Abstract
Cardiovascular complications and renal disease is the growing cause of mortality in patients with diabetes. The subversive complications of diabetes such as hyperglycemia, hyperlipidemia and insulin resistance lead to an increase in the risk of myocardial infarction (MI), stroke, heart failure (HF) as well as chronic kidney disease (CKD). Among the commercially available anti-hyperglycemic agents, incretin-based medications appear to be safe and effective in the treatment of type 2 diabetes mellitus (T2DM) and associated cardiovascular and renal disease. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been shown to be fruitful in reducing HbA1c, blood glucose, lipid profile, and body weight in diabetic patients. Several preclinical and clinical studies revealed the safety, efficacy, and preventive advantages of GLP-1RAs against diabetes- induced cardiovascular and kidney disease. Data from cardio-renal outcome trials had highlighted that GLP-1RAs protected people with established CKD from significant cardiovascular disease, lowered the likelihood of hospitalization for heart failure (HHF), and lowered all-cause mortality. They also had a positive effect on people with end-stage renal disease (ESRD) and CKD. Beside clinical outcomes, GLP-1RAs reduced oxidative stress, inflammation, fibrosis, and improved lipid profile pre-clinically in diabetic models of cardiomyopathy and nephropathy that demonstrated the cardio-protective and reno-protective effect of GLP-1RAs. In this review, we have focused on the recent clinical and preclinical outcomes of GLP-1RAs as cardio-protective and reno-protective agents as GLP-1RAs medications have been demonstrated to be more effective in treating T2DM and diabetes-induced cardiovascular and renal disease than currently available treatments in clinics, without inducing hypoglycemia or weight gain.
[1]
Prabhakar PK. Pathophysiology of secondary complications of diabetes mellitus. Pathophysiology 2016; 9(1)
[2]
Roep BO, Thomaidou S, van Tienhoven R, Zaldumbide A. Type 1 diabetes mellitus as a disease of the β-cell (do not blame the immune system?). Nat Rev Endocrinol 2021; 17(3): 150-61.
[http://dx.doi.org/10.1038/s41574-020-00443-4] [PMID: 33293704]
[http://dx.doi.org/10.1038/s41574-020-00443-4] [PMID: 33293704]
[3]
Barrett EJ, Liu Z, Khamaisi M, et al. Diabetic microvascular disease: An endocrine society scientific statement. J Clin Endocrinol Metab 2017; 102(12): 4343-410.
[http://dx.doi.org/10.1210/jc.2017-01922] [PMID: 29126250]
[http://dx.doi.org/10.1210/jc.2017-01922] [PMID: 29126250]
[4]
Vesa CM, Popa L, Popa AR, et al. Current data regarding the relationship between type 2 diabetes mellitus and cardiovascular risk factors. Diagnostics 2020; 10(5): 314.
[http://dx.doi.org/10.3390/diagnostics10050314] [PMID: 32429441]
[http://dx.doi.org/10.3390/diagnostics10050314] [PMID: 32429441]
[5]
Gheith O, Farouk N, Nampoory N, Halim MA, Al-Otaibi T. Diabetic kidney disease: World wide difference of prevalence and risk factors. J Nephropharmacol 2015; 5(1): 49-56.
[PMID: 28197499]
[PMID: 28197499]
[6]
Koye DN, Magliano DJ, Nelson RG, Pavkov ME. The global epidemiology of diabetes and kidney disease. Adv Chronic Kidney Dis 2018; 25(2): 121-32.
[http://dx.doi.org/10.1053/j.ackd.2017.10.011] [PMID: 29580576]
[http://dx.doi.org/10.1053/j.ackd.2017.10.011] [PMID: 29580576]
[7]
Ma CX, Ma XN, Guan CH, Li YD, Mauricio D, Fu SB. Cardiovascular disease in type 2 diabetes mellitus: Progress toward personalized management. Cardiovasc Diabetol 2022; 21(1): 74.
[http://dx.doi.org/10.1186/s12933-022-01516-6] [PMID: 35568946]
[http://dx.doi.org/10.1186/s12933-022-01516-6] [PMID: 35568946]
[8]
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]
[http://dx.doi.org/10.1053/j.ackd.2014.03.003] [PMID: 24780455]
[9]
Gilbert MP, Pratley RE. GLP-1 analogs and DPP-4 inhibitors in type 2 diabetes therapy: Review of head-to-head clinical trials. Front Endocrinol 2020; 11: 178.
[http://dx.doi.org/10.3389/fendo.2020.00178] [PMID: 32308645]
[http://dx.doi.org/10.3389/fendo.2020.00178] [PMID: 32308645]
[10]
Knudsen LB, Lau J. The discovery and development of liraglutide and semaglutide. Front Endocrinol 2019; 10: 155.
[http://dx.doi.org/10.3389/fendo.2019.00155] [PMID: 31031702]
[http://dx.doi.org/10.3389/fendo.2019.00155] [PMID: 31031702]
[11]
Górriz JL, Soler MJ, Navarro-González JF, et al. GLP-1 receptor agonists and diabetic kidney disease: A call of attention to nephrologists. J Clin Med 2020; 9(4): 947.
[http://dx.doi.org/10.3390/jcm9040947] [PMID: 32235471]
[http://dx.doi.org/10.3390/jcm9040947] [PMID: 32235471]
[12]
Kawanami D, Takashi Y. GLP-1 receptor agonists in diabetic kidney disease: From clinical outcomes to mechanisms. Front Pharmacol 2020; 11: 967.
[http://dx.doi.org/10.3389/fphar.2020.00967] [PMID: 32694999]
[http://dx.doi.org/10.3389/fphar.2020.00967] [PMID: 32694999]
[13]
Rizzo M, Nikolic D, Patti AM, et al. GLP-1 receptor agonists and reduction of cardiometabolic risk: Potential underlying mechanisms. Biochim Biophys Acta Mol Basis Dis 2018; 1864(9): 2814-21.
[http://dx.doi.org/10.1016/j.bbadis.2018.05.012] [PMID: 29778663]
[http://dx.doi.org/10.1016/j.bbadis.2018.05.012] [PMID: 29778663]
[14]
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.
[http://dx.doi.org/10.1016/S2213-8587(19)30249-9] [PMID: 31422062]
[http://dx.doi.org/10.1016/S2213-8587(19)30249-9] [PMID: 31422062]
[15]
Müller TD, Finan B, Bloom SR, et al. Glucagon-like peptide 1 (GLP-1). Mol Metab 2019; 30: 72-130.
[http://dx.doi.org/10.1016/j.molmet.2019.09.010] [PMID: 31767182]
[http://dx.doi.org/10.1016/j.molmet.2019.09.010] [PMID: 31767182]
[16]
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]
[http://dx.doi.org/10.1053/j.gastro.2007.03.054] [PMID: 17498508]
[17]
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]
[http://dx.doi.org/10.1016/j.biopha.2018.08.088] [PMID: 30372907]
[18]
Nadkarni P, Chepurny OG, Holz GG. Regulation of glucose homeostasis by GLP-1. Prog Mol Biol Transl Sci 2014; 121: 23-65.
[http://dx.doi.org/10.1016/B978-0-12-800101-1.00002-8] [PMID: 24373234]
[http://dx.doi.org/10.1016/B978-0-12-800101-1.00002-8] [PMID: 24373234]
[19]
Davies MJ, Aroda VR, Collins BS, et al. Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2022; 45(11): 2753-86.
[http://dx.doi.org/10.2337/dci22-0034] [PMID: 36148880]
[http://dx.doi.org/10.2337/dci22-0034] [PMID: 36148880]
[20]
Bailey CJ, Day C. The future of new drugs for diabetes management. Diabetes Res Clin Pract 2019; 155: 107785.
[http://dx.doi.org/10.1016/j.diabres.2019.107785] [PMID: 31326453]
[http://dx.doi.org/10.1016/j.diabres.2019.107785] [PMID: 31326453]
[21]
Kodera R, Shikata K, Kataoka HU, et al. Glucagon-like peptide-1 receptor agonist ameliorates renal injury through its anti-inflammatory action without lowering blood glucose level in a rat model of type 1 diabetes. Diabetologia 2011; 54(4): 965-78.
[http://dx.doi.org/10.1007/s00125-010-2028-x] [PMID: 21253697]
[http://dx.doi.org/10.1007/s00125-010-2028-x] [PMID: 21253697]
[22]
Ishibashi Y, Nishino Y, Matsui T, Takeuchi M, Yamagishi S. Glucagon-like peptide-1 suppresses advanced glycation end product-induced monocyte chemoattractant protein-1 expression in mesangial cells by reducing advanced glycation end product receptor level. Metabolism 2011; 60(9): 1271-7.
[http://dx.doi.org/10.1016/j.metabol.2011.01.010] [PMID: 21388644]
[http://dx.doi.org/10.1016/j.metabol.2011.01.010] [PMID: 21388644]
[23]
Nikolaidis LA, Mankad S, Sokos GG, et al. Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation 2004; 109(8): 962-5.
[http://dx.doi.org/10.1161/01.CIR.0000120505.91348.58] [PMID: 14981009]
[http://dx.doi.org/10.1161/01.CIR.0000120505.91348.58] [PMID: 14981009]
[24]
Nathanson D, Ullman B, Löfström U, et al. Effects of intravenous exenatide in type 2 diabetic patients with congestive heart failure: A double-blind, randomised controlled clinical trial of efficacy and safety. Diabetologia 2012; 55(4): 926-35.
[http://dx.doi.org/10.1007/s00125-011-2440-x] [PMID: 22246377]
[http://dx.doi.org/10.1007/s00125-011-2440-x] [PMID: 22246377]
[25]
Bose AK, Mocanu MM, Carr RD, et al. Glucagon-like peptide 1 can directly protect the heart against ischemia/reperfusion injury. Diabetes 2005; 54(1): 146-51.
[http://dx.doi.org/10.2337/diabetes.54.1.146] [PMID: 15616022]
[http://dx.doi.org/10.2337/diabetes.54.1.146] [PMID: 15616022]
[26]
Timmers L, Henriques JPS, de Kleijn DPV, 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]
[http://dx.doi.org/10.1016/j.jacc.2008.10.033] [PMID: 19195607]
[27]
de Boer IH, Khunti K, Sadusky T, et al. Diabetes management in chronic kidney disease: A consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO). Diabetes Care 2022; 45(12): 3075-90.
[http://dx.doi.org/10.2337/dci22-0027] [PMID: 36189689]
[http://dx.doi.org/10.2337/dci22-0027] [PMID: 36189689]
[28]
de Boer IH, Caramori ML, Chan JCN, et al. Executive summary of the 2020 KDIGO Diabetes Management in CKD Guideline: Evidence-based advances in monitoring and treatment. Kidney Int 2020; 98(4): 839-48.
[http://dx.doi.org/10.1016/j.kint.2020.06.024] [PMID: 32653403]
[http://dx.doi.org/10.1016/j.kint.2020.06.024] [PMID: 32653403]
[29]
Tan Q, Akindehin SE, Orsso CE, et al. Recent advances in incretin-based pharmacotherapies for the treatment of obesity and diabetes. Front Endocrinol 2022; 13: 838410.
[http://dx.doi.org/10.3389/fendo.2022.838410] [PMID: 35299971]
[http://dx.doi.org/10.3389/fendo.2022.838410] [PMID: 35299971]
[30]
Kim W, Egan JM. The role of incretins in glucose homeostasis and diabetes treatment. Pharmacol Rev 2008; 60(4): 470-512.
[http://dx.doi.org/10.1124/pr.108.000604] [PMID: 19074620]
[http://dx.doi.org/10.1124/pr.108.000604] [PMID: 19074620]
[31]
Ruiten CC, der Aart-van der Beek AB, IJzerman RG, et al. Effect of exenatide twice daily and dapagliflozin, alone and in combination, on markers of kidney function in obese patients with type 2 diabetes: A prespecified secondary analysis of a randomized controlled clinical trial. Diabetes Obes Metab 2021; 23(8): 1851-8.
[http://dx.doi.org/10.1111/dom.14410] [PMID: 33908691]
[http://dx.doi.org/10.1111/dom.14410] [PMID: 33908691]
[32]
Aart - van der Beek AB, Raalte DH, Guja C, et al. Exenatide once weekly decreases urinary albumin excretion in patients with type 2 diabetes and elevated albuminuria: Pooled analysis of randomized active controlled clinical trials. Diabetes Obes Metab 2020; 22(9): 1556-66.
[http://dx.doi.org/10.1111/dom.14067] [PMID: 32329160]
[http://dx.doi.org/10.1111/dom.14067] [PMID: 32329160]
[33]
Muskiet MHA, Bunck MC, Heine RJ, et al. Exenatide twice-daily does not affect renal function or albuminuria compared to titrated insulin glargine in patients with type 2 diabetes mellitus: A post-hoc analysis of a 52-week randomised trial. Diabetes Res Clin Pract 2019; 153: 14-22.
[http://dx.doi.org/10.1016/j.diabres.2019.05.001] [PMID: 31078666]
[http://dx.doi.org/10.1016/j.diabres.2019.05.001] [PMID: 31078666]
[34]
Holman RR, Bethel MA, Mentz RJ, et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2017; 377(13): 1228-39.
[http://dx.doi.org/10.1056/NEJMoa1612917] [PMID: 28910237]
[http://dx.doi.org/10.1056/NEJMoa1612917] [PMID: 28910237]
[35]
Ding W, Chang W, Guo X, et al. Exenatide protects against cardiac dysfunction by attenuating oxidative stress in the diabetic mouse heart. Front Endocrinol 2019; 10: 202.
[http://dx.doi.org/10.3389/fendo.2019.00202] [PMID: 31024445]
[http://dx.doi.org/10.3389/fendo.2019.00202] [PMID: 31024445]
[36]
Laugero KD, Stonehouse AH, Guss S, Landry J, Vu C, Parkes DG. Exenatide improves hypertension in a rat model of the metabolic syndrome. Metab Syndr Relat Disord 2009; 7(4): 327-34.
[http://dx.doi.org/10.1089/met.2008.0095] [PMID: 19320558]
[http://dx.doi.org/10.1089/met.2008.0095] [PMID: 19320558]
[37]
Garczorz W, Gallego-Colon E, Kosowska A, et al. Exenatide exhibits anti-inflammatory properties and modulates endothelial response to tumor necrosis factor α-mediated activation. Cardiovasc Ther 2018; 36(2): e12317.
[http://dx.doi.org/10.1111/1755-5922.12317] [PMID: 29283509]
[http://dx.doi.org/10.1111/1755-5922.12317] [PMID: 29283509]
[38]
DeYoung MB, MacConell L, Sarin V, Trautmann M, Herbert P. Encapsulation of exenatide in poly-(D,L-lactide-co-glycolide) microspheres produced an investigational long-acting once-weekly formulation for type 2 diabetes. Diabetes Technol Ther 2011; 13(11): 1145-54.
[http://dx.doi.org/10.1089/dia.2011.0050] [PMID: 21751887]
[http://dx.doi.org/10.1089/dia.2011.0050] [PMID: 21751887]
[39]
Patti AM, Nikolic D, Magan-Fernandez A, et al. Exenatide once-weekly improves metabolic parameters, endothelial dysfunction and carotid intima-media thickness in patients with type-2 diabetes: An 8-month prospective study. Diabetes Res Clin Pract 2019; 149: 163-9.
[http://dx.doi.org/10.1016/j.diabres.2019.02.006] [PMID: 30759365]
[http://dx.doi.org/10.1016/j.diabres.2019.02.006] [PMID: 30759365]
[40]
Watanabe Y, Saisho Y, Inaishi J, et al. Efficacy and safety of once‐weekly exenatide after switching from twice‐daily exenatide in patients with type 2 diabetes. J Diabetes Investig 2020; 11(2): 382-8.
[http://dx.doi.org/10.1111/jdi.13146] [PMID: 31518492]
[http://dx.doi.org/10.1111/jdi.13146] [PMID: 31518492]
[41]
Wajcberg E. Amatur Amarah. Liraglutide in the management of type 2 diabetes. Drug Des Devel Ther 2010; 4: 279-90.
[http://dx.doi.org/10.2147/DDDT.S10180] [PMID: 21116334]
[http://dx.doi.org/10.2147/DDDT.S10180] [PMID: 21116334]
[42]
Buse JB, Rosenstock J, Sesti G, et al. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: A 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet 2009; 374(9683): 39-47.
[http://dx.doi.org/10.1016/S0140-6736(09)60659-0] [PMID: 19515413]
[http://dx.doi.org/10.1016/S0140-6736(09)60659-0] [PMID: 19515413]
[43]
Mann JFE, Fonseca V, Mosenzon O, et al. Effects of liraglutide versus placebo on cardiovascular events in patients with type 2 diabetes mellitus and chronic kidney disease. Circulation 2018; 138(25): 2908-18.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.036418] [PMID: 30566006]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.036418] [PMID: 30566006]
[44]
Verma S, Bhatt DL, Bain SC, et al. Effect of liraglutide on cardiovascular events in patients with type 2 diabetes mellitus and polyvascular disease: Results of the LEADER trial. Circulation 2018; 137(20): 2179-83.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.033898] [PMID: 29760228]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.033898] [PMID: 29760228]
[45]
Ripa RS, Zobel EH, von Scholten BJ, et al. Effect of liraglutide on arterial inflammation assessed as [ 18 F]FDG uptake in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial. Circ Cardiovasc Imaging 2021; 14(7): e012174.
[http://dx.doi.org/10.1161/CIRCIMAGING.120.012174] [PMID: 34187185]
[http://dx.doi.org/10.1161/CIRCIMAGING.120.012174] [PMID: 34187185]
[46]
Hallén J. Troponin for the estimation of infarct size: What have we learned? Cardiology 2012; 121(3): 204-12.
[http://dx.doi.org/10.1159/000337113] [PMID: 22516844]
[http://dx.doi.org/10.1159/000337113] [PMID: 22516844]
[47]
Nauck MA, Tornøe K, Rasmussen S, Treppendahl MB, Marso SP. Cardiovascular outcomes in patients who experienced a myocardial infarction while treated with liraglutide versus placebo in the LEADER trial. Diab Vasc Dis Res 2018; 15(5): 465-8.
[http://dx.doi.org/10.1177/1479164118783935] [PMID: 29947247]
[http://dx.doi.org/10.1177/1479164118783935] [PMID: 29947247]
[48]
Chen P, Shi X, Xu X, et al. Liraglutide ameliorates early renal injury by the activation of renal FoxO1 in a type 2 diabetic kidney disease rat model. Diabetes Res Clin Pract 2018; 137: 173-82.
[http://dx.doi.org/10.1016/j.diabres.2017.09.006] [PMID: 29355652]
[http://dx.doi.org/10.1016/j.diabres.2017.09.006] [PMID: 29355652]
[49]
Ougaard ME, Sembach FE, Jensen HE, Pyke C, Knudsen LB, Kvist PH. Liraglutide improves the kidney function in a murine model of chronic kidney disease. Nephron J 2020; 144(11): 595-606.
[http://dx.doi.org/10.1159/000509418] [PMID: 32877912]
[http://dx.doi.org/10.1159/000509418] [PMID: 32877912]
[50]
Zitman-Gal T, Einbinder Y, Ohana M, Katzav A, Kartawy A, Benchetrit S. Effect of liraglutide on the Janus kinase/signal transducer and transcription activator (JAK/STAT) pathway in diabetic kidney disease in db/db mice and in cultured endothelial cells. J Diabetes 2019; 11(8): 656-64.
[http://dx.doi.org/10.1111/1753-0407.12891] [PMID: 30575282]
[http://dx.doi.org/10.1111/1753-0407.12891] [PMID: 30575282]
[51]
Jimenez-Solem E, Rasmussen MH, Christensen M, Knop FK. Dulaglutide, a long-acting GLP-1 analog fused with an Fc antibody fragment for the potential treatment of type 2 diabetes. Curr Opin Mol Ther 2010; 12(6): 790-7.
[PMID: 21154170]
[PMID: 21154170]
[52]
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]
[http://dx.doi.org/10.1111/dom.12816] [PMID: 27766728]
[53]
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]
[http://dx.doi.org/10.1016/S2213-8587(18)30104-9] [PMID: 29910024]
[54]
Gerstein HC, Hart R, Colhoun HM, et al. The effect of dulaglutide on stroke: An exploratory analysis of the REWIND trial. Lancet Diabetes Endocrinol 2020; 8(2): 106-14.
[http://dx.doi.org/10.1016/S2213-8587(19)30423-1] [PMID: 31924562]
[http://dx.doi.org/10.1016/S2213-8587(19)30423-1] [PMID: 31924562]
[55]
Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): A double-blind, randomised placebo-controlled trial. Lancet 2019; 394(10193): 121-30.
[http://dx.doi.org/10.1016/S0140-6736(19)31149-3] [PMID: 31189511]
[http://dx.doi.org/10.1016/S0140-6736(19)31149-3] [PMID: 31189511]
[56]
Mahapatra MK, Karuppasamy M, Sahoo BM. Semaglutide, a glucagon like peptide-1 receptor agonist with cardiovascular benefits for management of type 2 diabetes. Rev Endocr Metab Disord 2022; 23(3): 521-39.
[http://dx.doi.org/10.1007/s11154-021-09699-1] [PMID: 34993760]
[http://dx.doi.org/10.1007/s11154-021-09699-1] [PMID: 34993760]
[57]
Sorli C, Harashima S, Tsoukas GM, et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): A double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Lancet Diabetes Endocrinol 2017; 5(4): 251-60.
[http://dx.doi.org/10.1016/S2213-8587(17)30013-X] [PMID: 28110911]
[http://dx.doi.org/10.1016/S2213-8587(17)30013-X] [PMID: 28110911]
[58]
Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2016; 375(19): 1834-44.
[http://dx.doi.org/10.1056/NEJMoa1607141] [PMID: 27633186]
[http://dx.doi.org/10.1056/NEJMoa1607141] [PMID: 27633186]
[59]
Husain M, Bain SC, Jeppesen OK, et al. Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk. Diabetes Obes Metab 2020; 22(3): 442-51.
[http://dx.doi.org/10.1111/dom.13955] [PMID: 31903692]
[http://dx.doi.org/10.1111/dom.13955] [PMID: 31903692]
[60]
Mosenzon O, Blicher TM, Rosenlund S, et al. Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): A placebo-controlled, randomised, phase 3a trial. Lancet Diabetes Endocrinol 2019; 7(7): 515-27.
[http://dx.doi.org/10.1016/S2213-8587(19)30192-5] [PMID: 31189517]
[http://dx.doi.org/10.1016/S2213-8587(19)30192-5] [PMID: 31189517]
[61]
Perkovic V, Bain S, Bakris G, et al. FP483 Effects of semaglutide and liraglutide on urinary Albumin-To-Creatinine Ratio (UACR) - A pooled analysis of sustain 6 and leader. Nephrol Dial Transplant 2019; 34(S1)
[62]
Edelman SV, Polonsky WH. Type 2 diabetes in the real world: The elusive nature of glycemic control. Diabetes Care 2017; 40(11): 1425-32.
[http://dx.doi.org/10.2337/dc16-1974] [PMID: 28801473]
[http://dx.doi.org/10.2337/dc16-1974] [PMID: 28801473]
[63]
Del Prato S, Kang J, Trautmann ME, et al. Efficacy and safety of once‐monthly efpeglenatide in patients with type 2 diabetes: Results of a phase 2 placebo‐controlled, 16‐week randomized dose‐finding study. Diabetes Obes Metab 2020; 22(7): 1176-86.
[http://dx.doi.org/10.1111/dom.14020] [PMID: 32128957]
[http://dx.doi.org/10.1111/dom.14020] [PMID: 32128957]
[64]
Gerstein HC, Sattar N, Rosenstock J, et al. Cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes. N Engl J Med 2021; 385(10): 896-907.
[http://dx.doi.org/10.1056/NEJMoa2108269] [PMID: 34215025]
[http://dx.doi.org/10.1056/NEJMoa2108269] [PMID: 34215025]
[65]
Trautmann ME, CHOI IY, KIM JK. Preclinical effects of efpeglenatide, a long-acting glucagon-like peptide-1 receptor agonist, compared with liraglutide and dulaglutide. Diabetes 2018; 67(S1): 1098-P.
[http://dx.doi.org/10.2337/db18-1098-P]
[http://dx.doi.org/10.2337/db18-1098-P]
[66]
Pratley R, Kang J, Choi IY, et al. The effect of efpeglenatide on lipid profiles and overall metabolism in patients with type 2 diabetes and obese patients without diabetes. Diabetes 2018; 67 (Suppl. 1): 2300-PUB.
[http://dx.doi.org/10.2337/db18-2300-PUB]
[http://dx.doi.org/10.2337/db18-2300-PUB]
[67]
Rosenstock J, Reusch J, Bush M, Yang F, Stewart M. Potential of albiglutide, a long-acting GLP-1 receptor agonist, in type 2 diabetes: A randomized controlled trial exploring weekly, biweekly, and monthly dosing. Diabetes Care 2009; 32(10): 1880-6.
[http://dx.doi.org/10.2337/dc09-0366] [PMID: 19592625]
[http://dx.doi.org/10.2337/dc09-0366] [PMID: 19592625]
[68]
Nauck MA, Stewart MW, Perkins C, et al. Efficacy and safety of once-weekly GLP-1 receptor agonist albiglutide (HARMONY 2): 52 week primary endpoint results from a randomised, placebo-controlled trial in patients with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetologia 2016; 59(2): 266-74.
[http://dx.doi.org/10.1007/s00125-015-3795-1] [PMID: 26577795]
[http://dx.doi.org/10.1007/s00125-015-3795-1] [PMID: 26577795]
[69]
Rosenstock J, NINO AI, SOFFER J. Near-normoglycemia, with meaningful discontinuations of prandial insulin, by adding weekly Albiglutide (Albi) to uncontrolled basal/bolus insulintreated type 2 Diabetes (T2DM). Diabetes 2018; 67(S1): 1073-P.
[70]
Home PD, Ahrén B, Reusch JEB, et al. Three-year data from 5 HARMONY phase 3 clinical trials of albiglutide in type 2 diabetes mellitus: Long-term efficacy with or without rescue therapy. Diabetes Res Clin Pract 2017; 131: 49-60.
[http://dx.doi.org/10.1016/j.diabres.2017.06.013] [PMID: 28683300]
[http://dx.doi.org/10.1016/j.diabres.2017.06.013] [PMID: 28683300]
[71]
Hernandez AF, Green JB, Janmohamed S, et al. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): A double-blind, randomised placebo-controlled trial. Lancet 2018; 392(10157): 1519-29.
[http://dx.doi.org/10.1016/S0140-6736(18)32261-X] [PMID: 30291013]
[http://dx.doi.org/10.1016/S0140-6736(18)32261-X] [PMID: 30291013]
[72]
Anderson SL, Trujillo JM. Lixisenatide in type 2 diabetes: Latest evidence and clinical usefulness. Ther Adv Chronic Dis 2016; 7(1): 4-17.
[http://dx.doi.org/10.1177/2040622315609312] [PMID: 26770666]
[http://dx.doi.org/10.1177/2040622315609312] [PMID: 26770666]
[73]
Muskiet MHA, Tonneijck L, Huang Y, et al. Lixisenatide and renal outcomes in patients with type 2 diabetes and acute coronary syndrome: An exploratory analysis of the ELIXA randomised, placebo-controlled trial. Lancet Diabetes Endocrinol 2018; 6(11): 859-69.
[http://dx.doi.org/10.1016/S2213-8587(18)30268-7] [PMID: 30292589]
[http://dx.doi.org/10.1016/S2213-8587(18)30268-7] [PMID: 30292589]
[74]
Pfeffer MA, Claggett B, Diaz R, et al. 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]
[http://dx.doi.org/10.1056/NEJMoa1509225] [PMID: 26630143]
[75]
Rayner CK, Watson LE, Phillips LK, et al. Effects of sustained treatment with lixisenatide on gastric emptying and postprandial glucose metabolism in type 2 diabetes: A randomized controlled trial. Diabetes Care 2020; 43(8): 1813-21.
[http://dx.doi.org/10.2337/dc20-0190] [PMID: 32471908]
[http://dx.doi.org/10.2337/dc20-0190] [PMID: 32471908]
[76]
Abdel-latif RG, Ahmed AF, Heeba GH. Low-dose lixisenatide protects against early-onset nephropathy induced in diabetic rats. Life Sci 2020; 263: 118592.
[http://dx.doi.org/10.1016/j.lfs.2020.118592] [PMID: 33065146]
[http://dx.doi.org/10.1016/j.lfs.2020.118592] [PMID: 33065146]
[77]
Min T, Bain SC. The role of tirzepatide, Dual GIP and GLP-1 receptor agonist, in the management of type 2 diabetes: The SURPASS clinical trials. Diabetes Ther 2021; 12(1): 143-57.
[http://dx.doi.org/10.1007/s13300-020-00981-0] [PMID: 33325008]
[http://dx.doi.org/10.1007/s13300-020-00981-0] [PMID: 33325008]
[78]
Rosenstock J, Wysham C, Frías JP, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): A double-blind, randomised, phase 3 trial. Lancet 2021; 398(10295): 143-55.
[http://dx.doi.org/10.1016/S0140-6736(21)01324-6] [PMID: 34186022]
[http://dx.doi.org/10.1016/S0140-6736(21)01324-6] [PMID: 34186022]
[79]
Wilson JM, Lin Y, Luo MJ, et al. The dual glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide‐1 receptor agonist tirzepatide improves cardiovascular risk biomarkers in patients with type 2 diabetes: A p ost hoc analysis. Diabetes Obes Metab 2022; 24(1): 148-53.
[http://dx.doi.org/10.1111/dom.14553] [PMID: 34542221]
[http://dx.doi.org/10.1111/dom.14553] [PMID: 34542221]
[80]
Del Prato S, Kahn SE, Pavo I, et al. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): A randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet 2021; 398(10313): 1811-24.
[http://dx.doi.org/10.1016/S0140-6736(21)02188-7] [PMID: 34672967]
[http://dx.doi.org/10.1016/S0140-6736(21)02188-7] [PMID: 34672967]
[81]
Lee MMY, Ghouri N, McGuire DK, Rutter MK, Sattar N. Meta-analyses of results from randomized outcome trials comparing cardiovascular effects of SGLT2is and GLP-1RAs in Asian versus white patients with and without type 2 diabetes. Diabetes Care 2021; 44(5): 1236-41.
[http://dx.doi.org/10.2337/dc20-3007] [PMID: 33707305]
[http://dx.doi.org/10.2337/dc20-3007] [PMID: 33707305]
[82]
Singh AK, Shah VN. Cardio-renal benefits of GLP-1 receptor agonists vs. SGLT-2 inhibitors in type 2 diabetes: Are they juxtaposed? Clinic Diabetol 2022; 11(4): 215-21.
[http://dx.doi.org/10.5603/DK.a2022.0037]
[http://dx.doi.org/10.5603/DK.a2022.0037]
[83]
Baviera M, Foresta A, Colacioppo P, et al. Effectiveness and safety of GLP-1 receptor agonists versus SGLT-2 inhibitors in type 2 diabetes: An Italian cohort study. Cardiovasc Diabetol 2022; 21(1): 162.
[http://dx.doi.org/10.1186/s12933-022-01572-y] [PMID: 35999556]
[http://dx.doi.org/10.1186/s12933-022-01572-y] [PMID: 35999556]
[84]
Drucker DJ. The cardiovascular biology of glucagon-like peptide-1. Cell Metab 2016; 24(1): 15-30.
[http://dx.doi.org/10.1016/j.cmet.2016.06.009] [PMID: 27345422]
[http://dx.doi.org/10.1016/j.cmet.2016.06.009] [PMID: 27345422]
[85]
Heerspink HJL, Perkins BA, Fitchett DH, Husain M, Cherney DZI. Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: Cardiovascular and kidney effects, potential mechanisms, and clinical applications. Circulation 2016; 134(10): 752-72.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.116.021887] [PMID: 27470878]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.116.021887] [PMID: 27470878]
[86]
Zelniker TA, Wiviott SD, Raz I, et al. Comparison of the effects of glucagon-like peptide receptor agonists and sodium-glucose cotransporter 2 inhibitors for prevention of major adverse cardiovascular and renal outcomes in type 2 diabetes mellitus: Systematic review and meta-analysis of cardiovascular outcomes trials. Circulation 2019; 139(17): 2022-31.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.038868] [PMID: 30786725]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.038868] [PMID: 30786725]
[87]
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]
[http://dx.doi.org/10.1152/physrev.00034.2006] [PMID: 17928588]
[88]
Merovci A, Solis-Herrera C, Daniele G, et al. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. J Clin Invest 2014; 124(2): 509-14.
[http://dx.doi.org/10.1172/JCI70704] [PMID: 24463448]
[http://dx.doi.org/10.1172/JCI70704] [PMID: 24463448]
[89]
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]
[http://dx.doi.org/10.1172/JCI72227] [PMID: 24463454]
[90]
Martinez R, Al-Jobori H, Ali AM, et al. Endogenous glucose production and hormonal changes in response to canagliflozin and liraglutide combination therapy. Diabetes 2018; 67(6): 1182-9.
[http://dx.doi.org/10.2337/db17-1278] [PMID: 29602791]
[http://dx.doi.org/10.2337/db17-1278] [PMID: 29602791]
[91]
Ali AM, Martinez R, Al-Jobori H, et al. Combination therapy with canagliflozin plus liraglutide exerts additive effect on weight loss, but not on HbA1c, in patients with type 2 diabetes. Diabetes Care 2020; 43(6): 1234-41.
[http://dx.doi.org/10.2337/dc18-2460] [PMID: 32220916]
[http://dx.doi.org/10.2337/dc18-2460] [PMID: 32220916]
[92]
Singh AK, Singh R. Metabolic and cardiovascular benefits with combination therapy of SGLT-2 inhibitors and GLP-1 receptor agonists in type 2 diabetes. World J Cardiol 2022; 14(6): 329-42.
[http://dx.doi.org/10.4330/wjc.v14.i6.329] [PMID: 35979179]
[http://dx.doi.org/10.4330/wjc.v14.i6.329] [PMID: 35979179]
[93]
Dave CV, Kim SC, Goldfine AB, Glynn RJ, Tong A, Patorno E. Risk of cardiovascular outcomes in patients with type 2 diabetes after addition of SGLT2 inhibitors versus sulfonylureas to baseline GLP-1RA therapy. Circulation 2021; 143(8): 770-9.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.120.047965] [PMID: 33302723]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.120.047965] [PMID: 33302723]
[94]
Ikonomidis I, Pavlidis G, Thymis J, et al. Effects of glucagon‐like peptide‐1 receptor agonists, sodium‐glucose cotransporter‐2 inhibitors, and their combination on endothelial glycocalyx, arterial function, and myocardial work index in patients with type 2 diabetes mellitus after 12‐month treatment. J Am Heart Assoc 2020; 9(9): e015716.
[http://dx.doi.org/10.1161/JAHA.119.015716] [PMID: 32326806]
[http://dx.doi.org/10.1161/JAHA.119.015716] [PMID: 32326806]
[95]
Ahmann AJ, Capehorn M, Charpentier G, et al. Efficacy and safety of once-weekly semaglutide versus exenatide ER in subjects with type 2 diabetes (SUSTAIN 3): A 56-week, open-label, randomized clinical trial. Diabetes Care 2018; 41(2): 258-66.
[http://dx.doi.org/10.2337/dc17-0417] [PMID: 29246950]
[http://dx.doi.org/10.2337/dc17-0417] [PMID: 29246950]
[96]
Pratley R, Amod A, Hoff ST, et al. Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): A randomised, double-blind, phase 3a trial. Lancet 2019; 394(10192): 39-50.
[http://dx.doi.org/10.1016/S0140-6736(19)31271-1] [PMID: 31186120]
[http://dx.doi.org/10.1016/S0140-6736(19)31271-1] [PMID: 31186120]
[97]
Frias JP, Bonora E, Nevarez Ruiz L, et al. Efficacy and safety of dulaglutide 3.0 mg and 4.5 mg versus dulaglutide 1.5 mg in metformin-treated patients with type 2 diabetes in a randomized controlled trial (AWARD-11). Diabetes Care 2021; 44(3): 765-73.
[http://dx.doi.org/10.2337/dc20-1473] [PMID: 33397768]
[http://dx.doi.org/10.2337/dc20-1473] [PMID: 33397768]
[98]
Mentz RJ, Thompson VP, Aguilar D, et al. Effects of once-weekly exenatide on clinical outcomes in patients with preexisting cardiovascular disease. Circulation 2018; 138(22): 2576-8.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.036811] [PMID: 30571356]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.036811] [PMID: 30571356]
[99]
Rasmussen IKB, Zobel EH, Ripa RS, et al. Liraglutide reduces cardiac adipose tissue in type 2 diabetes: A secondary analysis of the LIRAFLAME randomized placebo‐controlled trial. Diabetes Obes Metab 2021; 23(12): 2651-9.
[http://dx.doi.org/10.1111/dom.14516] [PMID: 34387408]
[http://dx.doi.org/10.1111/dom.14516] [PMID: 34387408]
[100]
Wang L, Xin Q, Wang Y, et al. Efficacy and safety of liraglutide in type 2 diabetes mellitus patients complicated with coronary artery disease: A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res 2021; 171: 105765.
[http://dx.doi.org/10.1016/j.phrs.2021.105765] [PMID: 34252552]
[http://dx.doi.org/10.1016/j.phrs.2021.105765] [PMID: 34252552]
[101]
Evans LM, Mellbin L, Johansen P, Lawson J, Paine A, Sandberg A. A population‐adjusted indirect comparison of cardiovascular benefits of once‐weekly subcutaneous semaglutide and dulaglutide in the treatment of patients with type 2 diabetes, with or without established cardiovascular disease. Endocrinol Diabetes Metab 2021; 4(3): e00259.
[http://dx.doi.org/10.1002/edm2.259] [PMID: 34277983]
[http://dx.doi.org/10.1002/edm2.259] [PMID: 34277983]
[102]
Dagenais GR, Rydén L, Leiter LA, et al. Total cardiovascular or fatal events in people with type 2 diabetes and cardiovascular risk factors treated with dulaglutide in the REWIND trail: A post hoc analysis. Cardiovasc Diabetol 2020; 19(1): 199.
[http://dx.doi.org/10.1186/s12933-020-01179-1] [PMID: 33239067]
[http://dx.doi.org/10.1186/s12933-020-01179-1] [PMID: 33239067]
[103]
Yin W, Xu S, Wang Z, et al. Recombinant human GLP-1(rhGLP-1) alleviating renal tubulointestitial injury in diabetic STZ-induced rats. Biochem Biophys Res Commun 2018; 495(1): 793-800.
[http://dx.doi.org/10.1016/j.bbrc.2017.11.076] [PMID: 29137984]
[http://dx.doi.org/10.1016/j.bbrc.2017.11.076] [PMID: 29137984]
[104]
Tsai TH, Lee CH, Cheng CI, et al. Liraglutide inhibits endothelial-to-mesenchymal transition and attenuates neointima formation after endovascular injury in streptozotocin-induced diabetic mice. Cells 2019; 8(6): 589.
[http://dx.doi.org/10.3390/cells8060589] [PMID: 31207939]
[http://dx.doi.org/10.3390/cells8060589] [PMID: 31207939]
[105]
Qian P, Tian H, Wang Y, et al. A novel oral glucagon-like peptide 1 receptor agonist protects against diabetic cardiomyopathy via alleviating cardiac lipotoxicity induced mitochondria dysfunction. Biochem Pharmacol 2020; 182: 114209.
[http://dx.doi.org/10.1016/j.bcp.2020.114209] [PMID: 32860826]
[http://dx.doi.org/10.1016/j.bcp.2020.114209] [PMID: 32860826]
[106]
Taguchi K, Bessho N, Kaneko N, Okudaira K, Matsumoto T, Kobayashi T. Glucagon-like peptide-1 increased the vascular relaxation response via AMPK/Akt signaling in diabetic mice aortas. Eur J Pharmacol 2019; 865: 172776.
[http://dx.doi.org/10.1016/j.ejphar.2019.172776] [PMID: 31697935]
[http://dx.doi.org/10.1016/j.ejphar.2019.172776] [PMID: 31697935]
[107]
Sanada J, Obata A, Obata Y, et al. Dulaglutide exerts beneficial anti atherosclerotic effects in ApoE knockout mice with diabetes: The earlier, the better. Sci Rep 2021; 11(1): 1425.
[http://dx.doi.org/10.1038/s41598-020-80894-x] [PMID: 33446799]
[http://dx.doi.org/10.1038/s41598-020-80894-x] [PMID: 33446799]
[108]
Li Q, Lin Y, Wang S, Zhang L, Guo L. GLP-1 inhibits high-glucose-induced oxidative injury of vascular endothelial cells. Sci Rep 2017; 7(1): 8008.
[http://dx.doi.org/10.1038/s41598-017-06712-z] [PMID: 28808291]
[http://dx.doi.org/10.1038/s41598-017-06712-z] [PMID: 28808291]
[109]
Zhao T, Chen H, Xu F, et al. Liraglutide alleviates cardiac fibrosis through inhibiting P4hα-1 expression in STZ-induced diabetic cardiomyopathy. Acta Biochim Biophys Sin 2019; 51(3): 293-300.
[http://dx.doi.org/10.1093/abbs/gmy177] [PMID: 30883649]
[http://dx.doi.org/10.1093/abbs/gmy177] [PMID: 30883649]
[110]
Liljedahl L, Pedersen MH, McGuire JN, James P. The impact of the glucagon-like peptide 1 receptor agonist liraglutide on the streptozotocin-induced diabetic mouse kidney proteome. Physiol Rep 2019; 7(4): e13994.
[http://dx.doi.org/10.14814/phy2.13994] [PMID: 30806030]
[http://dx.doi.org/10.14814/phy2.13994] [PMID: 30806030]
[111]
Yamada S, Tanabe J, Ogura Y, et al. Renoprotective effect of GLP-1 receptor agonist, liraglutide, in early-phase diabetic kidney disease in spontaneously diabetic Torii fatty rats. Clin Exp Nephrol 2021; 25(4): 365-75.
[http://dx.doi.org/10.1007/s10157-020-02007-2] [PMID: 33409761]
[http://dx.doi.org/10.1007/s10157-020-02007-2] [PMID: 33409761]
[112]
Fang S, Cai Y, Lyu F, et al. Exendin-4 improves diabetic kidney disease in C57BL/6 mice independent of brown adipose tissue activation. J Diabetes Res 2020; 2020: 1-12.
[http://dx.doi.org/10.1155/2020/9084567] [PMID: 32090125]
[http://dx.doi.org/10.1155/2020/9084567] [PMID: 32090125]
