Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Effects of Glucagon-like Peptide-1 Receptor Agonists and Sodium-glucose Cotransporter 2 Inhibitors on Cardiorenal and Metabolic Outcomes in People Without Diabetes

Author(s): Athanasia K. Papazafiropoulou*, Andreas Melidonis and Stavros Antonopoulos

Volume 27, Issue 8, 2021

Published on: 09 September, 2020

Page: [1035 - 1042] Pages: 8

DOI: 10.2174/1381612826666200909142126

Price: $65

Open Access Journals Promotions 2
Abstract

During the last decade, the results of large-scale, randomized, clinical trials on newer antidiabetic agents, glucagon-like peptide-1 (GLP-1) receptor agonists and sodium glucose cotransporter type 2 (SGLT2) inhibitor, have been published showing promising findings on cardiovascular and renal outcomes. Besides improving glycemic control, GLP-1 receptor agonists have been shown to modify cardiovascular risk factors, such as insulin resistance, body weight, blood pressure (BP), and lipid profile. Additionally, SGLT2 inhibitors except for glycemic control have been shown to induce weight loss and decrease BP. However, there are limited data regarding their effect on patients without diabetes. Therefore, the aim of the present review is to summarize the existing literature data regarding the effects of newer antidiabetic therapies on patients without diabetes.

Keywords: Non-diabetic, SGLT2 inhibitors, GLP-1 receptor agonists, empagliflozin, dapagliflozin, canagliflozin, liraglutide, dulaglutide, exenatide, semaglutide.

« Previous Next »
[1]
Marso SP, Daniels GH, Brown-Frandsen K, et al. LEADER Steering Committee; LEADER Trial Investigators. 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]
[2]
Marso SP, Bain SC, Consoli A, et al. SUSTAIN-6 Investigators. SUSTAIN-6 Investigators. 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]
[3]
Gerstein HC, Colhoun HM, Dagenais GR, et al. REWIND Investigators. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial. Lancet 2019; 394(10193): 131-8.
[http://dx.doi.org/10.1016/S0140-6736(19)31150-X] [PMID: 31189509]
[4]
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]
[5]
Wanner C, Inzucchi SE, Lachin JM, et al. EMPA-REG OUTCOME Investigators. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 2016; 375(4): 323-34.
[http://dx.doi.org/10.1056/NEJMoa1515920] [PMID: 27299675]
[6]
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]
[7]
Anandhakrishnan A, Korbonits M. Glucagon-like peptide 1 in the pathophysiology and pharmacotherapy of clinical obesity. World J Diabetes 2016; 7(20): 572-98.
[http://dx.doi.org/10.4239/wjd.v7.i20.572] [PMID: 28031776]
[8]
Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol 2012; 8(12): 728-42.
[http://dx.doi.org/10.1038/nrendo.2012.140] [PMID: 22945360]
[9]
Edholm T, Degerblad M, Grybäck P, et al. Differential incretin effects of GIP and GLP-1 on gastric emptying, appetite, and insulin-glucose homeostasis. Neurogastroenterol Motil 2010; 22(11): 1191-1200, e315.
[http://dx.doi.org/10.1111/j.1365-2982.2010.01554.x] [PMID: 20584260]
[10]
Drucker DJ, Asa S. Glucagon gene expression in vertebrate brain. J Biol Chem 1988; 263(27): 13475-8.
[PMID: 2901414]
[11]
Turton MD, O’Shea D, Gunn I, et al. A role for glucagon-like peptide-1 in the central regulation of feeding. Nature 1996; 379(6560): 69-72.
[http://dx.doi.org/10.1038/379069a0] [PMID: 8538742]
[12]
Rodriquez de Fonseca F, Navarro M, Alvarez E, et al. Peripheral versus central effects of glucagon-like peptide-1 receptor agonists on satiety and body weight loss in Zucker obese rats. Metabolism 2000; 49(6): 709-17.
[http://dx.doi.org/10.1053/meta.2000.6251] [PMID: 10877194]
[13]
Holmes GM, Browning KN, Tong M, Qualls-Creekmore E, Travagli RA. Vagally mediated effects of glucagon-like peptide 1: in vitro and in vivo gastric actions. J Physiol 2009; 587(Pt 19): 4749-59.
[http://dx.doi.org/10.1113/jphysiol.2009.175067] [PMID: 19675064]
[14]
Buse JB, Klonoff DC, Nielsen LL, et al. Metabolic effects of two years of exenatide treatment on diabetes, obesity, and hepatic biomarkers in patients with type 2 diabetes: an interim analysis of data from the open-label, uncontrolled extension of three double-blind, placebo-controlled trials. Clin Ther 2007; 29(1): 139-53.
[http://dx.doi.org/10.1016/j.clinthera.2007.01.015] [PMID: 17379054]
[15]
DeFronzo RA, Ratner RE, Han J, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care 2005; 28(5): 1092-100.
[http://dx.doi.org/10.2337/diacare.28.5.1092] [PMID: 15855572]
[16]
Nelson P, Poon T, Guan X, Schnabel C, Wintle M, Fineman M. The incretin mimetic exenatide as a monotherapy in patients with type 2 diabetes. Diabetes Technol Ther 2007; 9(4): 317-26.
[http://dx.doi.org/10.1089/dia.2006.0024] [PMID: 17705687]
[17]
Dushay J, Gao C, Gopalakrishnan GS, et al. Short-term exenatide treatment leads to significant weight loss in a subset of obese women without diabetes. Diabetes Care 2012; 35(1): 4-11.
[http://dx.doi.org/10.2337/dc11-0931] [PMID: 22040840]
[18]
Vilsbøll T, Christensen M, Junker AE, Knop FK, Gluud LL. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ 2012; 344: d7771.
[http://dx.doi.org/10.1136/bmj.d7771] [PMID: 22236411]
[19]
Edwards CMB, Stanley SA, Davis R, et al. Exendin-4 reduces fasting and postprandial glucose and decreases energy intake in healthy volunteers. Am J Physiol Endocrinol Metab 2001; 281(1): E155-61.
[http://dx.doi.org/10.1152/ajpendo.2001.281.1.E155] [PMID: 11404233]
[20]
Verdich C, Flint A, Gutzwiller JP, et al. A meta-analysis of the effect of glucagon-like peptide-1 (7-36) amide on ad libitum energy intake in humans. J Clin Endocrinol Metab 2001; 86(9): 4382-9.
[PMID: 11549680]
[21]
Rosenstock J, Klaff LJ, Schwartz S, et al. Effects of exenatide and lifestyle modification on body weight and glucose tolerance in obese subjects with and without pre-diabetes. Diabetes Care 2010; 33(6): 1173-5.
[http://dx.doi.org/10.2337/dc09-1203] [PMID: 20332357]
[22]
Pinelli NR, Jantz A, Smith Z, et al. Effect of administration time of exenatide on satiety responses, blood glucose, and adverse events in healthy volunteers. J Clin Pharmacol 2011; 51(2): 165-72.
[http://dx.doi.org/10.1177/0091270010367653] [PMID: 20484613]
[23]
Su N, Li Y, Xu T, et al. Exenatide in obese or overweight patients without diabetes: A systematic review and meta-analyses of randomized controlled trials. Int J Cardiol 2016; 219: 293-300.
[http://dx.doi.org/10.1016/j.ijcard.2016.06.028] [PMID: 27343423]
[24]
Astrup A, Carraro R, Finer N, et al. NN8022-1807 Investigators. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int J Obes 2012; 36(6): 843-54.
[http://dx.doi.org/10.1038/ijo.2011.158] [PMID: 21844879]
[25]
Wadden TA, Hollander P, Klein S, et al. NN8022-1923 Investigators. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study. Int J Obes 2013; 37(11): 1443-51.
[http://dx.doi.org/10.1038/ijo.2013.120] [PMID: 23812094]
[26]
Pi-Sunyer X, Astrup A, Fujioka K, et al. SCALE Obesity and Prediabetes NN8022-1839 Study Group. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med 2015; 373(1): 11-22.
[http://dx.doi.org/10.1056/NEJMoa1411892] [PMID: 26132939]
[27]
le Roux CW, Astrup A, Fujioka K, et al. SCALE Obesity Prediabetes NN8022-1839 Study Group. 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial. Lancet 2017; 389(10077): 1399-409.
[http://dx.doi.org/10.1016/S0140-6736(17)30069-7] [PMID: 28237263]
[28]
Astrup A, Rössner S, Van Gaal L, et al. NN8022-1807 Study Group. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet 2009; 374(9701): 1606-16.
[http://dx.doi.org/10.1016/S0140-6736(09)61375-1] [PMID: 19853906]
[29]
Robert SA, Rohana AG, Shah SA, Chinna K, Wan Mohamud WN, Kamaruddin NA. Improvement in binge eating in non-diabetic obese individuals after 3 months of treatment with liraglutide - A pilot study. Obes Res Clin Pract 2015; 9(3): 301-4.
[http://dx.doi.org/10.1016/j.orcp.2015.03.005] [PMID: 25870084]
[30]
Blackman A, Foster GD, Zammit G, et al. Effect of liraglutide 3.0 mg in individuals with obesity and moderate or severe obstructive sleep apnea: the SCALE Sleep Apnea randomized clinical trial. Int J Obes 2016; 40(8): 1310-9.
[http://dx.doi.org/10.1038/ijo.2016.52] [PMID: 27005405]
[31]
Zhang P, Liu Y, Ren Y, Bai J, Zhang G, Cui Y. The efficacy and safety of liraglutide in the obese, non-diabetic individuals: a systematic review and meta-analysis. Afr Health Sci 2019; 19(3): 2591-9.
[PMID: 32127832]
[32]
Suhrs HE, Raft KF, Bové K, et al. Effect of liraglutide on body weight and microvascular function in non-diabetic overweight women with coronary microvascular dysfunction. Int J Cardiol 2019; 283: 28-34.
[http://dx.doi.org/10.1016/j.ijcard.2018.12.005] [PMID: 30773266]
[33]
Jorsal A, Kistorp C, Holmager P, et al. Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE)-a multicentre, double-blind, randomised, placebo-controlled trial. Eur J Heart Fail 2017; 19(1): 69-77.
[http://dx.doi.org/10.1002/ejhf.657] [PMID: 27790809]
[34]
Armstrong MJ, Gaunt P, Aithal GP, et al. LEAN trial team. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet 2016; 387(10019): 679-90.
[http://dx.doi.org/10.1016/S0140-6736(15)00803-X] [PMID: 26608256]
[35]
Sorli C, Harashima SI, 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]
[36]
Ahrén B, Masmiquel L, Kumar H, et al. Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial. Lancet Diabetes Endocrinol 2017; 5(5): 341-54.
[http://dx.doi.org/10.1016/S2213-8587(17)30092-X] [PMID: 28385659]
[37]
Aroda VR, Bain SC, Cariou B, et al. Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial. Lancet Diabetes Endocrinol 2017; 5(5): 355-66.
[http://dx.doi.org/10.1016/S2213-8587(17)30085-2] [PMID: 28344112]
[38]
O’Neil PM, Birkenfeld AL, McGowan B, et al. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet 2018; 392(10148): 637-49.
[http://dx.doi.org/10.1016/S0140-6736(18)31773-2] [PMID: 30122305]
[39]
Kushner RF, Calanna S, Davies M, et al. Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5. Obesity (Silver Spring) 2020; 28(6): 1050-61.
[http://dx.doi.org/10.1002/oby.22794] [PMID: 32441473]
[40]
NIH US Library of Medicine. Semaglutide Effects on Heart Disease and Stroke in Patients with overweight or obesity (SELECT). Available at: https://clinicaltrials.gov/ct2/show/NCT03574597
[41]
Seko Y, Sumida Y, Tanaka S, et al. Effect of dulaglitide for 12week in biopsy-proven NAFLD patients with type 2 diabetes in Japan. Hepatol Res 2017; 47: 1206-11.
[http://dx.doi.org/10.1111/hepr.12837] [PMID: 27917557]
[42]
de Leeuw AE, de Boer RA. Sodium-glucose cotransporter 2 inhibition: cardioprotection by treating diabetes-a translational viewpoint explaining its potential salutary effects. Eur Heart J Cardiovasc Pharmacother 2016; 2(4): 244-55.
[http://dx.doi.org/10.1093/ehjcvp/pvw009] [PMID: 27533948]
[43]
Al-Jobori H, Daniele G, Cersosimo E, et al. Empagliflozin and kinetics of renal glucose transport in healthy individuals and individuals with type 2 diabetes. Diabetes 2017; 66(7): 1999-2006.
[http://dx.doi.org/10.2337/db17-0100] [PMID: 28428225]
[44]
Lopaschuk GD, Verma S. Empagliflozin’s fuel hypothesis: not so soon. Cell Metab 2016; 24(2): 200-2.
[http://dx.doi.org/10.1016/j.cmet.2016.07.018] [PMID: 27508868]
[45]
Ferrannini E, Mark M, Mayoux E. CV protection in the EMPA-REG OUTCOME trial: a “thrifty substrate” hypothesis. Diabetes Care 2016; 39(7): 1108-14.
[http://dx.doi.org/10.2337/dc16-0330] [PMID: 27289126]
[46]
Baartscheer A, Schumacher CA, Wüst RC, et al. Empagliflozin decreases myocardial cytoplasmic Na+ through inhibition of the cardiac Na+/H+ exchanger in rats and rabbits. Diabetologia 2017; 60(3): 568-73.
[http://dx.doi.org/10.1007/s00125-016-4134-x] [PMID: 27752710]
[47]
Santos-Gallego CG, Requena-Ibanez JA, San Antonio R, et al. Empagliflozin Ameliorates Adverse Left Ventricular Remodeling in Nondiabetic Heart Failure by Enhancing Myocardial Energetics. J Am Coll Cardiol 2019; 73(15): 1931-44.
[http://dx.doi.org/10.1016/j.jacc.2019.01.056] [PMID: 30999996]
[48]
Connelly KA, Zhang Y, Visram A, et al. Empagliflozin Improves Diastolic Function in a Nondiabetic Rodent Model of Heart Failure With Preserved Ejection Fraction. JACC Basic Transl Sci 2019; 4(1): 27-37.
[http://dx.doi.org/10.1016/j.jacbts.2018.11.010] [PMID: 30847416]
[49]
Yurista SR, Silljé HHW, Oberdorf-Maass SU, et al. Sodium-glucose co-transporter 2 inhibition with empagliflozin improves cardiac function in non-diabetic rats with left ventricular dysfunction after myocardial infarction. Eur J Heart Fail 2019; 21(7): 862-73.
[http://dx.doi.org/10.1002/ejhf.1473] [PMID: 31033127]
[50]
Byrne NJ, Parajuli N, Levasseur JL, et al. Empagliflozin Prevents Worsening of Cardiac Function in an Experimental Model of Pressure Overload-Induced Heart Failure. JACC Basic Transl Sci 2017; 2(4): 347-54.
[http://dx.doi.org/10.1016/j.jacbts.2017.07.003] [PMID: 30062155]
[51]
Nikolaou PE, Efentakis P, Qourah FA, et al. Chronic Empaglifozin treatment reduces myocardial infarct size in non-diabetic mice through STAT-3 mediated protection on microvascular endothelial cells and reduction of oxidative stress. Antioxid Redox Signal 2020.
[http://dx.doi.org/10.1089/ars.2019.7923] [PMID: 32295413]
[52]
Yurista SR, Silljé HHW, van Goor H, et al. Effects of Sodium-Glucose Co-transporter 2 Inhibition with Empaglifozin on Renal Structure and Function in Non-diabetic Rats with Left Ventricular Dysfunction After Myocardial Infarction. Cardiovasc Drugs Ther 2020; 34(3): 311-21.
[http://dx.doi.org/10.1007/s10557-020-06954-6] [PMID: 32185580]
[53]
Lee HC, Shiou YL, Jhuo SJ, et al. The sodium-glucose co-transporter 2 inhibitor empagliflozin attenuates cardiac fibrosis and improves ventricular hemodynamics in hypertensive heart failure rats. Cardiovasc Diabetol 2019; 18(1): 45.
[http://dx.doi.org/10.1186/s12933-019-0849-6] [PMID: 30935417]
[54]
Abraham WT, Ponikowski P, Brueckmann M, et al. EMPERIAL Investigators and National Coordinators. Rationale and design of the EMPERIAL-Preserved and EMPERIAL-Reduced trials of empagliflozin in patients with chronic heart failure. Eur J Heart Fail 2019; 21(7): 932-42. l
[http://dx.doi.org/10.1002/ejhf.1486] [PMID: 31218819]
[55]
Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The Collaborative Study Group. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med 1993; 329(20): 1456-62.
[http://dx.doi.org/10.1056/NEJM199311113292004] [PMID: 8413456]
[56]
Brenner BM, Cooper ME, de Zeeuw D, et al. RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 345(12): 861-9.
[http://dx.doi.org/10.1056/NEJMoa011161] [PMID: 11565518]
[57]
Lewis EJ, Hunsicker LG, Clarke WR, et al. Collaborative Study Group. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001; 345(12): 851-60.
[http://dx.doi.org/10.1056/NEJMoa011303] [PMID: 11565517]
[58]
Cherney DZ, Perkins BA, Soleymanlou N, et al. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation 2014; 129(5): 587-97.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.113.005081] [PMID: 24334175]
[59]
Vallon V. Tubuloglomerular feedback and the control of glomerular filtration rate. News Physiol Sci 2003; 18: 169-74.
[http://dx.doi.org/10.1152/nips.01442.2003] [PMID: 12869618]
[60]
Fioretto P, Zambon A, Rossato M, Busetto L, Vettor R. SGLT2 inhibitors and the diabetic kidney. Diabetes Care 2016; 39(Suppl. 2): S165-71.
[http://dx.doi.org/10.2337/dcS15-3006] [PMID: 27440829]
[61]
Mudaliar S, Alloju S, Henry RR. Can a shift in fuel energetics explain the beneficial cardiorenal outcomes in the EMPA-REG OUTCOME study? A unifying hypothesis. Diabetes Care 2016; 39(7): 1115-22.
[http://dx.doi.org/10.2337/dc16-0542] [PMID: 27289124]
[62]
Kim S, Jo CH, Kim GH. Effects of empagliflozin on nondiabetic salt-sensitive hypertension in uninephrectomized rats. Hypertens Res 2019; 42(12): 1905-15.
[http://dx.doi.org/10.1038/s41440-019-0326-3] [PMID: 31537914]
[63]
Ma Q, Steiger S, Anders HJ. Sodium glucose transporter-2 inhibition has no renoprotective effects on non-diabetic chronic kidney disease. Physiol Rep 2017; 5(7): 5.
[http://dx.doi.org/10.14814/phy2.13228] [PMID: 28364032]
[64]
Hepprich M, Wiedemann SJ, Schelker BL, et al. Postprandial Hypoglycemia in Patients after Gastric Bypass Surgery Is Mediated by Glucose-Induced IL-1β. Cell Metab 2020; 31(4): 699-709.e5.
[http://dx.doi.org/10.1016/j.cmet.2020.02.013] [PMID: 32197070]
[65]
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]
[66]
McMurray JJV, Solomon SD, Inzucchi SE, et al. DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med 2019; 381(21): 1995-2008.
[http://dx.doi.org/10.1056/NEJMoa1911303] [PMID: 31535829]
[67]
Lee TM, Chang NC, Lin SZ. Dapagliflozin, a selective SGLT2 Inhibitor, attenuated cardiac fibrosis by regulating the macrophage polarization via STAT3 signaling in infarcted rat hearts. Free Radic Biol Med 2017; 104: 298-310.
[http://dx.doi.org/10.1016/j.freeradbiomed.2017.01.035] [PMID: 28132924]
[68]
Cassis P, Locatelli M, Cerullo D, et al. SGLT2 inhibitor dapagliflozin limits podocyte damage in proteinuric nondiabetic nephropathy. JCI Insight 2018; 3(15): 3.
[http://dx.doi.org/10.1172/jci.insight.98720] [PMID: 30089717]
[69]
Jaikumkao K, Pongchaidecha A, Chueakula N, et al. Dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, slows the progression of renal complications through the suppression of renal inflammation, endoplasmic reticulum stress and apoptosis in prediabetic rats. Diabetes Obes Metab 2018; 20(11): 2617-26.
[http://dx.doi.org/10.1111/dom.13441] [PMID: 29923295]
[70]
Rajasekeran H, Reich HN, Hladunewich MA, et al. Dapagliflozin in focal segmental glomerulosclerosis: a combined human-rodent pilot study. Am J Physiol Renal Physiol 2018; 314(3): F412-22.
[http://dx.doi.org/10.1152/ajprenal.00445.2017] [PMID: 29141939]
[71]
Heerspink HJL, Stefansson BV, Chertow GM, et al. DAPA-CKD Investigators. Rationale and protocol of the Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial. Nephrol Dial Transplant 2020; 35(2): 274-82.
[http://dx.doi.org/10.1093/ndt/gfz290] [PMID: 32030417]
[72]
Bolinder J, Ljunggren Ö, Kullberg J, et al. Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab 2012; 97(3): 1020-31.
[http://dx.doi.org/10.1210/jc.2011-2260] [PMID: 22238392]
[73]
Zhang M, Zhang L, Wu B, Song H, An Z, Li S. Dapagliflozin treatment for type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Diabetes Metab Res Rev 2014; 30(3): 204-21.
[http://dx.doi.org/10.1002/dmrr.2479] [PMID: 24115369]
[74]
Cefalu WT. Paradoxical insights into whole body metabolic adaptations following SGLT2 inhibition. J Clin Invest 2014; 124(2): 485-7.
[http://dx.doi.org/10.1172/JCI74297] [PMID: 24463446]
[75]
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]
[76]
Bertran E, Berlie HD, Nixon A, Jaber L. Does Dapagliflozin Affect Energy Intake and Appetite? A Randomized, Controlled Exploratory Study in Healthy Subjects. Clin Pharmacol Drug Dev 2019; 8(1): 119-25.
[http://dx.doi.org/10.1002/cpdd.461] [PMID: 29723443]
[77]
Lee SG, Lee SJ, Lee JJ, et al. Anti-Inflammatory Effect for Atherosclerosis Progression by Sodium-Glucose Cotransporter 2 (SGLT-2) Inhibitor in a Normoglycemic Rabbit Model. Korean Circ J 2020; 50(5): 443-57.
[http://dx.doi.org/10.4070/kcj.2019.0296] [PMID: 32153145]
[78]
Jardine MJ, Mahaffey KW, Neal B, et al. CREDENCE study investigators. The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) Study Rationale, Design, and Baseline Characteristics. Am J Nephrol 2017; 46(6): 462-72.
[http://dx.doi.org/10.1159/000484633] [PMID: 29253846]
[79]
Bays HE, Weinstein R, Law G, Canovatchel W. Canagliflozin: effects in overweight and obese subjects without diabetes mellitus. Obesity (Silver Spring) 2014; 22(4): 1042-9.
[http://dx.doi.org/10.1002/oby.20663] [PMID: 24227660]
[80]
Lim VG, Bell RM, Arjun S, Kolatsi-Joannou M, Long DA, Yellon DM. SGLT2 Inhibitor, Canagliflozin, Attenuates Myocardial Infarction in the Diabetic and Nondiabetic Heart. JACC Basic Transl Sci 2019; 4(1): 15-26.
[http://dx.doi.org/10.1016/j.jacbts.2018.10.002] [PMID: 30847415]
[81]
Hawley SA, Ford RJ, Smith BK, et al. The Na+/glucose cotransporter inhibitor canagliflozin activates AMPK by inhibiting mitochondrial function and increasing cellular AMP levels. Diabetes 2016; 65(9): 2784-94.
[http://dx.doi.org/10.2337/db16-0058] [PMID: 27381369]
[82]
Uthman L, Baartscheer A, Bleijlevens B, et al. Class effects of SGLT2 inhibitors in mouse cardiomyocytes and hearts: inhibition of Na+/H+ exchanger, lowering of cytosolic Na+ and vasodilation. Diabetologia 2018; 61(3): 722-6.
[http://dx.doi.org/10.1007/s00125-017-4509-7] [PMID: 29197997]
[83]
Han Y, Cho YE, Ayon R, et al. SGLT inhibitors attenuate NO-dependent vascular relaxation in the pulmonary artery but not in the coronary artery. Am J Physiol Lung Cell Mol Physiol 2015; 309(9): L1027-36.
[http://dx.doi.org/10.1152/ajplung.00167.2015] [PMID: 26361875]
[84]
El-Daly M, Pulakazhi Venu VK, Saifeddine M, et al. Hyperglycaemic impairment of PAR2-mediated vasodilation: Prevention by inhibition of aortic endothelial sodium-glucose-co-Transporter-2 and minimizing oxidative stress. Vascul Pharmacol 2018; 109: 56-71.
[http://dx.doi.org/10.1016/j.vph.2018.06.006] [PMID: 29908295]
[85]
Sayour AA, Korkmaz-Icöz S, Loganathan S, et al. Acute canagliflozin treatment protects against in vivo myocardial ischemia-reperfusion injury in non-diabetic male rats and enhances endothelium-dependent vasorelaxation. J Transl Med 2019; 17(1): 127.
[http://dx.doi.org/10.1186/s12967-019-1881-8] [PMID: 30992077]

Rights & Permissions Print Cite
Article Metrics
97
1
Wayfinder Image
Open Access Journals Promotions
World Antimicrobial Awareness Week
© 2024 Bentham Science Publishers | Privacy Policy