Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Research Article

The Possible Effects of Dapagliflozin on 12-derived Electrocardiogram in Patients with Type 2 Diabetes Mellitus

Author(s): Oğuz Akkuş, Gamze Akkuş* and Onur Kaypaklı

Volume 19, Issue 2, 2019

Page: [207 - 213] Pages: 7

DOI: 10.2174/1871530319666181218121508

Price: $65

Abstract

Background: Dapagliflozin, sodium glucose cotransporter 2 inhibitor, has potential side effects on electrolyte imbalance as it has diuretic effects which include decreasing glucose reabsorption, increasing glucosuria and natriuresis. We aimed to determine the possible effects of dapagliflozin on electrocardiogram (ECG) in patients with type 2 DM.

Material and Methods: This retrospective study consisted of 49 patients (25 female, 24 male). Patients who had inadequate glycemic control besides using several oral antidiabetics, subsequently endorsed with dapagliflozin, were included in the current study.

Results: Meantime interval from treatment initiation to control was 10.5 ± 5.03 weeks. Body mass index, glucose, HbA1C, eGFR, LDL-C, heart rate, systolic and diastolic blood pressures were found to be significantly lower at control admission (p<0.05). Creatinine and QT interval were significantly higher at control admission (p<0.05). Baseline Tpe duration and baseline Tpe/QT ratio were found to be significantly correlated with Tpe/QT difference (p<0.05). In linear regression analysis, baseline Tpe/QT ratio was found to be the sole independent predictor of Tpe/QT difference (p<0.05).

Conclusion: Initiation of dapagliflozin treatment seems to be safe, up to several months, in terms of serum electrolytes and ECG findings in patients with type 2 DM with a probable improvement.

Keywords: Type 2 diabetes mellitus, SGLT 2 inhibitor, electrolyte imbalance, 12-derived electrocardiogram, Tpe/QT, cardiovascular response.

Graphical Abstract
[1]
American Diabetes Association. standarts of medical care in diabetes. Erratum. Pharmacologic approaches to glycemic treatment. Sec. 8. I standards of medical care in diabetes-2017. Diabetes Care, 2017, 40(Suppl. 1), S64-S74.
[2]
American Diabetes Association. Standarts of medical care in diabetes. Erratum. Microvascular complications and foot care. Sec. 10. In standards of medical care in diabetes. Diabetes Care, 2017, 40(Suppl. 1), S88-S98.
[3]
American Diabetes Association. Standarts of medical care in diabetes. Glycemic targets. Diabetes Care, 2017, 40(Suppl. 1), S48-S56.
[4]
Yozgatli, K.; Lefrandt, J.D.; Noordzij, M.J.; Oomen, P.H.N.; Brouwer, T.; Jager, J.; Catro Cabezas, M.; Smit, A.J. Accumulation of advanced glycation end products is associated with macrovascular events and glycaemic control with microvascular complications in Type 2 diabetes mellitus. Diabet. Med., 2018. [Epub ahead of print].
[http://dx.doi.org/10.1111/dme.13651]
[5]
Emerging Risk Factors Collaboration. Sarwar, N.; Gao, P.; Seshasai, S.R.; Gobin, R.; Kaptoge, S.; Di Angelantonio, E.; Ingelsson, E.; Lawlor, D.A.; Selvin, E.; Stampfer, M.; Stehouwer, C.D.; Lewington, S.; Pennells, L.; Thompson, A.; Sattar, N.; White, I.R.; Ray, K.K.; Danesh, J. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: A collaborative meta-analysis of 102 prospective studies. Lancet, 2010, 375, 2215-2222.
[6]
da Silva, P.N.; da Conceição, R.A.; do Couto Maia, R.; de Castro Barbosa, M.L. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors: A new antidiabetic drug class. MedChemComm, 2018, 9, 1273-1281.
[7]
Cefalu, W.T.; Leiter, L.A.; de Bruin, T.W.; Gause-Nilsson, I.; Sugg, J.; Parikh, S.J. Dapagliflozin’s effects on glycemia and cardiovascular risk factors in high-risk patients with Type 2 diabetes: A 24-week, multicenter, randomized, double-blind, placebo-controlled study with a 28-week extension. Diabetes Care, 2015, 7, 1218-1227.
[8]
Minze, M.G.; Will, K.; Terrell, B.T.; Black, R.L.; Irons, B.K. Benefits of SGLT2 Inhibitors beyond glycemic control - A focus on metabolic, cardiovascular, and renal outcomes. Curr. Diabetes Rev., 2018, 14, 509-517.
[9]
Zinman, B.; Wanner, C.; Lachin, J.M.; Fitchett, D.; Bluhmki, E.; Hantel, S.; Mattheus, M.; Devins, T.; Johansen, O.E.; Woerle, H.J.; Broedl, U.C.; Inzucchi, S.E. EMPA-REG outcome Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N. Engl. J. Med., 2015, 373, 2117-2128.
[10]
Kohan, D.E.; Fioretto, P.; Tang, W.; List, J.F. Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control. Kidney Int., 2014, 85, 962-971.
[11]
Dawwas, G.K.; Smith, S.M.; Park, H. Cardiovascular outcomes of sodium glucose cotransporter-2 inhibitors in patients with type 2 diabetes. Diabetes Obes. Metab., 2019, 21, 28-36.
[12]
Hevia, C.J.; Antzelevitch, C.; Bárzaga, T.F.; Sánchez, D.M.; Balea, D.F.; Molina, Z.R.; Quiñones Pérez, M.A.; Fayad Rodríguez, Y. Tpeak-tend and tpeak-tend dispersion as risk factors for ventricular tachycardia/ventricular fibrillation in patients with the brugada syndrome. J. Am. Coll. Cardiol., 2006, 47, 1828-1834.
[13]
Shah, A.D.; Langenberg, C.; Rapsomaniki, E.; Denaxas, S.; Pujades-Rodriguez, M.; Gale, C.P.; Deanfield, J.; Smeeth, L.; Timmis, A.; Hemingway, H. Type 2 diabetes and incidence of cardiovascular diseases: A cohort study in 1.9 million people. Lancet Diabetes Endocrinol., 2015, 3, 105-113.
[14]
Bays, H. Sodium glucose co-transporter type 2 (SGLT2) inhibitors: Targeting the kidney to improve glycemic control in diabetes mellitus. Diabetes Ther., 2013, 4, 195-220.
[15]
Washburn, W.N.; Poucher, S.M. Differentiating sodium-glucose co-transporter-2 inhibitors in development for the treatment of type 2 diabetes mellitus. Expert Opin. Investig. Drugs, 2013, 4, 463-486.
[16]
Hach, T.; Gerich, J.; Salsali, A.; Kim, G.; Hantel, S.; Woerle, H.J.; Broedl, U.C. Empagliflozin improves glycaemic parameters and cardiovascular risk factors in patients with type 2 diabetes: Pooled data from four pivotal phase III trials. Diabetol. Stoffwechs., 2014, 9, 142.
[17]
Cherney, D.Z.; Perkins, B.A.; Soleymanlou, N.; Har, R.; Fagan, N.; Johansen, O.E.; Woerle, H.J.; von Eynatten, M.; Broedl, U.C. The effect of empagliflozin on arterial stiffness and heart rate variability in subjects with uncomplicated type 1 diabetes mellitus. Cardiovasc. Diabetol., 2014, 13, 28.
[18]
Terami, N.; Ogawa, D.; Tachibana, H.; Hatanaka, T.; Wada, J.; Nakatsuka, A.; Eguchi, J.; Horiguchi, C.S.; Nishii, N.; Yamada, H.; Takei, K.; Makino, H. Long-term treatment with the sodium glucose cotransporter 2 inhibitor, dapagliflozin, ameliorates glucose homeostasis and diabetic nephropathy in db/db mice. PLoS One, 2014, 9, e100777.
[19]
Matsushita, Y.; Ogawa, D.; Wada, J.; Yamamoto, N.; Shikata, K.; Sato, C.; Tachibana, H.; Toyota, N.; Makino, H. Activation of peroxisome proliferator-activated receptor delta inhibits streptozotocin-induced diabetic nephropathy through anti-inflammatory mechanisms in mice. Diabetes, 2011, 60, 960-968.
[20]
List, J.F.; Woo, V.; Morales, E.; Tang, W.; Fiedorek, F.T. Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care, 2009, 32, 650-657.
[21]
Klabunde, R.E. Cardiovascular physiology concepts 2th edition, Lippincott Williams Wilkins, Philadelphia, 2012, 2, 9-40. ;
[22]
Petrykiv, S.; Sjöström, C.D.; Greasley, P.J.; Xu, J.; Persson, F.; Heerspink, H.J.L. Differential effects of dapagliflozin on cardiovascular risk factors at varying degrees of renal function. Clin. J. Am. Soc. Nephrol., 2017, 5, 751-759.
[23]
Sonesson, C.; Johansson, P.A.; Johnsson, E.; Gause-Nilsson, I. Cardiovascular effects of dapagliflozin in patients with type 2 diabetes and different risk categories: A meta-analysis. Cardiovasc. Diabetol., 2016, 15, 37.
[24]
American Diabetes Association. standarts of medical care in diabetes. Comprehensive medical evaluation and assessment of comorbidities. Diabetes Care, 2017, 40(Suppl. 1), S25-S32.
[25]
Yamaguchi, M.; Shimizu, M.; Ino, H.; Terai, H.; Uchiyama, K.; Oe, K.; Mabuchi, T.; Konno, T.; Kaneda, T.; Mabuchi, H. T wave peak-to-end interval and qt dispersion in acquired long qt syndrome: A new index for arrhythmogenicity. Clin. Sci. (Lond.), 2003, 6, 671-676.
[26]
Ciobanu, A.; Tse, G.; Liu, T.; Deaconu, M.V.; Gheorghe, G.S.; Ilieşiu, A.M.; Nanea, I.T. Electrocardiographic measures of repolarization dispersion and their relationships with echocardiographic indices of ventricular remodeling and premature ventricular beats in hypertension. J. Geriatr. Cardiol., 2017, 12, 717-724.
[27]
Tse, G.; Gong, M.; Wong, W.T.; Georgopoulos, S.; Letsas, K.P.; Vassiliou, V.S.; Chan, Y.S.; Yan, B.P.; Wong, S.H.; Wu, W.K.K.; Ciobanu, A.; Li, G.; Shenthar, J.; Saguner, A.M.; Ali-Hasan-Al-Saegh, S.; Bhardwaj, A.; Sawant, A.C.; Whittaker, P.; Xia, Y.; Yan, G.X.; Liu, T. The tpeak - tend interval as an electrocardiographic risk marker of arrhythmic and mortality outcomes: A systematic review and meta-analysis. Heart Rhythm, 2017, 8, 1131-1137.
[28]
Raz, I.; Mosenzon, O.; Bonaca, M.P.; Cahn, A.; Kato, E.T.; Silverman, M.G.; Bhatt, D.L.; Leiter, L.A.; McGuire, D.K.; Wilding, J.P.H.; Gause-Nilsson, I.A.M.; Langkilde, A.M.; Johansson, P.A.; Sabatine, M.S.; Wiviott, S.D. Declare-timi 58: Participants’ baseline characteristics. Diabetes Obes. Metab., 2018, 20, 1102-1110.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy