Empaglifozin and the Reduction of Risk of Death in a High Cardiovascular Risk Population
Keywords:Diabetes Mellitus, Empagliflozin, Cardiovascular Disease,
AbstractDiabetes Mellitus (DM) is a chronic cardio-metabolic disease and plays an important role on cardiovascular outcomes, most importantly when associated with an already established heart disease. Its effects in the body involve both metabolic and structural changes. To avoid such complications, in addition to the strategies already used and known, rises the Empaglifozin, a sodium glucose co-transporter inhibitor 2 (SGLT2). Its benefits and efficacy have been tried and tested in large-scale trials, with multidimensional cardiovascular effects that go beyond the adequate glycemic control. The EMPA-REG Outcome materialize such benefits, especially for people at high cardiovascular risk, when significantly reduced cardiovascular death and death from any cause in this population.
Sarwar, N., Gao, P., Seshasai, S. (2010) Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102. Lancet 375, 2215-22.
Beckman, J., Creager, M., Libby, P. (2002) Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. JAMA 287, 2570-81.
Bernard, Z., Christoph, W., John, M. L., David, F., Erich, B., Stefan, H., Michaela, M., Theresa, D., Odd, E. J., Hans, J. W., Uli, C. B., Silvio, E. I. (november 2015) Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. The new england journal of medicine 373(22).
RA., D. (2009) Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 58, 773-95.
Brunton, S. A. (October 2015) The potential role of sodium glucose co-transporter 2 inhibitors in the early treatment of type 2 diabetes mellitus. The Interanational journal of clinical practice 69(10), 1071â€“1087.
Bellien, J., Favre, J., Iacob, M., Gao, J., Thuillez, C., Richard, V., Joannides, R. (2010) Arterial stiffness is regulated by nitric oxide and endothelium-derived hyperpolarizing factor during changes in blood flow in humans. Hypertension 55, 674â€“680.
Sasson, A., Cherney, D. (2012) Renal hyperfiltration related to diabetes mellitus and obesity in human disease. World J Diabetes 3, 1-6.
David, Z. C., Bruce, A. P., Nima, S., Ronnie, H., Nora, F., Odd, E. J., Hans-Juergen, W., Maximilian, v. E., Uli, C. B. (2014) The effect of empagliflozin on arterial stiffness and heart rate variability in subjects with uncomplicated type 1 diabetes mellitus. Cardiovascular Diabetology 13(28).
Oelze, M., Kroller-Schon, S., Welschof, P., Jansen, T., Hausding, M., Mikhed, Y., Stamm, P., Mader, M., ZinÃŸius, E., Agdauletova, S., Gottschlich, A., Stevens, S., Bottari, S., Mayoux, E., MÃ¼nzel, T., Daiber, A. (2014) The sodium-glucose co-transporter 2 inhibitor empagliflozin improves diabetes-induced vascular dysfunction in the streptozotocin diabetes rat model by interfering with oxidative stress and glucotoxicity. PLoS One 9(11), 17-11.
Martin, C. M., Eric, M., Volker, V. (June 2015) A comprehensive review of the pharmacodynamics of the SGLT2 inhibitor empagliflozin in animals and humans. Naunyn-Schmiedeberg's Arch Pharmacol 388, 801-816.
American Diabetes Association (2013) Standards of medical care in diabetes-2013. Diabetes Care 36.
Bernard, Z., Silvio, E. I., John, M. L., Christoph, W., Roberto, F., David, F., Erich, B., Stefan, H., Joan, KR., Jennifer, N., Odd, E. J., Hans-Juergen, W., Uli, C. B. (2014) Rationale, design, and baseline characteristics of a randomized, placebo-controlled cardiovascular outcome trial of empagliflozin (EMPA-REG OUTCOME)..
Grempler, R., Thomas, L., Eckhardt, M. (2012) Empagliflozin, a novel selective sodium glucose cotransporter-2 (SGLT-2) inhibitor: characterisation and comparison with other SGLT-2 inhibitors. Diabetes Obes Metab 14, 83-90.
Liakos,., Karagiannis,., Athanasiadou,., Sarigianni, M., Mainou,., Papatheodorou,., Bekiari ,., Tsapas,. (2014) Efficacy and safety of empagliflozin for type 2 diabetes: a systematic review and meta-analysis. Diabetes, Obesity and Metabolism 16, 984â€“993.
DeFronzo, R., Davidson, J., del Prado, S. (2012) The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia. Diabetes Obes Metab 14, 5-14.
Feldstein, A., Nichols, G., Smith, D. (2008) Weight change in diabetes and glycemic and blood pressure control. Diabetes Care 31, 1960-1965.
List, J., Whaley, J. (2011) Glucose dynamics and mechanistic implications of SGLT2 inhibitors in animals and humans. Kidney Int Suppl 120.
Araki, E., Tanizawa, Y., Tanaka, Y., Taniguchi, A., Koiwai , K., Kim, G., Salsali, A., J. Woerle, H., C. Broedl, U. (2015) Long-term treatment with empagliflozin as add-on to oral antidiabetes therapy in Japanese patients with type 2 diabetes mellitus. Diabetes, Obesity and Metabolism 17, 665-674.
Haring, HU., Merker, L., Seewaldt-Becker, E., Weimer, M., Meinicke, T., Woerle, H., Broedl, U. (2013) Empagliflozin as add-on to metformin plus sulfonylurea in patients with type 2 diabetes: a 24-week randomized, double-blind, placebo-controlled trial. Diabetes Care 36, 3396â€“3404.
Barnett, A., Mithal, A., Manassie, J., Jones, R., Rattunde, H., Woerle, H., Broedl, U. (2014) Efficacy and safety of empagliflozin added to existing anti-diabetes therapy in patients with type 2 diabetes and chronic kidney disease: a randomised, double-blind, placebocontrolled trial. Lancet Diabetes Endocrinol 2, 369-384.
Chilton, R., Tikkanen, I., P. Cannon, C., Crowe, S., J. Woerle, H., C. Broedl, U., E. Johansen, O. (2015) Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes. Diabetes, Obesity and Metabolism 17, 1180-1193.
Moss, S., Klein, R., Klein, B., Meuer, S. (1994) The association of glycemia and cause-specific mortality in a diabetic population. Arch Intern Med 154(21), 2473-9.
Kosuge, M., Kimura, K., Kojima, S., Sakamoto, T., Matsui, K., Ishihara, M. (2005) Japanese Acute Coronary Syndrome Study (JACSS) Investigators. Effects of glucose abnormalities on in-hospital outcome after coronary intervention for acute myocardial infarction. Circ J. 69(4), 375-9.
Marcelo, B., AndrÃ© de Castro, L., Deize, C., Paulo Roberto, F. R., Mirnaluci Paulino, R. G. (2013) Is glycated hemoglobin a predictor for the anatomical severity and extent of coronary artery disease? Rev Bras Cardiol. 26(2), 120-126.
kadowaki, T., Haneda, M., Inagaki, N., Terauchi, Y., Taniguchi, A., Koiwai, K. (2014) Empagliflozin monotherapy in Japanese patients with type 2 diabetes mellitus: a randomized, 12-week, double-blind, placebo-controlled, phase II trial. Adv Ther. 31(6), 621-38.
Woerle, H., Kadowaki, T., Haneda, M., Inagaki, A., Sakamoto, M., Koiwai, K. (2013) Safety and efficacy of empagliflozin monotherapy in a 52-week study in Japanese patients with type 2 diabetes mellitus. Diabetologia 56.
Rimei, N., Yoko, T., Kazuki, K., Kohei, I., Thomas, H., Afshin, S., Soren, S. L., Uli, C. B. (2015) Effect of empagliflozin monotherapy on postprandial glucose and 24-hour glucose variability in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled, 4-week study. Nishimura et al. Cardiovascular Diabetology 14(11).
Ilkka, T., Kirsi, N., Cordula, Z., Alexandra, G., Uli, C. B., Hans, J. W. (2015) Empagliflozin Reduces Blood Pressure in Patients With Type 2 Diabetes and Hypertension. Diabetes Care 38, 420-428.
Inzucchi, S., Zinman, B., Wanner, C. (2015) SGLT-2 inhibitors and cardiovascular risk: proposed pathways and review of ongoing outcome trials. Diab Vasc Dis Res 12, 90-100.
Cherney, D., Perkins, B., Soleymanlou, N. (2014) The effect of empagliflozin on arterial stiffness and heart rate variability in subjects with uncomplicated type 1 diabetes mellitus. Cardiovasc Diabetol 13(28).
Cardoso, C., Ferreira, M., Leite, N., Salles, G. (2013) Prognostic impact of aortic stiffness in high-risk type 2 diabetic patients: the Rio de Janeiro Type 2 Diabetes Cohort Study. Diabetes Care 36, 2772-8.
Chilton, R., Tikkanen, I., Cannon, C. (september 2014) Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes. Diabetes Obes Metab.
Ronco, C., McCullough, P., Anker, S. (2010) Cardio-renal syndromes: report from the consensus conference of the Acute Dialysis Quality Iniciative. Eur Heart J 31, 703-11.
Cherney, D., Perkins, B., Soleymanlou, N. (2014) Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation 129, 587-97.
Bakris, G., Molitch, M. (2014) Microalbuminuria as a risk predictor in diabetes: the continuing saga. Diabetes Care 37, 867-75.
Roden, M., Weng, J., Eilbracht, J. (2013) Empagliflozin monotherapy in drug-naive patients with type 2 diabetes: a randomised, 24-week, double-blind, placebo-controlled, parallel group, trial with sitagliptin as active comparator. Lancet Diabetes Endocrinol 1, 208-219.
Haring, H., Merker, L., Seewaldt-Bercker, E. (2014) Empagliflozin as add-on to metformin in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care 37, 1650-1659.
Kovacs, C., Seshiah, V., Swallow, R. (2014) Empagliflozin improves glycaemic and weight control as add-on therapy to pioglitazone or pioglitazone plus metformin in patients with type 2 diabetes: a 24-week, randomized, placebo-controlled trial. Diabetes Obes Metab 16, 147-158.
Ridderstrale, M., Anderson, K., Zeller, C. (2014) Comparison of empagliflozin and glimepiride as add-on to metformin in patients with type 2 diabetes: a 104-week randomised, active-controlled, double-blind, phase 3 trial. Lancet Diabetes Endocrinol 2, 691-700.
Vasilakou, D., Karagiannis, T., Athanasiadou, E. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. 2013 159, 262-274.
Monami, M., Nardini, C., Mannucci, E. (2014) Efficacy and safety of sodium glucose co-transport-2 inhibitors in type 2 diabetes: a meta-analysis of randomized clinical trials. Diabetes Obes Metab 16, 457â€“466..
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