Cardiorenal Impact of SGLT-2 Inhibitors: A Conceptual Revolution in The Management of Type 2 Diabetes, Heart Failure and Chronic Kidney Disease.

Type 2 Diabetes Mellitus (T2DM) is associated with an elevated incidence of cardiovascular and renal diseases, responsible for mortality rates significantly higher than in the general population. The management of both cardiovascular risk and progression of kidney disease thus seem crucial in the treatment of the diabetic patient. The availability of new classes of drugs which positively affect both cardiovascular and renal risk, regardless of the glycemic control, represents a revolution in the treatment of T2DM and shifts the attention from the intensive glycemic control to a holistic management of the diabetic patient. Among these, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been associated with a remarkable reduction of cardiovascular and renal mortality, lower hospitalization rates for heart failure and lower progression of renal damage and albuminuria. Thus, their use in selected subpopulations seems mandatory. Aim of this review was the assessment of the current evidence on SGLT2i and their related impact on the cardiovascular and renal profiles.

[1]  J. McMurray,et al.  Effect of dapagliflozin on urinary albumin excretion in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial. , 2021, The lancet. Diabetes & endocrinology.

[2]  D. Atar,et al.  Influence of receptor selectivity on benefits from SGLT2 inhibitors in patients with heart failure: a systematic review and head-to-head comparative efficacy network meta-analysis , 2021, Clinical Research in Cardiology.

[3]  V. Fuster,et al.  Mechanistic Insights of Empagliflozin in Nondiabetic Patients With HFrEF: From the EMPA-TROPISM Study. , 2021, JACC. Heart failure.

[4]  A. Kjær,et al.  Effects of Empagliflozin on Myocardial Flow Reserve in Patients With Type 2 Diabetes Mellitus: The SIMPLE Trial , 2021, Journal of the American Heart Association.

[5]  R. Torella,et al.  Efficacy and durability of multifactorial intervention on mortality and MACEs: a randomized clinical trial in type-2 diabetic kidney disease , 2021, Cardiovascular Diabetology.

[6]  L. Lund,et al.  Cardiac, renal, and metabolic effects of sodium–glucose co‐transporter 2 inhibitors: a position paper from the European Society of Cardiology ad‐hoc task force on sodium–glucose co‐transporter 2 inhibitors , 2021, European journal of heart failure.

[7]  D. Matthews,et al.  Comparative efficacy of glucose‐lowering medications on body weight and blood pressure in patients with type 2 diabetes: A systematic review and network meta‐analysis , 2021, Diabetes, obesity & metabolism.

[8]  A. Villaflor,et al.  Effects of dapagliflozin on mortality in patients with chronic kidney disease: a pre-specified analysis from the DAPA-CKD randomized controlled trial , 2021, European heart journal.

[9]  A. Sposito,et al.  Dapagliflozin effect on endothelial dysfunction in diabetic patients with atherosclerotic disease: a randomized active-controlled trial , 2021, Cardiovascular Diabetology.

[10]  G. Filippatos,et al.  Empagliflozin in Patients With Heart Failure, Reduced Ejection Fraction, and Volume Overload: EMPEROR-Reduced Trial. , 2021, Journal of the American College of Cardiology.

[11]  N. Hawkins,et al.  Pharmacotherapy for heart failure with reduced ejection fraction and health‐related quality of life: a systematic review and meta‐analysis , 2021, European journal of heart failure.

[12]  P. Ponikowski,et al.  Sodium–glucose co‐transporter 2 inhibition in patients hospitalized for acute decompensated heart failure: rationale for and design of the EMPULSE trial , 2021, European journal of heart failure.

[13]  M. Roncaglioni,et al.  Lower risk of death and cardiovascular events in patients with diabetes initiating glucagon‐like peptide‐1 receptor agonists or sodium‐glucose cotransporter‐2 inhibitors: A real‐world study in two Italian cohorts , 2021, Diabetes, obesity & metabolism.

[14]  Ze-Lin Zhan,et al.  Meta‐analysis of the effects of four factors on the efficacy of SGLT2 inhibitors in patients with HFrEF , 2021, ESC heart failure.

[15]  Y. Aso,et al.  Empagliflozin increases plasma levels of campesterol, a marker of cholesterol absorption, in patients with type 2 diabetes: Association with a slight increase in high-density lipoprotein cholesterol. , 2021, International journal of cardiology.

[16]  B. Pitt,et al.  Dapagliflozin effects on lung fluid volumes in patients with heart failure and reduced ejection fraction: Results from the DEFINE‐HF trial , 2021, Diabetes, obesity & metabolism.

[17]  David W. Johnson,et al.  Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials , 2021, BMJ.

[18]  Lawrence A Leiter,et al.  Empagliflozin Reduces Myocardial Extracellular Volume in Patients With Type 2 Diabetes and Coronary Artery Disease. , 2021, JACC. Cardiovascular imaging.

[19]  Deepak L. Bhatt,et al.  The cost‐effectiveness of dapagliflozin in treating high‐risk patients with type 2 diabetes mellitus: An economic evaluation using data from the DECLARE‐TIMI 58 trial , 2020, Diabetes, obesity & metabolism.

[20]  L. Køber,et al.  Effects of empagliflozin on estimated extracellular volume, estimated plasma volume, and measured glomerular filtration rate in patients with heart failure (Empire HF Renal): a prespecified substudy of a double-blind, randomised, placebo-controlled trial. , 2020, The lancet. Diabetes & endocrinology.

[21]  H. Heerspink,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 , 2020, Diabetes Care.

[22]  B. Zinman,et al.  Insights from CREDENCE trial indicate an acute drop in estimated glomerular filtration rate during treatment with canagliflozin with implications for clinical practice. , 2020, Kidney international.

[23]  D. J. Veldhuisen,et al.  Effects of empagliflozin on renal sodium and glucose handling in patients with acute heart failure , 2020, European journal of heart failure.

[24]  Deepak L. Bhatt,et al.  Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure. , 2020, The New England journal of medicine.

[25]  Deepak L. Bhatt,et al.  Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease. , 2020, The New England journal of medicine.

[26]  A. Tsapas,et al.  Dapagliflozin decreases ambulatory central blood pressure and pulse wave velocity in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial. , 2020, Journal of hypertension.

[27]  V. Fuster,et al.  Randomized Trial of Empagliflozin in Non-Diabetic Patients with Heart Failure and Reduced Ejection Fraction. , 2020, Journal of the American College of Cardiology.

[28]  A. Levin,et al.  Early Change in Albuminuria with Canagliflozin Predicts Kidney and Cardiovascular Outcomes: A Post Hoc Analysis from the CREDENCE Trial. , 2020, Journal of the American Society of Nephrology : JASN.

[29]  C. Cannon,et al.  Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes. , 2020, The New England journal of medicine.

[30]  Addendum. 10. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes—2020. Diabetes Care 2020;43(Suppl. 1):S111–S134 , 2020, Diabetes Care.

[31]  Deepak L. Bhatt,et al.  Effect of Empagliflozin on Left Ventricular Mass in Patients with Type 2 Diabetes and Coronary Artery Disease: The EMPA-HEART CardioLink-6 Randomized Clinical Trial. , 2019, Circulation.

[32]  Deepak L. Bhatt,et al.  SGLT2 Inhibition with Empagliflozin Increases Circulating Provascular Progenitor Cells in People with Type 2 Diabetes Mellitus. , 2019, Cell metabolism.

[33]  R. Marfella,et al.  Relationship between albuminuric CKD and diabetic retinopathy in a real-world setting of type 2 diabetes: Findings from No blind study. , 2019, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[34]  S. Verma,et al.  Direct Effects of Empagliflozin on Extracellular Matrix Remodelling in Human Cardiac Myofibroblasts: Novel Translational Clues to Explain EMPA-REG OUTCOME Results. , 2019, The Canadian journal of cardiology.

[35]  M. Drazner,et al.  Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients With Heart Failure With Reduced Ejection Fraction: The DEFINE-HF Trial. , 2019, Circulation.

[36]  M. Jardine,et al.  Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes mellitus and chronic kidney disease: A systematic review and meta‐analysis , 2019, Diabetes, obesity & metabolism.

[37]  J. Izzo,et al.  Antihyperglycemic and Blood Pressure Effects of Empagliflozin in Black Patients With Type 2 Diabetes Mellitus and Hypertension , 2019, Circulation.

[38]  Fen Li,et al.  Dapagliflozin Attenuates Cardiac Remodeling in Mice Model of Cardiac Pressure Overload , 2019, American journal of hypertension.

[39]  B. Zinman,et al.  Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. , 2019, The New England journal of medicine.

[40]  Po-Len Liu,et al.  The sodium–glucose co-transporter 2 inhibitor empagliflozin attenuates cardiac fibrosis and improves ventricular hemodynamics in hypertensive heart failure rats , 2019, Cardiovascular Diabetology.

[41]  H. Bøtker,et al.  Cardiovascular Effects of Treatment With the Ketone Body 3-Hydroxybutyrate in Chronic Heart Failure Patients , 2019, Circulation.

[42]  R. Agarwal,et al.  Ambulatory Blood Pressure Reduction With SGLT-2 Inhibitors: Dose-Response Meta-analysis and Comparative Evaluation With Low-Dose Hydrochlorothiazide , 2019, Diabetes Care.

[43]  A. Pontecorvi,et al.  Sotagliflozin, the first dual SGLT inhibitor: current outlook and perspectives , 2019, Cardiovascular Diabetology.

[44]  K. Connelly,et al.  Empagliflozin Improves Diastolic Function in a Nondiabetic Rodent Model of Heart Failure With Preserved Ejection Fraction , 2019, JACC. Basic to translational science.

[45]  D. Yellon,et al.  SGLT2 Inhibitor, Canagliflozin, Attenuates Myocardial Infarction in the Diabetic and Nondiabetic Heart , 2019, JACC. Basic to translational science.

[46]  Deepak L. Bhatt,et al.  Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes , 2019, The New England journal of medicine.

[47]  Marc P. Bonaca,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 , 2019, The Lancet.

[48]  K. Kario,et al.  24-Hour Blood Pressure-Lowering Effect of an SGLT-2 Inhibitor in Patients with Diabetes and Uncontrolled Nocturnal Hypertension: Results from the Randomized, Placebo-Controlled SACRA Study. , 2018, Circulation.

[49]  M. Elisaf,et al.  SGLT-2 inhibitors: pharmacokinetics characteristics and effects on lipids , 2018, Expert opinion on drug metabolism & toxicology.

[50]  E. Braunwald,et al.  Cardiac and Renal Effects of Sodium-Glucose Co-Transporter 2 Inhibitors in Diabetes: JACC State-of-the-Art Review. , 2018, Journal of the American College of Cardiology.

[51]  K. Mahaffey,et al.  Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials. , 2018, The lancet. Diabetes & endocrinology.

[52]  S. Verma,et al.  Empagliflozin Increases Cardiac Energy Production in Diabetes , 2018, JACC. Basic to translational science.

[53]  L. Maier,et al.  Empagliflozin reduces Ca/calmodulin‐dependent kinase II activity in isolated ventricular cardiomyocytes , 2018, ESC heart failure.

[54]  Lawrence A Leiter,et al.  Effects of canagliflozin versus glimepiride on adipokines and inflammatory biomarkers in type 2 diabetes. , 2018, Metabolism: clinical and experimental.

[55]  R. IJzerman,et al.  SGLT2 Inhibitors in Combination Therapy: From Mechanisms to Clinical Considerations in Type 2 Diabetes Management , 2018, Diabetes Care.

[56]  J. Shaw,et al.  Cardiovascular Events Associated With SGLT-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL 2 Study. , 2018, Journal of the American College of Cardiology.

[57]  M. Packer.  Do sodium‐glucose co‐transporter‐2 inhibitors prevent heart failure with a preserved ejection fraction by counterbalancing the effects of leptin? A novel hypothesis , 2018, Diabetes, obesity & metabolism.

[58]  W. Aronow.  Faculty of 1000 evaluation for Canagliflozin for primary and secondary prevention of cardiovascular events: results from the CANVAS program (canagliflozin cardiovascular assessment study). , 2018 .

[59]  A. Layton,et al.  SGLT2 inhibition in a kidney with reduced nephron number: modeling and analysis of solute transport and metabolism. , 2018, American journal of physiology. Renal physiology.

[60]  K. Kajiwara,et al.  The SGLT2 Inhibitor Dapagliflozin Significantly Improves the Peripheral Microvascular Endothelial Function in Patients with Uncontrolled Type 2 Diabetes Mellitus , 2018, Internal medicine.

[61]  J. McMurray,et al.  Why do SGLT2 inhibitors reduce heart failure hospitalization? A differential volume regulation hypothesis , 2018, Diabetes, obesity & metabolism.

[62]  R. Nelson,et al.  The Global Epidemiology of Diabetes and Kidney Disease. , 2018, Advances in chronic kidney disease.

[63]  Dongli Tian,et al.  Effects of sodium‐glucose co‐transporter 2 (SGLT2) inhibitors on serum uric acid level: A meta‐analysis of randomized controlled trials , 2018, Diabetes, obesity & metabolism.

[64]  R. Guthrie.  Canagliflozin and cardiovascular and renal events in type 2 diabetes , 2018, Postgraduate medicine.

[65]  M. Uder,et al.  SGLT-2-inhibition with dapagliflozin reduces tissue sodium content: a randomised controlled trial , 2018, Cardiovascular Diabetology.

[66]  Y. Aizawa,et al.  The effect of dapagliflozin treatment on epicardial adipose tissue volume , 2018, Cardiovascular Diabetology.

[67]  Biao Xu,et al.  Cardiovascular Safety, Long‐Term Noncardiovascular Safety, and Efficacy of Sodium–Glucose Cotransporter 2 Inhibitors in Patients With Type 2 Diabetes Mellitus: A Systemic Review and Meta‐Analysis With Trial Sequential Analysis , 2018, Journal of the American Heart Association.

[68]  R. Coronel,et al.  Class effects of SGLT2 inhibitors in mouse cardiomyocytes and hearts: inhibition of Na+/H+ exchanger, lowering of cytosolic Na+ and vasodilation , 2017, Diabetologia.

[69]  B. Zinman,et al.  How Does Empagliflozin Reduce Cardiovascular Mortality? Insights From a Mediation Analysis of the EMPA-REG OUTCOME Trial , 2017, Diabetes Care.

[70]  K. Mahaffey,et al.  Clinical Perspective What Is New ? , 2017 .

[71]  J. Udell,et al.  Sodium Glucose Cotransporter-2 Inhibition in Heart Failure: Potential Mechanisms, Clinical Applications, and Summary of Clinical Trials , 2017, Circulation.

[72]  L. Ghiadoni,et al.  Dapagliflozin acutely improves endothelial dysfunction, reduces aortic stiffness and renal resistive index in type 2 diabetic patients: a pilot study , 2017, Cardiovascular Diabetology.

[73]  R. Schmieder,et al.  Effects of the Selective Sodium-Glucose Cotransporter 2 Inhibitor Empagliflozin on Vascular Function and Central Hemodynamics in Patients With Type 2 Diabetes Mellitus. , 2017, Circulation.

[74]  J. Adamski,et al.  Effect of Empagliflozin on the Metabolic Signature of Patients With Type 2 Diabetes Mellitus and Cardiovascular Disease. , 2017, Circulation.

[75]  B. Carstensen,et al.  Cardiovascular mortality and morbidity in patients with type 2 diabetes following initiation of sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL Nordic): a multinational observational analysis. , 2017, The Lancet Diabetes and Endocrinology.

[76]  G. Filippatos,et al.  Effects of Sodium-Glucose Cotransporter 2 Inhibitors for the Treatment of Patients With Heart Failure: Proposal of a Novel Mechanism of Action , 2017, JAMA cardiology.

[77]  J. McMurray,et al.  The Metabolodiuretic Promise of Sodium-Dependent Glucose Cotransporter 2 Inhibition: The Search for the Sweet Spot in Heart Failure. , 2017, JAMA cardiology.

[78]  B. Zinman,et al.  Effects of empagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and established cardiovascular disease: an exploratory analysis from the EMPA-REG OUTCOME randomised, placebo-controlled trial. , 2017, The lancet. Diabetes & endocrinology.

[79]  S. Plein,et al.  Diabetes Mellitus, Microalbuminuria, and Subclinical Cardiac Disease: Identification and Monitoring of Individuals at Risk of Heart Failure , 2017, Journal of the American Heart Association.

[80]  M. Uder,et al.  Skin Sodium Concentration Correlates with Left Ventricular Hypertrophy in CKD. , 2017, Journal of the American Society of Nephrology : JASN.

[81]  K. Khunti,et al.  Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Glucose-Lowering Drugs , 2017, Circulation.

[82]  Björn Eliasson,et al.  Mortality and Cardiovascular Disease in Type 1 and Type 2 Diabetes , 2017, The New England journal of medicine.

[83]  R. Schmieder,et al.  A randomised study of the impact of the SGLT2 inhibitor dapagliflozin on microvascular and macrovascular circulation , 2017, Cardiovascular Diabetology.

[84]  V. Vallon,et al.  Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition , 2017, Diabetologia.

[85]  T. Hirano,et al.  Dapagliflozin decreases small dense low-density lipoprotein-cholesterol and increases high-density lipoprotein 2-cholesterol in patients with type 2 diabetes: comparison with sitagliptin , 2017, Cardiovascular Diabetology.

[86]  N. Inagaki,et al.  Factors Affecting Canagliflozin-Induced Transient Urine Volume Increase in Patients with Type 2 Diabetes Mellitus , 2016, Advances in Therapy.

[87]  R. Coronel,et al.  Empagliflozin decreases myocardial cytoplasmic Na+ through inhibition of the cardiac Na+/H+ exchanger in rats and rabbits , 2016, Diabetologia.

[88]  M. Al-Omran,et al.  Effect of Empagliflozin on Left Ventricular Mass and Diastolic Function in Individuals With Diabetes: An Important Clue to the EMPA-REG OUTCOME Trial? , 2016, Diabetes Care.

[89]  G. Kimura.  Diuretic Action of Sodium-Glucose Cotransporter 2 Inhibitors and Its Importance in the Management of Heart Failure. , 2016, Circulation journal : official journal of the Japanese Circulation Society.

[90]  S. Verma,et al.  Empagliflozin's Fuel Hypothesis: Not so Soon. , 2016, Cell metabolism.

[91]  C. Lang,et al.  Research into the effect Of SGLT2 inhibition on left ventricular remodelling in patients with heart failure and diabetes mellitus (REFORM) trial rationale and design , 2016, Cardiovascular Diabetology.

[92]  John M Lachin,et al.  Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. , 2016, The New England journal of medicine.

[93]  M. Fischereder,et al.  Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. , 2016, The New England journal of medicine.

[94]  E. Kılıç,et al.  Pleiotropic and Renoprotective Effects of Erythropoietin Beta on Experimental Diabetic Nephropathy Model , 2016, Nephron.

[95]  K. Margulies,et al.  Intracellular Na+ Concentration ([Na+]i) Is Elevated in Diabetic Hearts Due to Enhanced Na+–Glucose Cotransport , 2015, Journal of the American Heart Association.

[96]  C. White,et al.  Comparative Efficacy and Safety of Antidiabetic Drug Regimens Added to Metformin Monotherapy in Patients with Type 2 Diabetes: A Network Meta-Analysis , 2015, PloS one.

[97]  B. Perkins,et al.  Developmental Origins of Health and Disease Glycosuria-mediated urinary uric acid excretion in patients with uncomplicated type 1 diabetes mellitus , 2014 .

[98]  M. Woodward,et al.  Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. , 2014, The New England journal of medicine.

[99]  U. Broedl,et al.  Renal Hemodynamic Effect of Sodium-Glucose Cotransporter 2 Inhibition in Patients With Type 1 Diabetes Mellitus , 2014, Circulation.

[100]  T. Heise,et al.  Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. , 2014, The Journal of clinical investigation.

[101]  D. Kohan,et al.  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 , 2013, Kidney international.

[102]  M. Karmazyn.  NHE-1: still a viable therapeutic target. , 2013, Journal of molecular and cellular cardiology.

[103]  D. de Zeeuw,et al.  Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes , 2013, Diabetes, obesity & metabolism.

[104]  C. Pollock,et al.  Effects of SGLT2 Inhibition in Human Kidney Proximal Tubular Cells—Renoprotection in Diabetic Nephropathy? , 2013, PloS one.

[105]  B. Kestenbaum,et al.  Kidney disease and increased mortality risk in type 2 diabetes. , 2013, Journal of the American Society of Nephrology : JASN.

[106]  F. Mseeh,et al.  Improved glycemic control in mice lacking Sglt1 and Sglt2. , 2013, American journal of physiology. Endocrinology and metabolism.

[107]  M. Pelleymounter,et al.  Weight Loss Induced by Chronic Dapagliflozin Treatment Is Attenuated by Compensatory Hyperphagia in Diet‐Induced Obese (DIO) Rats , 2012, Obesity.

[108]  G. Remuzzi,et al.  Glomerular Hyperfiltration and Renal Disease Progression in Type 2 Diabetes , 2012, Diabetes Care.

[109]  R. Torella,et al.  High cardiovascular risk in patients with Type 2 diabetic nephropathy: the predictive role of albuminuria and glomerular filtration rate. The NID-2 Prospective Cohort Study. , 2012, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[110]  D. Maahs,et al.  Uric acid as a mediator of diabetic nephropathy. , 2011, Seminars in nephrology.

[111]  The Emerging Risk Factors Collaboration.  Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies , 2010, The Lancet.

[112]  B. O’Rourke,et al.  Elevated Cytosolic Na+ Increases Mitochondrial Formation of Reactive Oxygen Species in Failing Cardiac Myocytes , 2010, Circulation.

[113]  B. Pieske,et al.  Functional effects of glucose transporters in human ventricular myocardium , 2010, European journal of heart failure.

[114]  V. Salomaa,et al.  Risk factors for end‐stage renal disease in a community‐based population: 26‐year follow‐up of 25 821 men and women in eastern Finland , 2009, Journal of internal medicine.

[115]  C. Schneider,et al.  ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: application of natriuretic peptides. , 2008, European heart journal.

[116]  R. Torella,et al.  Management of cardiovascular risk factors in advanced type 2 diabetic nephropathy: a comparative analysis in nephrology, diabetology and primary care settings , 2006, Journal of hypertension.

[117]  S. Yusuf,et al.  Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. , 2001, JAMA.

[118]  R. Blantz,et al.  Glomerular hyperfiltration in experimental diabetes mellitus: potential role of tubular reabsorption. , 1999, Journal of the American Society of Nephrology : JASN.

[119]  V. Vallon,et al.  Acute and chronic effects of SGLT2 blockade on glomerular and tubular function in the early diabetic rat. , 2012, American journal of physiology. Regulatory, integrative and comparative physiology.

[120]  G. Moneta.  Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies , 2011 .

[121]  C. Folmes,et al.  Myocardial fatty acid metabolism in health and disease. , 2010, Physiological reviews.

[122]  S. Verma,et al.  Cardiac remodeling and failure From molecules to man (Part II). , 2005, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology.

[123]  A. G. Shaper,et al.  Obesity and cardiovascular disease. , 1996, Ciba Foundation symposium.