 54: 2449.
[105]
Yi QY, Deng G, Chen N, et al. Metformin inhibits development of diabetic retinopathy through inducing alternative splicing of VEGF-A. Am J Transl Res 2016; 8(9): 3947-54.
[PMID: 27725874]
[106]
Li Y, Ryu C, Munie M, et al. Association of Metformin Treatment with Reduced Severity of Diabetic Retinopathy in Type 2 Diabetic Patients. J Diabetes Res 2018; 2018: 2801450.
[http://dx.doi.org/10.1155/2018/2801450] [PMID: 29854819]
[107]
Tan BK, Adya R, Chen J, et al. Metformin decreases angiogenesis via NF-kappaB and Erk1/2/Erk5 pathways by increasing the antiangiogenic thrombospondin-1. Cardiovasc Res 2009; 83(3): 566-74.
[http://dx.doi.org/10.1093/cvr/cvp131] [PMID: 19414528]
[108]
Albini A, Tosetti F, Li VW, Noonan DM, Li WW. Cancer prevention by targeting angiogenesis. Nat Rev Clin Oncol 2012; 9(9): 498-509.
[http://dx.doi.org/10.1038/nrclinonc.2012.120] [PMID: 22850752]
[109]
Kawanami D, Takashi Y, Tanabe M. Significance of Metformin Use in Diabetic Kidney Disease. Int J Mol Sci 2020; 21(12): 4239.
[http://dx.doi.org/10.3390/ijms21124239] [PMID: 32545901]
[110]
Kume S. Pathophysiological roles of nutrient-sensing mechanisms in diabetes and its complications. Diabetol Int 2019; 10(4): 245-9.
[http://dx.doi.org/10.1007/s13340-019-00406-9] [PMID: 31592045]
[111]
Lee EK, Jeong JU, Chang JW, et al. Activation of AMP-activated protein kinase inhibits albumin-induced endoplasmic reticulum stress and apoptosis through inhibition of reactive oxygen species. Nephron, Exp Nephrol 2012; 121(1-2): e38-48.
[http://dx.doi.org/10.1159/000342802] [PMID: 23108012]
[112]
Ishibashi Y, Matsui T, Takeuchi M, Yamagishi S. Metformin inhibits advanced glycation end products (AGEs)-induced renal tubular cell injury by suppressing reactive oxygen species generation via reducing receptor for AGEs (RAGE) expression. Horm Metab Res 2012; 44(12): 891-5.
[http://dx.doi.org/10.1055/s-0032-1321878] [PMID: 22864903]
[113]
Takiyama Y, Harumi T, Watanabe J, et al. Tubular injury in a rat model of type 2 diabetes is prevented by metformin: a possible role of HIF-1α expression and oxygen metabolism. Diabetes 2011; 60(3): 981-92.
[http://dx.doi.org/10.2337/db10-0655] [PMID: 21282369]
[114]
You G, Long X, Song F, et al. Metformin Activates the AMPK-mTOR Pathway by Modulating lncRNA TUG1 to Induce Autophagy and Inhibit Atherosclerosis. Drug Des Devel Ther 2020; 14: 457-68.
[http://dx.doi.org/10.2147/DDDT.S233932] [PMID: 32099330]
[115]
Sirtori CR, Catapano A, Ghiselli GC, Innocenti AL, Rodriguez J. Metaformin: an antiatherosclerotic agent modifying very low density lipoproteins in rabbits. Atherosclerosis 1977; 26(1): 79-89.
[http://dx.doi.org/10.1016/0021-9150(77)90142-3] [PMID: 189780]
[116]
Li SN, Wang X, Zeng QT, et al. Metformin inhibits nuclear factor kappaB activation and decreases serum high-sensitivity C-reactive protein level in experimental atherogenesis of rabbits. Heart Vessels 2009; 24(6): 446-53.
[http://dx.doi.org/10.1007/s00380-008-1137-7] [PMID: 20108078]
[117]
de Aguiar LG, Bahia LR, Villela N, et al. Metformin improves endothelial vascular reactivity in first-degree relatives of type 2 diabetic patients with metabolic syndrome and normal glucose tolerance. Diabetes Care 2006; 29(5): 1083-9.
[http://dx.doi.org/10.2337/dc05-2146] [PMID: 16644641]
[118]
Davis BJ, Xie Z, Viollet B, Zou MH. Activation of the AMP-activated kinase by antidiabetes drug metformin stimulates nitric oxide synthesis in vivo by promoting the association of heat shock protein 90 and endothelial nitric oxide synthase. Diabetes 2006; 55(2): 496-505.
[http://dx.doi.org/10.2337/diabetes.55.02.06.db05-1064] [PMID: 16443786]
[119]
Dong Y, Zhang M, Liang B, et al. Reduction of AMP-activated protein kinase alpha2 increases endoplasmic reticulum stress and atherosclerosis in vivo. Circulation 2010; 121(6): 792-803.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.109.900928] [PMID: 20124121]
[120]
Eriksson L, Nyström T. Activation of AMP-activated protein kinase by metformin protects human coronary artery endothelial cells against diabetic lipoapoptosis. Cardiovasc Diabetol 2014; 13: 152.
[http://dx.doi.org/10.1186/s12933-014-0152-5] [PMID: 25391818]
[121]
Slater RE, Strom JG, Methawasin M, et al. Metformin improves diastolic function in an HFpEF-like mouse model by increasing titin compliance. J Gen Physiol 2019; 151(1): 42-52.
[http://dx.doi.org/10.1085/jgp.201812259] [PMID: 30567709]
[122]
Halabi A, Sen J, Huynh Q, Marwick TH. Metformin treatment in heart failure with preserved ejection fraction: a systematic review and meta-regression analysis. Cardiovasc Diabetol 2020; 19(1): 124.
[http://dx.doi.org/10.1186/s12933-020-01100-w] [PMID: 32758236]
[123]
Jyothirmayi GN, Soni BJ, Masurekar M, Lyons M, Regan TJ. Effects of Metformin on Collagen Glycation and Diastolic Dysfunction in Diabetic Myocardium. J Cardiovasc Pharmacol Ther 1998; 3(4): 319-26.
[http://dx.doi.org/10.1177/107424849800300407] [PMID: 10684514]
[124]
Kuan W, Beavers CJ, Guglin ME. Still sour about lactic acidosis years later: role of metformin in heart failure. Heart Fail Rev 2018; 23(3): 347-53.
[http://dx.doi.org/10.1007/s10741-017-9649-9] [PMID: 28868582]
[125]
Andersson C, Olesen JB, Hansen PR, et al. Metformin treatment is associated with a low risk of mortality in diabetic patients with heart failure: a retrospective nationwide cohort study. Diabetologia 2010; 53(12): 2546-53.
[http://dx.doi.org/10.1007/s00125-010-1906-6] [PMID: 20838985]
[126]
Gu J, Yin ZF, Zhang JF, Wang CQ. Association between long-term prescription of metformin and the progression of heart failure with preserved ejection fraction in patients with type 2 diabetes mellitus and hypertension. Int J Cardiol 2020; 306: 140-5.
[http://dx.doi.org/10.1016/j.ijcard.2019.11.087] [PMID: 31711850]
[127]
Giunti S, Gruden G, Fornengo P, et al. Increased QT interval dispersion predicts 15-year cardiovascular mortality in type 2 diabetic subjects: the population-based Casale Monferrato Study. Diabetes Care 2012; 35(3): 581-3.
[http://dx.doi.org/10.2337/dc11-1397] [PMID: 22301117]
[128]
Wang H, Wang C, Lu Y, et al. Metformin Shortens Prolonged QT Interval in Diabetic Mice by Inhibiting L-Type Calcium Current: A Possible Therapeutic Approach. Front Pharmacol 2020; 11: 614.
[http://dx.doi.org/10.3389/fphar.2020.00614] [PMID: 32595491]
[129]
Müller G. The molecular mechanism of the insulin-mimetic/sensitizing activity of the antidiabetic sulfonylurea drug Amaryl. Mol Med 2000; 6(11): 907-33.
[http://dx.doi.org/10.1007/BF03401827] [PMID: 11147570]
[130]
Maloney A, Rosenstock J, Fonseca V. A Model-Based Meta-Analysis of 24 Antihyperglycemic Drugs for Type 2 Diabetes: Comparison of Treatment Effects at Therapeutic Doses. Clin Pharmacol Ther 2019; 105(5): 1213-23.
[http://dx.doi.org/10.1002/cpt.1307] [PMID: 30457671]
[131]
Royal Australian College of General Practitioners. General practice management of type 2 diabetes 2016–2018 East Melbourne. Vic: RACGP 2016.
[132]
New drugs for type 2 diabetes: second-line therapy science report. Ottawa: CADTH therapeutic review 2017; 4(1)
[133]
Amod A. The Place of Sulfonylureas in Guidelines: Why Are There Differences? Diabetes Ther 2020; 11(Suppl. 1): 5-14.
[http://dx.doi.org/10.1007/s13300-020-00811-3] [PMID: 32323155]
[134]
Black C, Donnelly P, McIntyre L, Royle PL, Shepherd JP, Thomas S. Meglitinide analogues for type 2 diabetes mellitus. Cochrane Database Syst Rev 2007; 2007(2): CD004654.
[http://dx.doi.org/10.1002/14651858.CD004654.pub2] [PMID: 17443551]
[135]
Mohanty BK. Choosing the Best Oral Diabetic Agents in T2 Diabetes Mellitus-Physicians Challenge. J Diabetes Metab 2018; 9: 1-7.
[http://dx.doi.org/10.4172/2155-6156.1000797]
[136]
Scheen AJ. Is there a role for alpha-glucosidase inhibitors in the prevention of type 2 diabetes mellitus? Drugs 2003; 63(10): 933-51.
[http://dx.doi.org/10.2165/00003495-200363100-00002] [PMID: 12699398]
[137]
O’Keefe JH, Bell DS. Postprandial hyperglycemia/hyperlipidemia (postprandial dysmetabolism) is a cardiovascular risk factor. Am J Cardiol 2007; 100(5): 899-904.
[http://dx.doi.org/10.1016/j.amjcard.2007.03.107] [PMID: 17719342]
[138]
O’Keefe JH, Gheewala NM, O’Keefe JO. Dietary strategies for improving post-prandial glucose, lipids, inflammation, and cardiovascular health. J Am Coll Cardiol 2008; 51(3): 249-55.
[http://dx.doi.org/10.1016/j.jacc.2007.10.016] [PMID: 18206731]
[139]
DiNicolantonio JJ, Bhutani J, O’Keefe JH. Acarbose: safe and effective for lowering postprandial hyperglycaemia and improving cardiovascular outcomes. Open Heart 2015; 2(1): e000327.
[http://dx.doi.org/10.1136/openhrt-2015-000327] [PMID: 26512331]
[140]
Ceriello A, Giugliano D, Quatraro A, Dello Russo P, Lefèbvre PJ. Metabolic control may influence the increased superoxide generation in diabetic serum. Diabet Med 1991; 8(6): 540-2.
[http://dx.doi.org/10.1111/j.1464-5491.1991.tb01647.x] [PMID: 1653676]
[141]
Shimabukuro M, Higa N, Chinen I, Yamakawa K, Takasu N. Effects of a single administration of acarbose on postprandial glucose excursion and endothelial dysfunction in type 2 diabetic patients: a randomized crossover study. J Clin Endocrinol Metab 2006; 91(3): 837-42.
[http://dx.doi.org/10.1210/jc.2005-1566] [PMID: 16368744]
[142]
Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M. STOP-NIDDM Trail Research Group. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet 2002; 359(9323): 2072-7.
[http://dx.doi.org/10.1016/S0140-6736(02)08905-5] [PMID: 12086760]
[143]
Kelly IE, Han TS, Walsh K, Lean ME. Effects of a thiazolidinedione compound on body fat and fat distribution of patients with type 2 diabetes. Diabetes Care 1999; 22(2): 288-93. [published correction appears in Diabetes Care 1999 Mar;22(3):536].
[http://dx.doi.org/10.2337/diacare.22.2.288] [PMID: 10333947]
[144]
Einhorn D, Fonseca V. Revisiting the use of pioglitazone in the treatment of type 2 diabetes. Endocr Pract 2016; 22(11): 1343-6.
[http://dx.doi.org/10.4158/EP161409.CO] [PMID: 27540881]
[145]
Gupta S, Gupta K, Ravi R, et al. Pioglitazone and the risk of bladder cancer: An Indian retrospective cohort study. Indian J Endocrinol Metab 2015; 19(5): 639-43.
[http://dx.doi.org/10.4103/2230-8210.163187] [PMID: 26425474]
[146]
Dormandy JA, Charbonnel B, Eckland DJ, et al. PROactive Investigators. 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. Lancet 2005; 366(9493): 1279-89.
[http://dx.doi.org/10.1016/S0140-6736(05)67528-9] [PMID: 16214598]
[147]
Pourshabanan P, Momeni A, Mahmoudnia L, Kheiri S. Effect of pioglitazone on decreasing of proteinuria in type 2 diabetic patients with nephropathy. Diabetes Metab Syndr 2019; 13(1): 132-6.
[http://dx.doi.org/10.1016/j.dsx.2018.04.013] [PMID: 30641685]
[148]
Tang SC, Leung JC, Chan LY, Tsang AW, Lai KN. Activation of tubular epithelial cells in diabetic nephropathy and the role of the peroxisome proliferator-activated receptor-gamma agonist. J Am Soc Nephrol 2006; 17(6): 1633-43.
[http://dx.doi.org/10.1681/ASN.2005101113] [PMID: 16687627]
[149]
Li Y, Wen X, Spataro BC, Hu K, Dai C, Liu Y. hepatocyte growth factor is a downstream effector that mediates the antifibrotic action of peroxisome proliferator-activated receptor-gamma agonists. J Am Soc Nephrol 2006; 17(1): 54-65.
[http://dx.doi.org/10.1681/ASN.2005030257] [PMID: 16291834]
[150]
Idris I, Warren G, Donnelly R. Association between thiazolidinedione treatment and risk of macular edema among patients with type 2 diabetes. Arch Intern Med 2012; 172(13): 1005-11.
[http://dx.doi.org/10.1001/archinternmed.2012.1938] [PMID: 22688528]
[151]
Wright MB, Bortolini M, Tadayyon M, Bopst M. Minireview: Challenges and opportunities in development of PPAR agonists. Mol Endocrinol 2014; 28(11): 1756-68.
[http://dx.doi.org/10.1210/me.2013-1427] [PMID: 25148456]
[152]
Balakumar P, Rose M, Ganti SS, Krishan P, Singh M. PPAR dual agonists: are they opening Pandora’s Box? Pharmacol Res 2007; 56(2): 91-8.
[http://dx.doi.org/10.1016/j.phrs.2007.03.002] [PMID: 17428674]
[153]
Kaul U, Parmar D, Manjunath K, et al. New dual peroxisome proliferator activated receptor agonist-Saroglitazar in diabetic dyslipidemia and non-alcoholic fatty liver disease: integrated analysis of the real world evidence. Cardiovasc Diabetol 2019; 18(1): 80.
[http://dx.doi.org/10.1186/s12933-019-0884-3] [PMID: 31208414]
[154]
Sosale A, Saboo B, Sosale B. Saroglitazar for the treatment of hypertrig-lyceridemia in patients with type 2 diabetes: current evidence. Diabetes Metab Syndr Obes 2015; 8: 189-96.
[http://dx.doi.org/10.2147/DMSO.S49592] [PMID: 25926748]
[155]
Yabe D, Kuwata H, Seino Y. The journey to understanding incretin systems: Theory, practice and more theory. J Diabetes Investig 2019; 10(5): 1171-3.
[http://dx.doi.org/10.1111/jdi.13123] [PMID: 31361402]
[156]
Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev 2007; 87(4): 1409-39.
[http://dx.doi.org/10.1152/physrev.00034.2006] [PMID: 17928588]
[157]
Antza C, Nirantharakumar K, Doundoulakis I, Tahrani AA, Toulis KA. The development of an oral GLP-1 receptor agonist for the management of type 2 diabetes: evidence to date. Drug Des Devel Ther 2019; 13: 2985-96.
[http://dx.doi.org/10.2147/DDDT.S166765] [PMID: 31686781]
[158]
Doyle ME, Egan JM. Mechanisms of action of glucagon-like peptide 1 in the pancreas. Pharmacol Ther 2007; 113(3): 546-93.
[http://dx.doi.org/10.1016/j.pharmthera.2006.11.007] [PMID: 17306374]
[159]
Guthrie R. Practice pearl: liraglutide and cardiovascular and renal events in type 2 diabetes. Postgrad Med 2018; 130(2): 154-8.
[http://dx.doi.org/10.1080/00325481.2018.1430446] [PMID: 29350569]
[160]
Pfeffer MA, Claggett B, Diaz R, et al. ELIXA Investigators. Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome. N Engl J Med 2015; 373(23): 2247-57.
[http://dx.doi.org/10.1056/NEJMoa1509225] [PMID: 26630143]
[161]
Tuttle KR, McKinney TD, Davidson JA, Anglin G, Harper KD, Botros FT. Effects of once-weekly dulaglutide on kidney function in patients with type 2 diabetes in phase II and III clinical trials. Diabetes Obes Metab 2017; 19(3): 436-41.
[http://dx.doi.org/10.1111/dom.12816] [PMID: 27766728]
[162]
Tuttle KR, Lakshmanan MC, 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. Lancet Diabetes Endocrinol 2018; 6(8): 605-17.
[http://dx.doi.org/10.1016/S2213-8587(18)30104-9] [PMID: 29910024]
[163]
Kang YM, Jung CH. Effects of Incretin-Based Therapies on Diabetic Microvascular Complications. Endocrinol Metab (Seoul) 2017; 32(3): 316-25.
[http://dx.doi.org/10.3803/EnM.2017.32.3.316] [PMID: 28956360]
[164]
Newman JD, Vani AK, Aleman JO, Weintraub HS, Berger JS, Schwartzbard AZ. The changing landscape of diabetes therapy for cardiovascular risk reduction: JACC state-of-the-art review. J Am Coll Cardiol 2018; 72(15): 1856-69.
[http://dx.doi.org/10.1016/j.jacc.2018.07.071] [PMID: 30286929]
[165]
Timmers L, Henriques JP, de Kleijn DP, et al. Exenatide reduces infarct size and improves cardiac function in a porcine model of ischemia and reperfusion injury. J Am Coll Cardiol 2009; 53(6): 501-10.
[http://dx.doi.org/10.1016/j.jacc.2008.10.033] [PMID: 19195607]
[166]
Nyström T, Gutniak MK, Zhang Q, et al. Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease. Am J Physiol Endocrinol Metab 2004; 287(6): E1209-15.
[http://dx.doi.org/10.1152/ajpendo.00237.2004] [PMID: 15353407]
[167]
Sokos GG, Nikolaidis LA, Mankad S, Elahi D, Shannon RP. Glucagon-like peptide-1 infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure. J Card Fail 2006; 12(9): 694-9.
[http://dx.doi.org/10.1016/j.cardfail.2006.08.211] [PMID: 17174230]
[168]
Secrest MH, Udell JA, Filion KB. The cardiovascular safety trials of DPP-4 inhibitors, GLP-1 agonists, and SGLT2 inhibitors. Trends Cardiovasc Med 2017; 27(3): 194-202.
[http://dx.doi.org/10.1016/j.tcm.2017.01.009] [PMID: 28291655]
[169]
Song X, Jia H, Jiang Y, et al. Anti-atherosclerotic effects of the glucagon-like peptide-1 (GLP-1) based therapies in patients with type 2 Diabetes Mellitus: A meta-analysis. Sci Rep 2015; 5: 10202.
[http://dx.doi.org/10.1038/srep10202] [PMID: 26111974]
[170]
Sinha B, Ghosal S. Meta-analyses of the effects of DPP-4 inhibitors, SGLT2 inhibitors and GLP1 receptor analogues on cardiovascular death, myocardial infarction, stroke and hospitalization for heart failure. Diabetes Res Clin Pract 2019; 150: 8-16.
[http://dx.doi.org/10.1016/j.diabres.2019.02.014] [PMID: 30794833]
[171]
Bizino MB, Jazet IM, Westenberg JJM, et al. Effect of liraglutide on cardiac function in patients with type 2 diabetes mellitus: randomized placebo-controlled trial. Cardiovasc Diabetol 2019; 18(1): 55. [published correction appears in Cardiovasc Diabetol. 2019 Aug 9;18(1):101].
[http://dx.doi.org/10.1186/s12933-019-0857-6] [PMID: 31039778]
[172]
Dozio E, Vianello E, Malavazos AE, et al. Epicardial adipose tissue GLP-1 receptor is associated with genes involved in fatty acid oxidation and white-to-brown fat differentiation: A target to modulate cardiovascular risk? Int J Cardiol 2019; 292: 218-24.
[http://dx.doi.org/10.1016/j.ijcard.2019.04.039] [PMID: 31023563]
[173]
Marsico F, Paolillo S, Gargiulo P, et al. Effects of glucagon-like peptide-1 receptor agonists on major cardiovascular events in patients with Type 2 diabetes mellitus with or without established cardiovascular disease: a meta-analysis of randomized controlled trials. Eur Heart J 2020.
[174]
Marso SP, Daniels GH, Brown-Frandsen K, et al. LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2016; 375(4): 311-22.
[http://dx.doi.org/10.1056/NEJMoa1603827] [PMID: 27295427]
[175]
Kristensen SL, Rørth R, Jhund PS, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol 2019; 7(10): 776-85. [published correction appears in Lancet Diabetes Endocrinol. 2020 Mar;8(3):e2].
[http://dx.doi.org/10.1016/S2213-8587(19)30249-9] [PMID: 31422062]
[176]
Yu M, Moreno C, Hoagland KM, et al. Antihypertensive effect of glucagon-like peptide 1 in Dahl salt-sensitive rats. J Hypertens 2003; 21(6): 1125-35.
[http://dx.doi.org/10.1097/00004872-200306000-00012] [PMID: 12777949]
[177]
Barragán JM, Rodríguez RE, Blázquez E. Changes in arterial blood pressure and heart rate induced by glucagon-like peptide-1-(7-36) amide in rats. Am J Physiol 1994; 266(3 Pt 1): E459-66.
[http://dx.doi.org/10.1152/ajpendo.1994.266.3.E459] [PMID: 8166268]
[178]
Ban K, Noyan-Ashraf MH, Hoefer J, Bolz SS, Drucker DJ, Husain M. Cardioprotective and vasodilatory actions of glucagon- like peptide 1 receptor are mediated through both glucagon-like peptide 1 receptor-dependent and -independent pathways. Circulation 2008; 117(18): 2340-50. [published correction appears in Circulation. 2008 Jul 22;118(4):e81].
[http://dx.doi.org/10.1161/CIRCULATIONAHA.107.739938] [PMID: 18427132]
[179]
Poornima I, Brown SB, Bhashyam S, Parikh P, Bolukoglu H, Shannon RP. Chronic glucagon-like peptide-1 infusion sustains left ventricular systolic function and prolongs survival in the spontaneously hypertensive, heart failure-prone rat. Circ Heart Fail 2008; 1(3): 153-60.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.108.766402] [PMID: 19727407]
[180]
Godinho R, Mega C, Teixeira-de-Lemos E, et al. The Place of Dipeptidyl Peptidase-4 Inhibitors in Type 2 Diabetes Therapeutics: A “Me Too” or “the Special One” Antidiabetic Class? J Diabetes Res 2015; 2015: 806979.
[http://dx.doi.org/10.1155/2015/806979] [PMID: 26075286]
[181]
McDougall C, McKay GA, Fisher M. Drugs for diabetes: Part 5 DPP-4 inhibitors. Br J Cardiol 2011; 18(3): 130-2.
[182]
Chahal H, Chowdhury TA. Gliptins: a new class of oral hypoglycaemic agent. QJM 2007; 100(11): 671-7.
[http://dx.doi.org/10.1093/qjmed/hcm081] [PMID: 17881415]
[183]
Deacon CF. Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes: a comparative review. Diabetes Obes Metab 2011; 13(1): 7-18.
[http://dx.doi.org/10.1111/j.1463-1326.2010.01306.x] [PMID: 21114598]
[184]
Longato E, Di Camillo B, Sparacino G, Tramontan L, Avogaro A, Fadini GP. Better cardiovascular outcomes of type 2 diabetic patients treated with GLP-1 receptor agonists versus DPP-4 inhibitors in clinical practice. Cardiovasc Diabetol 2020; 19(1): 74.
[http://dx.doi.org/10.1186/s12933-020-01049-w] [PMID: 32522260]
[185]
Mosenzon O, Leibowitz G, Bhatt DL, et al. Effect of Saxagliptin on Renal Outcomes in the SAVOR-TIMI 53 Trial. Diabetes Care 2017; 40(1): 69-76.
[http://dx.doi.org/10.2337/dc16-0621] [PMID: 27797925]
[186]
El Mouhayyar C, Riachy R, Khalil AB, Eid A, Azar S. SGLT2 Inhibitors, GLP-1 Agonists, and DPP-4 Inhibitors in Diabetes and Microvascular Complications: A Review. Int J Endocrinol 2020; 2020: 1762164.
[http://dx.doi.org/10.1155/2020/1762164] [PMID: 32190049]
[187]
Gonçalves A, Marques C, Leal E, et al. Dipeptidyl peptidase-IV inhibition prevents blood-retinal barrier breakdown, inflammation and neuronal cell death in the retina of type 1 diabetic rats. Biochim Biophys Acta 2014; 1842(9): 1454-63.
[http://dx.doi.org/10.1016/j.bbadis.2014.04.013] [PMID: 24769045]
[188]
Maeda S, Yamagishi S, Matsui T, et al. Beneficial effects of vildagliptin on retinal injury in obese type 2 diabetic rats. Ophthalmic Res 2013; 50(4): 221-6.
[http://dx.doi.org/10.1159/000354116] [PMID: 24081217]
[189]
Chung YR, Park SW, Kim JW, Kim JH, Lee K. Protective effects of dipeptidyl peptidase-4 inhibitors on progression of diabetic retinopathy in patients with type 2 diabetes. Retina 2016; 36(12): 2357-63.
[http://dx.doi.org/10.1097/IAE.0000000000001098] [PMID: 27285457]
[190]
Kolaczynski WM, Hankins M, Ong SH, Richter H, Clemens A, Toussi M. Microvascular Outcomes in Patients with Type 2 Diabetes Treated with Vildagliptin vs. Sulfonylurea: A Retrospective Study Using German Electronic Medical Records. Diabetes Ther 2016; 7(3): 483-96.
[http://dx.doi.org/10.1007/s13300-016-0177-8] [PMID: 27262995]
[191]
Tsuboi K, Mizukami H, Inaba W, Baba M, Yagihashi S. The dipeptidyl peptidase IV inhibitor vildagliptin suppresses development of neuropathy in diabetic rodents: effects on peripheral sensory nerve function, structure and molecular changes. J Neurochem 2016; 136(4): 859-70.
[http://dx.doi.org/10.1111/jnc.13439] [PMID: 26603140]
[192]
Scirica BM, Braunwald E, Raz I, et al. SAVOR-TIMI 53 steering committee and investigators. heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. Circulation 2015; 132(15): e198.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.115.015511] [PMID: 26459088]
[193]
Zannad F, Cannon CP, Cushman WC, et al. EXAMINE Investigators. Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial. Lancet 2015; 385(9982): 2067-76.
[http://dx.doi.org/10.1016/S0140-6736(14)62225-X] [PMID: 25765696]
[194]
Rosenstock J, Perkovic V, Alexander JH, et al. CARMELINA® investigators. Rationale, design, and baseline characteristics of the cardiovascular safety and Renal Microvascular outcomE study with LINAgliptin (CARMELINA®): a randomized, double-blind, placebo-controlled clinical trial in patients with type 2 diabetes and high cardio-renal risk. Cardiovasc Diabetol 2018; 17(1): 39.
[http://dx.doi.org/10.1186/s12933-018-0682-3] [PMID: 29540217]
[195]
Green JB, Bethel MA, Paul SK, et al. Rationale, design, and organization of a randomized, controlled Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) in patients with type 2 diabetes and established cardiovascular disease. Am Heart J 2013; 166(6): 983-989.e7.
[http://dx.doi.org/10.1016/j.ahj.2013.09.003] [PMID: 24268212]
[196]
Khalse M, Bhargava A. A Review on cardiovascular outcome studies of dipeptidyl peptidase-4 inhibitors. Indian J Endocrinol Metab 2018; 22(5): 689-95.
[http://dx.doi.org/10.4103/ijem.IJEM_104_18] [PMID: 30294582]
[197]
Satoh-Asahara N, Sasaki Y, Wada H, et al. A dipeptidyl peptidase-4 inhibitor, sitagliptin, exerts anti-inflammatory effects in type 2 diabetic patients. Metabolism 2013; 62(3): 347-51.
[http://dx.doi.org/10.1016/j.metabol.2012.09.004] [PMID: 23062489]
[198]
Baltzis D, Dushay JR, Loader J, et al. Effect of linagliptin on vascular function: A randomized, placebo-controlled study. J Clin Endocrinol Metab 2016; 101(11): 4205-13.
[http://dx.doi.org/10.1210/jc.2016-2655] [PMID: 27583476]
[199]
Nakamura Y, Tsuji M, Hasegawa H, et al. Anti-inflammatory effects of linagliptin in hemodialysis patients with diabetes. Hemodial Int 2014; 18(2): 433-42.
[http://dx.doi.org/10.1111/hdi.12127] [PMID: 24405885]
[200]
Fadini GP, Boscaro E, Albiero M, et al. The oral dipeptidyl peptidase-4 inhibitor sitagliptin increases circulating endothelial progenitor cells in patients with type 2 diabetes: possible role of stromal-derived factor-1alpha. Diabetes Care 2010; 33(7): 1607-9.
[http://dx.doi.org/10.2337/dc10-0187] [PMID: 20357375]
[201]
Widlansky ME, Puppala VK, Suboc TM, et al. Impact of DPP-4 inhibition on acute and chronic endothelial function in humans with type 2 diabetes on background metformin therapy. Vasc Med 2017; 22(3): 189-96.
[http://dx.doi.org/10.1177/1358863X16681486] [PMID: 28145158]
[202]
Coady MJ, Wallendorff B, Lapointe JY. Characterization of the transport activity of SGLT2/MAP17, the renal low-affinity Na+-glucose cotransporter. Am J Physiol Renal Physiol 2017; 313(2): E467-F474.
[http://dx.doi.org/10.1152/ajprenal.00628.2016] [PMID: 28592437]
[203]
Ghosh RK, Ghosh SM, Chawla S, Jasdanwala SA. SGLT2 inhibitors: a new emerging therapeutic class in the treatment of type 2 diabetes mellitus. J Clin Pharmacol 2012; 52(4): 457-63.
[http://dx.doi.org/10.1177/0091270011400604] [PMID: 21543663]
[204]
https://www.medscape.org/viewarticle/578176
[205]
Hardman TC, Dubrey SW. Development and potential role of type-2 sodium-glucose transporter inhibitors for management of type 2 diabetes. Diabetes Ther 2011; 2(3): 133-45.
[http://dx.doi.org/10.1007/s13300-011-0004-1] [PMID: 22127823]
[206]
Song P, Onishi A, Koepsell H, Vallon V. Sodium glucose cotransporter SGLT1 as a therapeutic target in diabetes mellitus. Expert Opin Ther Targets 2016; 20(9): 1109-25.
[http://dx.doi.org/10.1517/14728222.2016.1168808] [PMID: 26998950]
[207]
Santos LL, Lima FJC, Sousa-Rodrigues CF, Barbosa FT. Use of SGLT-2 inhibitors in the treatment of type 2 diabetes mellitus. Rev Assoc Med Bras 2017; 63(7): 636-41.
[208]
Reed JW. Impact of sodium-glucose cotransporter 2 inhibitors on blood pressure. Vasc Health Risk Manag 2016; 12: 393-405.
[http://dx.doi.org/10.2147/VHRM.S111991] [PMID: 27822054]
[209]
List JF, Whaley JM. Glucose dynamics and mechanistic implications of SGLT2 inhibitors in animals and humans. Kidney Int Suppl 2011; (120): S20-7.
[http://dx.doi.org/10.1038/ki.2010.512] [PMID: 21358698]
[210]
Kalra S, Shetty KK, Nagarajan VB, Ved JK. Basic and Clinical Pharmaco-Therapeutics of SGLT2 Inhibitors: A Contemporary Update. Diabetes Ther 2020; 11(4): 813-33.
[http://dx.doi.org/10.1007/s13300-020-00789-y] [PMID: 32130664]
[211]
Takakura S, Toyoshi T, Hayashizaki Y, Takasu T. Effect of ipragliflozin, an SGLT2 inhibitor, on progression of diabetic microvascular complications in spontaneously diabetic Torii fatty rats. Life Sci 2016; 147: 125-31.
[http://dx.doi.org/10.1016/j.lfs.2016.01.042] [PMID: 26829386]
[212]
Zinman B, Wanner C, Lachin JM, et al. EMPA-REG OUTCOME Investigators. 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]
[213]
Nagahisa T, Saisho Y. Cardiorenal Protection: Potential of SGLT2 Inhibitors and GLP-1 Receptor Agonists in the Treatment of Type 2 Diabetes. Diabetes Ther 2019; 10(5): 1733-52.
[http://dx.doi.org/10.1007/s13300-019-00680-5] [PMID: 31440988]
[214]
Wiviott SD, Raz I, Bonaca MP, et al. DECLARE–TIMI 58 Investigators. 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]
[215]
Kruger D, Valentine V. Canagliflozin for the treatment of diabetic kidney disease and implications for clinical practice: a narrative review. Diabetes Ther 2020; 11(6): 1237-50.
[http://dx.doi.org/10.1007/s13300-020-00826-w] [PMID: 32405876]
[216]
Association AD. 1. Improving Care and Promoting Health in Populations: Standards of Medical Care in Diabetes-2020. Diabetes Care 2020; 43(Suppl. 1): S7-S13.
[http://dx.doi.org/10.2337/dc20-S001] [PMID: 31862744]
[217]
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. Lancet Diabetes Endocrinol 2019; 7(6): 429-41.
[http://dx.doi.org/10.1016/S2213-8587(19)30086-5] [PMID: 30992195]
[218]
Chamberlain JJ, Doyle-Delgado K, Peterson L, Skolnik N. Diabetes technology: review of the 2019 american diabetes association standards of medical care in diabetes. Ann Intern Med 2019; 171(6): 415-20.
[http://dx.doi.org/10.7326/M19-1638] [PMID: 31404925]
[219]
Cannon CP, McGuire DK, Pratley R, et al. VERTIS-CV Investigators. Design and baseline characteristics of the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes trial (VERTIS-CV). Am Heart J 2018; 206: 11-23.
[http://dx.doi.org/10.1016/j.ahj.2018.08.016] [PMID: 30290289]
[220]
https://clinicaltrials.gov/ct2/show/NCT03036150
[221]
https://clinicaltrials.gov/ct2/show/NCT03594110
[222]
Tanaka A, Shimabukuro M, Okada Y, et al. PROCEED trial investigators. Rationale and design of an investigator-initiated, multicenter, prospective open-label, randomized trial to evaluate the effect of ipragliflozin on endothelial dysfunction in type 2 diabetes and chronic kidney disease: the PROCEED trial. Cardiovasc Diabetol 2020; 19(1): 85.
[http://dx.doi.org/10.1186/s12933-020-01065-w] [PMID: 32534578]
[223]
Tang L, Wu Y, Tian M, et al. Dapagliflozin slows the progression of the renal and liver fibrosis associated with type 2 diabetes. Am J Physiol Endocrinol Metab 2017; 313(5): E563-76.
[http://dx.doi.org/10.1152/ajpendo.00086.2017] [PMID: 28811292]
[224]
Ojima A, Matsui T, Nishino Y, Nakamura N, Yamagishi S. Empagliflozin, an inhibitor of sodium-glucose cotransporter 2 exerts anti-inflammatory and antifibrotic effects on experimental diabetic nephropathy partly by suppressing AGEs-receptor axis. Horm Metab Res 2015; 47(9): 686-92.
[http://dx.doi.org/10.1055/s-0034-1395609] [PMID: 25611208]
[225]
Bonnet F, Scheen AJ. Effects of SGLT2 inhibitors on systemic and tissue low-grade inflammation: The potential contribution to diabetes complications and cardiovascular disease. Diabetes Metab 2018; 44(6): 457-64.
[http://dx.doi.org/10.1016/j.diabet.2018.09.005] [PMID: 30266577]
[226]
Vallon V, Rose M, Gerasimova M, et al. Knockout of Na-glucose transporter SGLT2 attenuates hyperglycemia and glomerular hyperfiltration but not kidney growth or injury in diabetes mellitus. Am J Physiol Renal Physiol 2013; 304(2): F156-67.
[http://dx.doi.org/10.1152/ajprenal.00409.2012] [PMID: 23152292]
[227]
Johnson RJ, Nakagawa T, Jalal D, Sánchez-Lozada LG, Kang DH, Ritz E. Uric acid and chronic kidney disease: which is chasing which? Nephrol Dial Transplant 2013; 28(9): 2221-8.
[http://dx.doi.org/10.1093/ndt/gft029] [PMID: 23543594]
[228]
Kawada T. Sodium-glucose co-transporter 2 inhibitors and serum uric acid. Curr Med Res Opin 2019; 35(2): 179-80.
[http://dx.doi.org/10.1080/03007995.2018.1546680] [PMID: 30411637]
[229]
Mende C. Management of Chronic Kidney Disease: The Relationship Between Serum Uric Acid and Development of Nephropathy. Adv Ther 2015; 32(12): 1177-91.
[http://dx.doi.org/10.1007/s12325-015-0272-7] [PMID: 26650815]
[230]
Arow M, Waldman M, Yadin D, et al. Sodium-glucose cotransporter 2 inhibitor Dapagliflozin attenuates diabetic cardiomyopathy. Cardiovasc Diabetol 2020; 19(1): 7.
[http://dx.doi.org/10.1186/s12933-019-0980-4] [PMID: 31924211]
[231]
Thomson SC, Rieg T, Miracle C, et al. Acute and chronic effects of SGLT2 blockade on glomerular and tubular function in the early diabetic rat. Am J Physiol Regul Integr Comp Physiol 2012; 302(1): R75-83.
[http://dx.doi.org/10.1152/ajpregu.00357.2011] [PMID: 21940401]
[232]
Sugiyama S, Jinnouchi H, Kurinami N, et al. Impact of dapagliflozin therapy on renal protection and kidney morphology in patients with ucontrolled type 2 diabetes mellitus. J Clin Med Res 2018; 10(6): 466-77.
[http://dx.doi.org/10.14740/jocmr3419w] [PMID: 29707088]
[233]
Cersosimo E, DeFronzo RA. Insulin resistance and endothelial dysfunction: the road map to cardiovascular diseases. Diabetes Metab Res Rev 2006; 22(6): 423-36.
[http://dx.doi.org/10.1002/dmrr.634] [PMID: 16506274]
[234]
Oelze M, Kröller-Schön S, Welschof P, et al. The sodium-glucose co-transporter 2 inhibitor empagliflozin improves diabetes-induced vascular dysfunction in the streptozotocin diabetes rat model by interfering with oxidative stress and glucotoxicity. PLoS One 2014; 9(11): e112394.
[http://dx.doi.org/10.1371/journal.pone.0112394] [PMID: 25402275]
[235]
Hwang IC, Cho GY, Yoon YE, et al. Different effects of SGLT2 inhibitors according to the presence and types of heart failure in type 2 diabetic patients. Cardiovasc Diabetol 2020; 19(1): 69.
[http://dx.doi.org/10.1186/s12933-020-01042-3] [PMID: 32466760]
[236]
Chen HY, Huang JY, Siao WZ, Jong GP. The association between SGLT2 inhibitors and new-onset arrhythmias: a nationwide population-based longitudinal cohort study. Cardiovasc Diabetol 2020; 19(1): 73.
[http://dx.doi.org/10.1186/s12933-020-01048-x] [PMID: 32503541]
[237]
Zelniker TA, Wiviott SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet 2019; 393(10166): 31-9. [published correction appears in Lancet. 2019 Jan 5;393(10166):30].
[http://dx.doi.org/10.1016/S0140-6736(18)32590-X] [PMID: 30424892]
[238]
Connelly KA, Zhang Y, Desjardins JF, et al. Load-independent effects of empagliflozin contribute to improved cardiac function in experimental heart failure with reduced ejection fraction. Cardiovasc Diabetol 2020; 19(1): 13.
[http://dx.doi.org/10.1186/s12933-020-0994-y] [PMID: 32035482]
[239]
Neal B, Perkovic V, Mahaffey KW, et al. CANVAS program collaborative group. 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]
[240]
Kosiborod M, Cavender MA, Fu AZ, et al. CVD-REAL investigators and study group*. lower risk of heart failure and death in patients initiated on dodium-glucose cotransporter-2 inhibitors versus other glucose-lowering drugs: The CVD-REAL study (comparative effectiveness of cardiovascular outcomes in new users of sodium-glucose cotransporter-2 inhibitors). Circulation 2017; 136(3): 249-59.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.117.029190] [PMID: 28522450]
[241]
Lahnwong S, Palee S, Apaijai N, et al. Acute dapagliflozin administration exerts cardioprotective effects in rats with cardiac ischemia/reperfusion injury. Cardiovasc Diabetol 2020; 19(1): 91.
[http://dx.doi.org/10.1186/s12933-020-01066-9] [PMID: 32539724]
[242]
McMurray JJV, DeMets DL, Inzucchi SE, et al. DAPA-HF Committees and Investigators. A trial to evaluate the effect of the sodium-glucose co-transporter 2 inhibitor dapagliflozin on morbidity and mortality in patients with heart failure and reduced left ventricular ejection fraction (DAPA-HF). Eur J Heart Fail 2019; 21(5): 665-75.
[http://dx.doi.org/10.1002/ejhf.1432] [PMID: 30895697]
[243]
Soga F, Tanaka H, Tatsumi K, et al. Impact of dapagliflozin on left ventricular diastolic function of patients with type 2 diabetic mellitus with chronic heart failure. Cardiovasc Diabetol 2018; 17(1): 132.
[http://dx.doi.org/10.1186/s12933-018-0775-z] [PMID: 30296931]
[244]
Tanaka H, Soga F, Tatsumi K, et al. Positive effect of dapagliflozin on left ventricular longitudinal function for type 2 diabetic mellitus patients with chronic heart failure. Cardiovasc Diabetol 2020; 19(1): 6.
[http://dx.doi.org/10.1186/s12933-019-0985-z] [PMID: 31910853]
[245]
Singh JSS, Mordi IR, Vickneson K, et al. Dapagliflozin versus placebo on left ventricular remodeling in patients with diabetes and heart failure: the reform trial. Diabetes Care 2020; 43(6): 1356-9.
[http://dx.doi.org/10.2337/dc19-2187] [PMID: 32245746]
[246]
Lahnwong S, Chattipakorn SC, Chattipakorn N. Potential mechanisms responsible for cardioprotective effects of sodium-glucose co-transporter 2 inhibitors. Cardiovasc Diabetol 2018; 17(1): 101.
[http://dx.doi.org/10.1186/s12933-018-0745-5] [PMID: 29991346]
[247]
FDA approves new treatment for a type of heart failure 2020.https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-type-heart-failure
[248]
Ahrén B. Glucagon-like peptide-1 receptor agonists for type 2 diabetes: A rational drug development. J Diabetes Investig 2019; 10(2): 196-201.
[http://dx.doi.org/10.1111/jdi.12911] [PMID: 30099845]
[249]
Sharma D, Verma S, Vaidya S, Kalia K, Tiwari V. Recent updates on GLP-1 agonists: Current advancements & challenges. Biomed Pharmacother 2018; 108: 952-62.
[http://dx.doi.org/10.1016/j.biopha.2018.08.088] [PMID: 30372907]
[250]
Drab SR. Glucagon-Like Peptide-1 Receptor Agonists for Type 2 Diabetes: A Clinical Update of Safety and Efficacy. Curr Diabetes Rev 2016; 12(4): 403-13.
[http://dx.doi.org/10.2174/1573399812666151223093841] [PMID: 26694823]
[251]
Xie W, Song X, Liu Z. Impact of dipeptidyl-peptidase 4 inhibitors on cardiovascular diseases. Vascul Pharmacol 2018; 109: 17-26.
[http://dx.doi.org/10.1016/j.vph.2018.05.010] [PMID: 29879463]
[252]
Ling J, Ge L, Zhang DH, et al. DPP-4 inhibitors for the treatment of type 2 diabetes: a methodology overview of systematic reviews. Acta Diabetol 2019; 56(1): 7-27.
[http://dx.doi.org/10.1007/s00592-018-1164-5] [PMID: 29858660]
[253]
Kushwaha RN, Haq W, Katti SB. Sixteen-years of clinically relevant dipeptidyl peptidase-IV (DPP-IV) inhibitors for treatment of type-2 diabetes: a perspective. Curr Med Chem 2014; 21(35): 4013-45.
[http://dx.doi.org/10.2174/0929867321666140915143309] [PMID: 25245373]
[254]
Hsia DS, Grove O, Cefalu WT. An update on sodium-glucose co- transporter-2 inhibitors for the treatment of diabetes mellitus. Curr Opin Endocrinol Diabetes Obes 2017; 24(1): 73-9.
[http://dx.doi.org/10.1097/MED.0000000000000311] [PMID: 27898586]
[255]
Kshirsagar RP, Kulkarni AA, Chouthe RS. SGLT inhibitors as antidiabetic agents: a comprehensive review. RSC Advances 2020; 10: 1733.
[http://dx.doi.org/10.1039/C9RA08706K]
[256]
Anderson RA, Mascarello A, Natanael D, et al. Synthetic Strategies toward SGLT2 Inhibitors. Org Process Res Dev 2019; 23(7): 1471-5.
[http://dx.doi.org/10.1021/acs.oprd.9b00145]
[257]
Belete TM. A Recent Achievement In the Discovery and Development of Novel Targets for the Treatment of Type-2 Diabetes Mellitus. J Exp Pharmacol 2020; 12: 1-15.
[http://dx.doi.org/10.2147/JEP.S226113] [PMID: 32021494]
[258]
Scheen AJ, Paquot N, Lefèbvre PJ. Investigational glucagon receptor antagonists in Phase I and II clinical trials for diabetes. Expert Opin Investig Drugs 2017; 26(12): 1373-89.
[http://dx.doi.org/10.1080/13543784.2017.1395020] [PMID: 29052441]
[259]
Vella A, Freeman JLR, Dunn I, Keller K, Buse JB, Valcarce C. Targeting hepatic glucokinase to treat diabetes with TTP399, a hepatoselective glucokinase activator. Sci Transl Med 2019; 11(475): eaau3441.
[http://dx.doi.org/10.1126/scitranslmed.aau3441] [PMID: 30651321]
[260]
Gizak A, Duda P, Wisniewski J, Rakus D. Fructose-1,6-bisphosphatase: From a glucose metabolism enzyme to multifaceted regulator of a cell fate. Adv Biol Regul 2019; 72: 41-50.
[http://dx.doi.org/10.1016/j.jbior.2019.03.001] [PMID: 30871972]
[261]
Buse MG. Hexosamines, insulin resistance, and the complications of diabetes: current status. Am J Physiol Endocrinol Metab 2006; 290(1): E1-8.
[http://dx.doi.org/10.1152/ajpendo.00329.2005] [PMID: 16339923]
[262]
Mayers RM, Leighton B, Kilgour E. PDH kinase inhibitors: a novel therapy for Type II diabetes? Biochem Soc Trans 2005; 33(Pt 2): 367-70.
[http://dx.doi.org/10.1042/BST0330367] [PMID: 15787608]
[263]
Grewal AS, Bhardwaj S, Pandita D, Lather V, Sekhon BS. Updates on Aldose Reductase Inhibitors for Management of Diabetic Complications and Non-diabetic Diseases. Mini Rev Med Chem 2016; 16(2): 120-62.
[http://dx.doi.org/10.2174/1389557515666150909143737] [PMID: 26349493]
[264]
Waring MJ, Birch AM, Birtles S, et al. Optimisation of biphenyl acetic acid inhibitors of diacylglycerol acetyl transferase 1–the discovery of AZD2353. MedChemComm 2013; 4(1): 159-64.
[http://dx.doi.org/10.1039/C2MD20190A]
[265]
McCallum RW, Lembo A, Esfandyari T, et al. TZP-102 Phase 2b Study Group. Phase 2b, randomized, double-blind 12-week studies of TZP-102, a ghrelin receptor agonist for diabetic gastroparesis. Neurogastroenterol Motil 2013; 25(11): e705-17.
[http://dx.doi.org/10.1111/nmo.12184] [PMID: 23848826]
[266]
Donath MY. Targeting inflammation in the treatment of type 2 diabetes: time to start. Nat Rev Drug Discov 2014; 13(6): 465-76.
[http://dx.doi.org/10.1038/nrd4275] [PMID: 24854413]
[267]
Kim JH, Bae KH, Choi YK, et al. Fibroblast growth factor 21 analogue LY2405319 lowers blood glucose in streptozotocin-induced insulin-deficient diabetic mice by restoring brown adipose tissue function. Diabetes Obes Metab 2015; 17(2): 161-9.
[http://dx.doi.org/10.1111/dom.12408] [PMID: 25359298]
[268]
Nguyen LT, Chen H, Mak C, Zaky A, Pollock C, Saad S. SRT1720 attenuates obesity and insulin resistance but not liver damage in the offspring due to maternal and postnatal high-fat diet consumption. Am J Physiol Endocrinol Metab 2018; 315(2): E196-203.
[http://dx.doi.org/10.1152/ajpendo.00472.2017] [PMID: 29533740]
[269]
Patil PD, Mahajan UB, Patil KR, et al. Past and current perspective on new therapeutic targets for Type-II diabetes. Drug Des Devel Ther 2017; 11: 1567-83.
[http://dx.doi.org/10.2147/DDDT.S133453] [PMID: 28579755]
[270]
Anagnostis P, Katsiki N, Adamidou F, et al. 11beta-Hydroxysteroid dehydrogenase type 1 inhibitors: novel agents for the treatment of metabolic syndrome and obesity-related disorders? Metabolism 2013; 62(1): 21-33.
[http://dx.doi.org/10.1016/j.metabol.2012.05.002] [PMID: 22652056]
[271]
Harriman G, Greenwood J, Bhat S, et al. Acetyl-CoA carboxylase inhibition by ND-630 reduces hepatic steatosis, improves insulin sensitivity, and modulates dyslipidemia in rats. Proc Natl Acad Sci USA 2016; 113(13): E1796-805.
[http://dx.doi.org/10.1073/pnas.1520686113] [PMID: 26976583]
[272]
Lu J, Gong D, Choong SY, et al. Copper(II)-selective chelation improves function and antioxidant defences in cardiovascular tissues of rats as a model of diabetes: comparisons between triethylenetetramine and three less copper-selective transition-metal- targeted treatments. Diabetologia 2010; 53(6): 1217-26.
[http://dx.doi.org/10.1007/s00125-010-1698-8] [PMID: 20221822]
[273]
Kang Y, Zhang X, Cai Y, Su J, Kong X. Gut microbiota and metabolic disease: from pathogenesis to new therapeutic strategies. Reviews in Medical Microbiology 2016; 27(4): 141-52.
[274]
Zhou H, Sun L, Zhang S, Zhao X, Gang X, Wang G. Evaluating the Causal Role of Gut Microbiota in Type 1 Diabetes and Its Possible Pathogenic Mechanisms. Front Endocrinol (Lausanne) 2020; 11: 125.
[http://dx.doi.org/10.3389/fendo.2020.00125] [PMID: 32265832]
[275]
Murri M, Leiva I, Gomez-Zumaquero JM, et al. Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case-control study. BMC Med 2013; 11: 46.
[http://dx.doi.org/10.1186/1741-7015-11-46] [PMID: 23433344]
[276]
Leiva-Gea I, Sánchez-Alcoholado L, Martín-Tejedor B, et al. Gut microbiota differs in composition and functionality between children with type 1 diabetes and MODY2 and healthy control subjects: a case-control study. Diabetes Care 2018; 41(11): 2385-95.
[http://dx.doi.org/10.2337/dc18-0253] [PMID: 30224347]
[277]
Higuchi BS, Rodrigues N, Gonzaga MI, et al. Intestinal dysbiosis in autoimmune diabetes is correlated with poor gycemic control and increased interleukin-6: a pilot study. Front Immunol 2018; 9: 1689.
[http://dx.doi.org/10.3389/fimmu.2018.01689] [PMID: 30090100]
[278]
Zhu A, Chen J, Wu P, et al. Cationic polystyrene resolves nonalcoholic steatohepatitis, obesity, and metabolic disorders by promoting eubiosis of gut microbiota and decreasing endotoxemia. Diabetes 2017; 66(8): 2137-43.
[http://dx.doi.org/10.2337/db17-0070] [PMID: 28446519]
[279]
Tao YW, Gu YL, Mao XQ, Zhang L, Pei YF. Effects of probiotics on type II diabetes mellitus: a meta-analysis. J Transl Med 2020; 18(1): 30. [published correction appears in J Transl Med. 2020 Feb 28;18(1):105].
[http://dx.doi.org/10.1186/s12967-020-02213-2] [PMID: 31952517]
[280]
Verma A, Xu K, Du T, et al. Expression of human ACE2 in lactobacillus and beneficial effects in diabetic retinopathy in mice. Mol Ther Methods Clin Dev 2019; 14: 161-70. [published correction appears in Mol Ther Methods Clin Dev. 2020 Feb 25;17:400].
[http://dx.doi.org/10.1016/j.omtm.2019.06.007] [PMID: 31380462]
[281]
Saxena A. Probiotics as a potential alternative for relieving peripheral neuropathies: a case for guillain-barré syndrome. Front Microbiol 2016; 6: 1497.
[http://dx.doi.org/10.3389/fmicb.2015.01497] [PMID: 26779152]
[282]
Sabico S, Al-Mashharawi A, Al-Daghri NM, et al. Effects of a 6- month multi-strain probiotics supplementation in endotoxemic, inflammatory and cardiometabolic status of T2DM patients: A randomized, double-blind, placebo-controlled trial. Clin Nutr 2019; 38(4): 1561-9.
[http://dx.doi.org/10.1016/j.clnu.2018.08.009] [PMID: 30170781]
[283]
Ho J, Nicolucci AC, Virtanen H, et al. Effect of prebiotic on microbiota, intestinal permeability, and glycemic control in children with type 1 diabetes. J Clin Endocrinol Metab 2019; 104(10): 4427-40.
[http://dx.doi.org/10.1210/jc.2019-00481] [PMID: 31188437]
[284]
Nabhani Z, Hezaveh SJG, Razmpoosh E, Asghari-Jafarabadi M, Gargari BP. The effects of synbiotic supplementation on insulin resistance/sensitivity, lipid profile and total antioxidant capacity in women with gestational diabetes mellitus: A randomized double blind placebo controlled clinical trial. Diabetes Res Clin Pract 2018; 138: 149-57.
[http://dx.doi.org/10.1016/j.diabres.2018.02.008] [PMID: 29432772]
[285]
den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res 2013; 54(9): 2325-40.
[http://dx.doi.org/10.1194/jlr.R036012] [PMID: 23821742]

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