SGLT2 inhibitors: hypotheses on the mechanism of cardiovascular protection

The Lancet Diabetes and Endocrinology

Volumn 6, Issue 6, 2018, Pages 435-437

  Bell, Robert M ^a   Yellon, Derek M ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

EMPAGLIFLOZIN; GLUCAGON; REACTIVE OXYGEN METABOLITE; SODIUM GLUCOSE COTRANSPORTER 1; SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR; SODIUM PROTON EXCHANGE PROTEIN; ANTIDIABETIC AGENT; BENZHYDRYL DERIVATIVE; CANAGLIFLOZIN; GLUCOSIDE;

CARDIOVASCULAR MORTALITY; CARDIOVASCULAR RISK; CELL PROTECTION; DRUG EFFECT; DRUG MECHANISM; GLUCAGON RELEASE; GLYCEMIC CONTROL; HEART FAILURE WITH PRESERVED EJECTION FRACTION; HEART FAILURE WITH REDUCED EJECTION FRACTION; HEART PROTECTION; HIGH RISK PATIENT; HUMAN; HYPOTHESIS; NONHUMAN; NOTE; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN EXPRESSION; SURVIVAL; CARDIOVASCULAR DISEASE; CLINICAL TRIAL (TOPIC); DIABETIC COMPLICATION; TREATMENT OUTCOME;

BENZHYDRYL COMPOUNDS; CANAGLIFLOZIN; CARDIOVASCULAR DISEASES; CLINICAL TRIALS AS TOPIC; DIABETES COMPLICATIONS; GLUCOSIDES; HUMANS; HYPOGLYCEMIC AGENTS; SODIUM-GLUCOSE TRANSPORTER 2 INHIBITORS; TREATMENT OUTCOME;

EID: 85030848386     PISSN: 22138587     EISSN: 22138595     Source Type: Journal    
DOI: 10.1016/S2213-8587(17)30314-5     Document Type: Note

References (15)

1. Heerspink, HJ, Perkins, BA, Fitchett, DH, Husain, M, Cherney, DZ, Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: cardiovascular and kidney effects, potential mechanisms, and clinical applications. Circulation 134 (2016), 752–772.
2. Zinman, B, Wanner, C, Lachin, JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 373 (2015), 2117–2128.
3. Neal, B, Perkovic, V, Mahaffey, KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 377 (2017), 644–657.
4. Kosiborod, M, Cavender, MA, Fu, AZ, et al. Lower risk of heart failure and death in patients initiated on sodium-glucose cotransporter-2 inhibitors versus other glucose-lowering drugs: the CVD-REAL study (comparative effectiveness of cardiovascular outcomes in new users of sodium-glucose cotransporter-2 inhibitors). Circulation 136 (2017), 249–259.
5. + exchanger in rats and rabbits. Diabetologia 60 (2017), 568–573.
6. + exchange inhibitors for cardioprotective therapy: progress, problems and prospects. J Am Coll Cardiol 39 (2002), 747–753.
7. Brown, DI, Griendling, KK, Regulation of signal transduction by reactive oxygen species in the cardiovascular system. Circ Res 116 (2015), 531–549.
8. Van Steenbergen, A, Balteau, M, Ginion, A, et al. Sodium-myoinositol cotransporter-1, SMIT1, mediates the production of reactive oxygen species induced by hyperglycemia in the heart. Sci Rep, 7, 2017, 41166.
9. Yamazaki, Y, Harada, S, Wada, T, Hagiwara, T, Yoshida, S, Tokuyama, S, Sodium influx through cerebral sodium-glucose transporter type 1 exacerbates the development of cerebral ischemic neuronal damage. Eur J Pharmacol 799 (2017), 103–110.
10. Al Jobori, H, Daniele, G, Adams, J, et al. Determinants of the increase in fasting plasma ketone concentration during SGLT2 inhibition in NGT, IFG and T2DM patients. Diabetes Obes Metab 19 (2017), 809–813.
11. Ceriello, A, Genovese, S, Mannucci, E, Gronda, E, Glucagon and heart in type 2 diabetes: new perspectives. Cardiovasc Diabetol, 15, 2016, 123.
12. 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 39 (2016), 1115–1122.
13. Ferrannini, E, Mark, M, Mayoux, E, CV protection in the EMPA-REG OUTCOME trial: a “thrifty substrate” hypothesis. Diabetes Care 39 (2016), 1108–1114.
14. Bertero, E, Roma, LP, Ameri, P, Maack, C, Cardiac effects of SGLT2 inhibitors: the sodium hypothesis. Cardiovasc Res, 2017 published online Aug 4. DOI:10.1093/cvr/cvx149.
15. Hammoudi, N, Jeong, D, Singh, R, et al. Empagliflozin improves left ventricular diastolic dysfunction in a genetic model of type 2 diabetes. Cardiovasc Drugs Ther, 2017 published online June 22. DOI:10.1007/s10557-017-6734-1.