An evaluation of canagliflozin for the treatment of type 2 diabetes: an update

References

• 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.
   PubMed Web of Science ®Google Scholar
• Chatterjee S, Khunti K, Davies MJ. Type 2 diabetes. Lancet. 2017;389(10085):2239–2251.
   PubMed Web of Science ®Google Scholar
• Jitraknatee J, Ruengorn C, Nochaiwong S. Prevalence and risk factors of chronic kidney disease among type 2 diabetes patients: a cross-sectional study in primary care practice. Sci Rep. 2020;10(1):6205.
   PubMed Web of Science ®Google Scholar
• Kannel WB, McGee DL. Diabetes and cardiovascular disease. The Framingham study. JAMA 1979;241(19):2035–2038.
   PubMed Web of Science ®Google Scholar
• Echouffo-Tcheugui JB, Xu H, DeVore AD, et al. Temporal trends and factors associated with diabetes mellitus among patients hospitalized with heart failure: findings from get with the guidelines-heart failure registry. Am Heart J. 2016;182:9–20.
   PubMed Web of Science ®Google Scholar
• Ghezzi C, Loo DDF, Wright EM. Physiology of renal glucose handling via SGLT1, SGLT2 and GLUT2. Diabetologia. 2018;61(10):2087–2097.
   PubMed Web of Science ®Google Scholar
• Mamidi RN, Cuyckens F, Chen J, et al. Metabolism and excretion of canagliflozin in mice, rats, dogs, and humans. Drug Metab Dispos. 2014;42:903–916.
   PubMed Web of Science ®Google Scholar
• Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375(4):323–334.
   PubMed Web of Science ®Google Scholar
• Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–2128.
   PubMed Web of Science ®Google Scholar
• Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380(4):347–357.
   PubMed Web of Science ®Google Scholar
• Mosenzon O, Wiviott SD, Cahn A, et al. Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE-TIMI 58 randomised trial. Lancet Diabetes Endocrinol. 2019;7(8):606–617.
   PubMed Web of Science ®Google Scholar
• Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7): 644–657.
   PubMed Web of Science ®Google Scholar
• Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380(24): 2295–2306.
   PubMed Web of Science ®Google Scholar
• Rosenthal N, Meininger G, Ways K, et al. Canagliflozin: a sodium glucose co-transporter 2 inhibitor for the treatment of type 2 diabetes mellitus. Ann N Y Acad Sci. 2015;1358(1):28–43.
   PubMed Web of Science ®Google Scholar
• Najafian M, Jahromi MZ, Nowroznejhad MJ, et al. Phloridzin reduces blood glucose levels and improves lipids metabolism in streptozotocin-induced diabetic rats. Mol Biol Rep. 2012;39(5):5299–5306.
   PubMed Web of Science ®Google Scholar
• Chow W, Miyasato G, Kokkotos FK. Real-world canagliflozin utilization: glycemic control among patients with type 2 diabetes mellitus-a multi-database synthesis. Clin Ther. 2016;38(9):2071–2082.
   PubMed Web of Science ®Google Scholar
• 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):587–597.
   PubMed Web of Science ®Google Scholar
• Kidokoro K, Cherney DZI, Bozovic A, et al. Evaluation of glomerular hemodynamic function by empagliflozin in diabetic mice using in vivo imaging. Circulation. 2019;140(4):303–315.
   PubMed Web of Science ®Google Scholar
• Tanaka H, Takano K, Iijima H, et al. Factors affecting canagliflozin-induced transient urine volume increase in patients with type 2 diabetes mellitus. Adv Ther. 2017;34(2):436–451.
   PubMed Web of Science ®Google Scholar
• Wilcox CS, Shen W, Boulton DW, et al. Interaction between the sodium-glucose-linked transporter 2 inhibitor dapagliflozin and the loop diuretic bumetanide in normal human subjects. J Am Heart Assoc. 2018;7(4):e007046.
   PubMed Web of Science ®Google Scholar
• Heerspink HJL, de Zeeuw D, Wie L, et al. Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes. Diabetes Obes Metab. 2013;15(9):853–862.
   PubMed Web of Science ®Google Scholar
• Hallow KM, Helmlinger G, Greasley PJ, et al. Why do SGLT2 inhibitors reduce heart failure hospitalization? A differential volume regulation hypothesis. Diabetes Obes Metab. 2018;20(3):479–487.
   PubMed Web of Science ®Google Scholar
• Scholtes RA, Muskiet MHA, van Baar MJB, et al. Natriuretic effect of two weeks of dapagliflozin treatment in patients with type 2 diabetes and preserved kidney function during standardized sodium intake: results of the DAPASALT trial. Diabetes Care. 2021;44(2):440–447.
   PubMed Web of Science ®Google Scholar
• Mordi NA, Mordi IR, Singh JS, et al. Renal and cardiovascular effects of SGLT2 inhibition in combination with loop diuretics in patients with type 2 diabetes and chronic heart failure: the RECEDE-CHF trial. Circulation. 2020;142(18):1713–1724.
   PubMed Web of Science ®Google Scholar
• Santos-Gallego CG, Vargas-Delgado AP, Requena-Ibanez JA, et al. Randomized trial of empagliflozin in nondiabetic patients with heart failure and reduced ejection fraction. J Am Coll Cardiol. 2021;77(3):243–255.
   PubMed Web of Science ®Google Scholar
• Nassif ME, Qintar M, Windsor SL, et al. Empagliflozin effects on pulmonary artery pressure in patients with heart failure: results from empagliflozin evaluation by measuring impact on hemodynamics in patients with heart failure (EMBRACE-HF) trial. Circulation. 2021;143(17):1673–1686.
   PubMed Web of Science ®Google Scholar
• Tomita I, Kume S, Sugahara S, et al. SGLT2 inhibition mediates protection from diabetic kidney disease by promoting ketone body-induced mTORC1 inhibition. Cell Metab. 2020;32(3):404–419.
   PubMed Web of Science ®Google Scholar
• Capozzi ME, Coch RW, Koech J, et al. The limited role of glucagon for ketogenesis during fasting or in response to SGLT2 inhibition. Diabetes. 2020;69(5):882–892.
   PubMed Web of Science ®Google Scholar
• Sternlicht H, Bakris GL. Blood pressure lowering and sodium-glucose co-transporter 2 inhibitors (SGLT2is): more than osmotic diuresis. Curr Hypertens Rep. 2019;21(2):12.
   PubMed Web of Science ®Google Scholar
• Tomita I, Kume S, Sugahara S, et al. SGLT2 inhibition mediates protection from diabetic kidney disease by promoting ketone body-induced mTORC1 inhibition. Cell Metab. 2020;32(3):404–419.
   PubMed Web of Science ®Google Scholar
• Ohara K, Masuda T, Murakami T, et al. Effects of the sodium-glucose cotransporter 2 inhibitor dapagliflozin on fluid distribution: a comparison study with furosemide and tolvaptan. Nephrology (Carlton). 2019;24(9):904–911.
   PubMed Web of Science ®Google Scholar
• Nielsen R, Møller N, Gormsen LC, et al. Cardiovascular effects of treatment with the ketone body 3-hydroxybutyrate in chronic heart failure patients. Circulation. 2019;139(18):2129–2141.
   PubMed Web of Science ®Google Scholar
• 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):1931–1944.
   PubMed Web of Science ®Google Scholar
• 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):862–873.
   PubMed Web of Science ®Google Scholar
• Ferrannini E, Mark M, Mayoux E. CV protection in the EMPA-REG OUTCOME trial: a “thrifty substrate” hypothesis. Diabetes Care. 2016;39(7):1108–1114.
   PubMed Web of Science ®Google Scholar
• 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):31–39.
   PubMed Web of Science ®Google Scholar
• Lo KB, Gul F, Ram P, et al. The effects of SGLT2 inhibitors on cardiovascular and renal outcomes in diabetic patients: a systematic review and meta-analysis. Cardiorenal Med. 2020;10(1):1–10.
   PubMed Web of Science ®Google Scholar
• Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436–1446.
   PubMed Web of Science ®Google Scholar
• American Diabetes Association. 9. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes—2020. Diabetes Care. 2020;43(Supplement 1):S98–S110.
   PubMed Web of Science ®Google Scholar
• Cosentino F, Grant PJ, Aboyans V, et al. ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2019;2020(41):255–323.
   Google Scholar
• Yokoyama H, Araki S-I, Kawai K, et al. The prognosis of patients with type 2 diabetes and nonalbuminuric diabetic kidney disease is not always poor: implication of the effects of coexisting macrovascular complications (JDDM 54). Diabetes Care. 2020;43(5):1102–1110.
   PubMed Web of Science ®Google Scholar
• Heerspink HJ, Desai M, Jardine M, et al. Canagliflozin slows progression of renal function decline independently of glycemic effects. J Am Soc Nephrol. 2017;28(1):368–375.
   PubMed Web of Science ®Google Scholar
• van Bommel EJM, Muskiet MHA, van Baar MJB, et al. The renal hemodynamic effects of the SGLT2 inhibitor dapagliflozin are caused by post-glomerular vasodilatation rather than pre-glomerular vasoconstriction in metformin-treated patients with type 2 diabetes in the randomized, double-blind RED trial. Kidney Int. 2020;97(1):202–212.
   PubMed Web of Science ®Google Scholar
• 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):722–726.
   PubMed Web of Science ®Google Scholar
• Chung YJ, Park KC, Tokar S, et al. Off target effects of SGLT2 blockers: empagliflozin does not inhibit Na+/H+ exchanger-1 or lower [Na+]i in the heart. Cardiovasc Res. 2020;cvaa323. https://doi.org/10.1093/cvr/cvaa323.
   Google Scholar
• Ferrannini E, Baldi S, Frascerra S, et al. Shift to fatty substrate utilization in response to sodium-glucose cotransporter 2 inhibition in subjects without diabetes and patients with type 2 diabetes. Diabetes. 2016;65(5):1190–1195.
   PubMed Web of Science ®Google Scholar
• Garcia-Ropero A, Santos-Gallego CG, Zafar MU, et al. Metabolism of the failing heart and the impact of SGLT2 inhibitors. Expert Opin Drug Metab Toxicol. 2019;15(4):275–285.
   PubMed Web of Science ®Google Scholar
• McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995–2008.
   PubMed Web of Science ®Google Scholar
• Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383(15):1413–1424.
   PubMed Web of Science ®Google Scholar
• Lee MMY, Brooksbank KJM, Wetherall K, et al. Effect of empagliflozin on left ventricular volumes in patients with type 2 diabetes, or prediabetes, and heart failure with reduced ejection fraction (SUGAR-DM-HF). Circulation. 2021;143(6):516–525.
   PubMed Web of Science ®Google Scholar
• Verma S, Mazer CD, Yan AT, et al. Effect of empagliflozin on left ventricular mass in patients with type 2 diabetes mellitus and coronary artery disease: the EMPA-HEART cardiolink-6 randomized clinical trial. Circulation. 2019;140(21):1693–1702.
   PubMed Web of Science ®Google Scholar
• 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):722–726.
   PubMed Web of Science ®Google Scholar
• Griffin M, Rao VS, Ivey-Miranda J, et al. Empagliflozin in heart failure: diuretic and cardiorenal effects. Circulation. 2020;142(11):1028–1039.
   PubMed Web of Science ®Google Scholar
• Kim SR, Lee SG, Kim SH, et al. SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease. Nat Commun. 2020;11(1):2127.
   PubMed Web of Science ®Google Scholar
• Pabel S, Wagner S, Bollenberg H, et al. Empagliflozin directly improves diastolic function in human heart failure. Eur J Heart Fail. 2018;20(12):1690–1700.
   PubMed Web of Science ®Google Scholar
• Hirasawa K, Namazi F, Milhorini Pio S, et al. Insufficient mitral leaflet remodeling in relation to annular dilation and risk of residual mitral regurgitation after mitraclip implantation. JACC Cardiovasc Imaging. 2021 Oct 28;14(4):SS1936–8.
   Web of Science ®Google Scholar
• Santos-Gallego CG, Requena-Ibanez JA, San Antonio R, et al. Empagliflozin ameliorates diastolic dysfunction and left ventricular fibrosis/stiffness in nondiabetic heart failure: a multimodality study. JACC Cardiovasc Imaging. 2021;14(2):393–407.
   PubMed Web of Science ®Google Scholar
• Anker SD, Butler J, Filippatos GS, et al. Evaluation of the effects of sodium-glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality in patients with chronic heart failure and a preserved ejection fraction: rationale for and design of the EMPEROR-preserved trial. Eur J Heart Fail. 2019;21(10):1279–1287.
   PubMed Web of Science ®Google Scholar
• ClinicalTrials.gov. Dapagliflozin Evaluation to improve the lives of patients with preserved ejection fraction heart failure. (DELIVER). 2020. [cited 2021 Mar 29]. https://clinicaltrials.gov/ct2/show/NCT03619213
   Google Scholar
• Spertus JA, Birmingham MC, Butler J, et al. Novel trial design: CHIEF-HF. Circ Heart Fail. 2021;14(3):e007767.
   PubMed Web of Science ®Google Scholar
• Kuriyama C, Xu JZ, Lee SP, et al. Analysis of the effect of canagliflozin on renal glucose reabsorption and progression of hyperglycemia in Zucker diabetic fatty rats. J Pharmacol Exp Ther. 2014;351(2):423–431.
   PubMed Web of Science ®Google Scholar
• Grempler R, Thomas L, Eckhardt M, et al. Empagliflozin, a novel selective sodium glucose cotransporter-2 (SGLT-2) inhibitor: characterisation and comparison with other SGLT-2 inhibitors. Diabetes Obes Metab. 2012;14(1):83–90.
   PubMed Web of Science ®Google Scholar
• Garcia-Ropero A, Badimon JJ, Santos-Gallego CG, et al. The pharmacokinetics and pharmacodynamics of SGLT2 inhibitors for type 2 diabetes mellitus: the latest developments. Expert Opin Drug Metab Toxicol. 2018;14(12):1287–1302.
   PubMed Web of Science ®Google Scholar
• Devineni D, Curtin CR, Marbury TC, et al. Effect of hepatic or renal impairment on the pharmacokinetics of canagliflozin, a sodium glucose co-transporter 2 inhibitor. Clin Ther. 2015;37(3):610–628.
   PubMed Web of Science ®Google Scholar
• Sha S, Devineni D, Ghosh A, et al. Pharmacodynamic effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, from a randomized study in patients with type 2 diabetes. PLoS One. 2014;9(8):e110069.
   PubMed Web of Science ®Google Scholar
• Devineni D, Polidori D. Clinical pharmacokinetic, pharmacodynamic, and drug-drug interaction profile of canagliflozin, a sodium-glucose Co-transporter 2 Inhibitor. Clin Pharmacokinet. 2015;54:1027–1041.
   PubMed Web of Science ®Google Scholar
• Nicolle LE, Capuano G, Ways K, et al. Effect of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, on bacteriuria and urinary tract infection in subjects with type 2 diabetes enrolled in a 12-week, phase 2 study. Curr Med Res Opin. 2012;28:1167–1171.
   PubMed Web of Science ®Google Scholar
• Cefalu WT, Leiter LA, Yoon KH, et al. Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet. 2013 Sep 14;382(9896):941–950.
   PubMed Web of Science ®Google Scholar
• Goda M, Yamakura T, Sasaki K, et al. Safety and efficacy of canagliflozin in elderly patients with type 2 diabetes mellitus: a 1-year post-marketing surveillance in Japan. Curr Med Res Opin. 2018 Feb;34(2):319–327.
   PubMed Web of Science ®Google Scholar
• Ryan PB, Buse JB, Schuemie MJ, et al. Comparative effectiveness of canagliflozin, SGLT2 inhibitors and non-SGLT2 inhibitors on the risk of hospitalization for heart failure and amputation in patients with type 2 diabetes mellitus: a real-world meta-analysis of 4 observational databases (OBSERVE-4D). Diabetes Obes Metab. 2018;20(11):2585–2597.
   PubMed Web of Science ®Google Scholar
• Matthews DR, Li Q, Perkovic V, et al. Effects of canagliflozin on amputation risk in type 2 diabetes: the CANVAS Program. Diabetologia. 2019;62(6):926–938.
   PubMed Web of Science ®Google Scholar
• Watts NB, Bilezikian JP, Usiskin K, et al. Effects of canagliflozin on fracture risk in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2016;101:157–166.
   PubMed Web of Science ®Google Scholar
• [cited Dec 10th]. http://www.accessdata.fda.gov/drugsatfda_docs/label/2020/204042s036lbl.pdf
   Google Scholar
• Karagiannis T, Bekiari E, Tsapas A, et al. Canagliflozin in the treatment of type 2 diabetes: an evidence-based review of its place in therapy. Core Evid. 2017;15(12):1–10.
   Web of Science ®Google Scholar
• Menne J, Dumann E, Haller H, et al. Acute kidney injury and adverse renal events in patients receiving SGLT2-inhibitors: a systematic review and meta-analysis. PLoS Med. 2019;16(12):e1002983.
   PubMed Web of Science ®Google Scholar
• Oshima M, Neuen BL, Jardine MJ, et al. Effects of canagliflozin on anaemia in patients with type 2 diabetes and chronic kidney disease: a post-hoc analysis from the CREDENCE trial. Lancet Diabetes Endocrinol. 2020;8:903–914.
   PubMed Web of Science ®Google Scholar
• Ghanim H, Abuaysheh S, Hejna J, et al. Dapagliflozin suppresses hepcidin and increases erythropoiesis. J Clin Endocrinol Metab. 2020;105(4):dgaa057.
   PubMed Web of Science ®Google Scholar
• Zhou Z, Lindley RI, Rådholm K, et al. Canagliflozin and stroke in type 2 diabetes mellitus. Stroke. 2019;50(2):396–404.
   PubMed Web of Science ®Google Scholar
• Mazidi M, Rezaie P, Gao HK, et al. Effect of sodium-glucose cotransport-2 inhibitors on blood pressure in people with type 2 diabetes mellitus: a systematic review and meta-analysis of 43 randomized control trials with 22 528 patients. Am Heart Assoc. 2017 May 25;6:e004007.
   PubMed Web of Science ®Google Scholar
• Zaccardi F, Webb DR, Htike ZZ, et al. Efficacy and safety of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes mellitus: systematic review and network meta-analysis. Diabetes Obes Metab. 2010;18:783–794.
   Web of Science ®Google Scholar