Heart failure in diabetes: Effects of anti-hyperglycaemic drug therapy

The Lancet

Volumn 385, Issue 9982, 2015, Pages 2107-2117

  Gilbert, Richard E ^a   Krum, Henry ^b  

^a ST MICHAEL'S HOSPITAL   (Canada)

^b MONASH UNIVERSITY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ALPHA GLUCOSIDASE INHIBITOR; ANTIDIABETIC AGENT; DIPEPTIDYL PEPTIDASE IV INHIBITOR; GLUCAGON LIKE PEPTIDE 1 RECEPTOR AGONIST; INSULIN; METFORMIN; PIOGLITAZONE; ROSIGLITAZONE; SAXAGLIPTIN; SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR; SULFONYLUREA; GLUCAGON LIKE PEPTIDE 1; GLYCOSIDASE INHIBITOR; SODIUM GLUCOSE COTRANSPORTER 2; SULFONYLUREA DERIVATIVE;

ANTIDIABETIC ACTIVITY; CARDIOVASCULAR RISK; DIABETES MELLITUS; GLYCEMIC CONTROL; HEART FAILURE; HIGH RISK POPULATION; HOSPITAL ADMISSION; HUMAN; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; ADULT; AGE DISTRIBUTION; AGED; ANTAGONISTS AND INHIBITORS; CHEMICALLY INDUCED; DIABETES MELLITUS, TYPE 2; DIABETIC CARDIOMYOPATHY; MIDDLE AGED; OBSERVATIONAL STUDY; RANDOMIZED CONTROLLED TRIAL (TOPIC); VERY ELDERLY;

ADULT; AGE DISTRIBUTION; AGED; AGED, 80 AND OVER; DIABETES MELLITUS, TYPE 2; DIABETIC CARDIOMYOPATHIES; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; GLUCAGON-LIKE PEPTIDE 1; GLYCOSIDE HYDROLASE INHIBITORS; HEART FAILURE; HUMANS; HYPOGLYCEMIC AGENTS; INSULIN; MIDDLE AGED; OBSERVATIONAL STUDY AS TOPIC; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SODIUM-GLUCOSE TRANSPORTER 2; SULFONYLUREA COMPOUNDS; THIAZOLIDINEDIONES;

EID: 84930079243     PISSN: 01406736     EISSN: 1474547X     Source Type: Journal    
DOI: 10.1016/S0140-6736(14)61402-1     Document Type: Review

References (107)

1. WB Kannel, M Hjortland, WP Castelli Role of diabetes in congestive heart failure: the Framingham study Am J Cardiol 34 1974 29 34
2. UK Prospective Diabetes Study (UKPDS) Group Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33) Lancet 352 1998 837 853
3. MR MacDonald, MC Petrie, F Varyani the CHARM Investigators Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme Eur Heart J 29 2008 1377 1385
4. GA Nichols, TA Hillier, JR Erbey, JB Brown Congestive heart failure in type 2 diabetes: prevalence, incidence, and risk factors Diabetes Care 24 2001 1614 1619
5. GA Nichols, CM Gullion, CE Koro, SA Ephross, JB Brown The incidence of congestive heart failure in type 2 diabetes: an update Diabetes Care 27 2004 1879 1884
6. DM Nathan, PA Cleary, JY Backlund the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes N Engl J Med 353 2005 2643 2653
7. A Patel, S MacMahon, J Chalmers the ADVANCE Collaborative Group Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes N Engl J Med 358 2008 2560 2572
8. EW Gregg, Y Li, J Wang et al. Changes in diabetes-related complications in the United States, 1990-2010 N Engl J Med 370 2014 1514 1523
9. DS Bell Heart failure: the frequent, forgotten, and often fatal complication of diabetes Diabetes Care 26 2003 2433 2441
10. H Krum, RE Gilbert Demographics and concomitant disorders in heart failure Lancet 362 2003 147 158
11. I Gustafsson, C Torp-Pedersen, L Køber, F Gustafsson, P Hildebrandt the Trace Study Group Effect of the angiotensin-converting enzyme inhibitor trandolapril on mortality and morbidity in diabetic patients with left ventricular dysfunction after acute myocardial infarction J Am Coll Cardiol 34 1999 83 89
12. CB Granger, JJ McMurray, S Yusuf the CHARM Investigators and Committees Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial Lancet 362 2003 772 776
13. SJ Haas, T Vos, RE Gilbert, H Krum Are beta-blockers as efficacious in patients with diabetes mellitus as in patients without diabetes mellitus who have chronic heart failure? A meta-analysis of large-scale clinical trials Am Heart J 146 2003 848 853
14. B Pitt, H White, J Nicolau the EPHESUS Investigators Eplerenone reduces mortality 30 days after randomization following acute myocardial infarction in patients with left ventricular systolic dysfunction and heart failure J Am Coll Cardiol 46 2005 425 431
15. C Fantoni, S Raffa, F Regoli et al. Cardiac resynchronization therapy improves heart rate profile and heart rate variability of patients with moderate to severe heart failure J Am Coll Cardiol 46 2005 1875 1882
16. SM Grundy, IJ Benjamin, GL Burke et al. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association Circulation 100 1999 1134 1146
17. A Abaci, A Oʇuzhan, S Kahraman et al. Effect of diabetes mellitus on formation of coronary collateral vessels Circulation 99 1999 2239 2242
18. E Chou, I Suzuma, KJ Way et al. Decreased cardiac expression of vascular endothelial growth factor and its receptors in insulin-resistant and diabetic States: a possible explanation for impaired collateral formation in cardiac tissue Circulation 105 2002 373 379
19. J Waltenberger Impaired collateral vessel development in diabetes: potential cellular mechanisms and therapeutic implications Cardiovasc Res 49 2001 554 560
20. PH Stone, JE Muller, T Hartwell the MILIS Study Group The effect of diabetes mellitus on prognosis and serial left ventricular function after acute myocardial infarction: contribution of both coronary disease and diastolic left ventricular dysfunction to the adverse prognosis J Am Coll Cardiol 14 1989 49 57
21. D Levy, MG Larson, RS Vasan, WB Kannel, KK Ho The progression from hypertension to congestive heart failure JAMA 275 1996 1557 1562
22. A Frustaci, J Kajstura, C Chimenti et al. Myocardial cell death in human diabetes Circ Res 87 2000 1123 1132
23. P Fioretto, B Muollo, PP Faronato et al. Relationships among natriuresis, atrial natriuretic peptide and insulin in insulin-dependent diabetes Kidney Int 41 1992 813 821
24. IM Stratton, AI Adler, HA Neil et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study BMJ 321 2000 405 412
25. FM Turnbull, C Abraira, RJ Anderson the Control Group Intensive glucose control and macrovascular outcomes in type 2 diabetes Diabetologia 52 2009 2288 2298
26. S Eshaghian, TB Horwich, GC Fonarow An unexpected inverse relationship between HbA1c levels and mortality in patients with diabetes and advanced systolic heart failure Am Heart J 151 2006 91
27. GS Tomova, V Nimbal, TB Horwich Relation between hemoglobin a(1c) and outcomes in heart failure patients with and without diabetes mellitus Am J Cardiol 109 2012 1767 1773
28. S Maru, GG Koch, M Stender et al. Antidiabetic drugs and heart failure risk in patients with type 2 diabetes in the U.K. primary care setting Diabetes Care 28 2005 20 26
29. The Kroc Collaborative Study Group Diabetic retinopathy after two years of intensified insulin treatment. Follow-up of the Kroc Collaborative Study JAMA 260 1988 37 41
30. The Diabetes Control and Complications Trial Research Group The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus N Engl J Med 329 1993 977 986
31. R Ruiter, LE Visser, MP van Herk-Sukel et al. Prescribing of rosiglitazone and pioglitazone following safety signals: analysis of trends in dispensing patterns in the Netherlands from 1998 to 2008 Drug Saf 35 2012 471 480
32. RW Nesto, D Bell, RO Bonow the American Heart Association the American Diabetes Association Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. October 7, 2003 Circulation 108 2003 2941 2948
33. European Medicines Agency Assessment Report for Avandia http://www.ema.europa.eu/docs/en-GB/document-library/EPAR---Assessment-Report---Variation/human/000268/WC500100757.pdf Dec 3, 2010 (accessed March 30, 2015).
34. TE Delea, JS Edelsberg, M Hagiwara, G Oster, LS Phillips Use of thiazolidinediones and risk of heart failure in people with type 2 diabetes: a retrospective cohort study Diabetes Care 26 2003 2983 2989
35. E Wooltorton Rosiglitazone (Avandia) and pioglitazone (Actos) and heart failure CMAJ 166 2002 219
36. A Benbow, M Stewart, G Yeoman Thiazolidinediones for type 2 diabetes. All glitazones may exacerbate heart failure BMJ 322 2001 236
37. SE Nissen The rise and fall of rosiglitazone Eur Heart J 31 2010 773 776
38. FA Masoudi, SE Inzucchi, Y Wang, EP Havranek, JM Foody, HM Krumholz Thiazolidinediones, metformin, and outcomes in older patients with diabetes and heart failure: an observational study Circulation 111 2005 583 590
39. Dream Trial Investigators GR Dagenais, HC GersteiN et al. Effects of ramipril and rosiglitazone on cardiovascular and renal outcomes in people with impaired glucose tolerance or impaired fasting glucose: results of the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial Diabetes Care 31 2008 1007 1014
40. JA Dormandy, B Charbonnel, DJ Eckland et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial Lancet 366 2005 1279 1289
41. GlaxoSmithKline Study 49653/211. A 52-week double-blind study of the effect of rosiglitazone on cardiovascular structure and function in subjects with type 2 diabetes mellitus and congestive heart failure (NYHA class I/II) http://www.gsk-clinicalstudyregister.com/study/49653/211#rs (accessed on May 1, 2015).
42. S Singh, YK Loke, CD Furberg Thiazolidinediones and heart failure: a teleo-analysis Diabetes Care 30 2007 2148 2153
43. SE Nissen, K Wolski Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes N Engl J Med 356 2007 2457 2471
44. Y Guan, C Hao, DR Cha et al. Thiazolidinediones expand body fluid volume through PPARgamma stimulation of ENaC-mediated renal salt absorption Nat Med 11 2005 861 866
45. G Seki, Y Endo, M Suzuki, H Yamada, S Horita, T Fujita Role of renal proximal tubule transport in thiazolidinedione-induced volume expansion World J Nephrol 1 2012 146 150
46. A Basu, MD Jensen, F McCann, D Mukhopadhyay, MJ Joyner, RA Rizza Effects of pioglitazone versus glipizide on body fat distribution, body water content, and hemodynamics in type 2 diabetes Diabetes Care 29 2006 510 514
47. J Karalliedde, RE Buckingham Thiazolidinediones and their fluid-related adverse effects: facts, fiction and putative management strategies Drug Saf 30 2007 741 753
48. M Emoto, N Fukuda, Y Nakamori et al. Plasma concentrations of vascular endothelial growth factor are associated with peripheral oedema in patients treated with thiazolidinedione Diabetologia 49 2006 2217 2218
49. RM Lago, PP Singh, RW Nesto Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials Lancet 370 2007 1129 1136
50. E Erdmann, B Charbonnel, RG Wilcox et al. Pioglitazone use and heart failure in patients with type 2 diabetes and preexisting cardiovascular disease: data from the PROactive study (PROactive 08) Diabetes Care 30 2007 2773 2778
51. M Komajda, JJ McMurray, H Beck-Nielsen et al. Heart failure events with rosiglitazone in type 2 diabetes: data from the RECORD clinical trial Eur Heart J 31 2010 824 831
52. YK Loke, CS Kwok, S Singh Comparative cardiovascular effects of thiazolidinediones: systematic review and meta-analysis of observational studies BMJ 342 2011 d1309
53. AM Lincoff, JC Tardif, GG Schwartz et al. Effect of aleglitazar on cardiovascular outcomes after acute coronary syndrome in patients with type 2 diabetes mellitus: the AleCardio randomized clinical trial JAMA 311 2014 1515 1525
54. BM Scirica, DL Bhatt, E Braunwald the SAVOR-TIMI 53 Steering Committee and Investigators Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus N Engl J Med 369 2013 1317 1326
55. BM Scirica, E Braunwald, I Raz et al. Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial Circulation 130 2014 1579 1588
56. WB White, CP Cannon, SR Heller the EXAMINE Investigators Alogliptin after acute coronary syndrome in patients with type 2 diabetes N Engl J Med 369 2013 1327 1335
57. F Zannad, CP Cannon, WC Cushman et al. Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial Lancet 2015 published online March 9. http://dx.doi.org/10.1016/S0140-6736(14)62225-X
58. J McMurray The Vildagliptin in Ventricular Dysfunction Diabetes trial (VIVIDD) European Heart Failure Congress 2013
59. S Wu, I Hopper, M Skiba, H Krum Dipeptidyl peptidase-4 inhibitors and cardiovascular outcomes: Meta-analysis of randomized clinical trials with 55,141 participants Cardiovasc Ther 32 2014 147 158
60. DL Weir, FA McAlister, A Senthilselvan, JK Minhas-Sandhu, DT Eurich Sitagliptin use in patients with diabetes and heart failure: a population-based retrospective cohort study JACC Heart Fail 2 2014 573 582
61. RP Hoffman Sympathetic mechanisms of hypoglycemic counterregulation Curr Diabetes Rev 3 2007 185 193
62. A Marney, S Kunchakarra, L Byrne, NJ Brown Interactive hemodynamic effects of dipeptidyl peptidase-IV inhibition and angiotensin-converting enzyme inhibition in humans Hypertension 56 2010 728 733
63. EK Jackson, Z Mi Sitagliptin augments sympathetic enhancement of the renovascular effects of angiotensin II in genetic hypertension Hypertension 51 2008 1637 1642
64. JB Green, MA Bethel, SK Paul et al. Rationale, design, and organization of a randomized, controlled Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) in patients with type 2 diabetes and established cardiovascular disease Am Heart J 166 2013 983 989
65. Merck Merck announces the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) met primary endpoint www.mercknewsroom.com/news-release/prescription-medicine-news/merck-announces-trial-evaluating-cardiovascular-outcomes-sit (accessed May 3, 2015).
66. I Thrainsdottir, K Malmberg, A Olsson, M Gutniak, L Rydén Initial experience with GLP-1 treatment on metabolic control and myocardial function in patients with type 2 diabetes mellitus and heart failure Diab Vasc Dis Res 1 2004 40 43
67. GG Sokos, LA Nikolaidis, S Mankad, D Elahi, RP Shannon Glucagon-like peptide-1 infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure J Card Fail 12 2006 694 699
68. M Halbirk, H Nørrelund, N Møller et al. Cardiovascular and metabolic effects of 48-h glucagon-like peptide-1 infusion in compensated chronic patients with heart failure Am J Physiol Heart Circ Physiol 298 2010 H1096 H1102
69. A Leifer A case of insilun edema JAMA 90 1928 610 611
70. GN Kalambokis, AA Tsatsoulis, EV Tsianos The edematogenic properties of insulin Am J Kidney Dis 44 2004 575 590
71. RA DeFronzo, CR Cooke, R Andres, GR Faloona, PJ Davis The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man J Clin Invest 55 1975 845 855
72. P Skøtt, O Hother-Nielsen, NE Bruun et al. Effects of insulin on kidney function and sodium excretion in healthy subjects Diabetologia 32 1989 694 699
73. AP Rocchini, V Katch, D Kveselis et al. Insulin and renal sodium retention in obese adolescents Hypertension 14 1989 367 374
74. A Natali, A Quiñones Galvan, D Santoro et al. Relationship between insulin release, antinatriuresis and hypokalaemia after glucose ingestion in normal and hypertensive man Clin Sci (Lond) 85 1993 327 335
75. E Muscelli, A Natali, S Bianchi et al. Effect of insulin on renal sodium and uric acid handling in essential hypertension Am J Hypertens 9 1996 746 752
76. R Nosadini, M Sambataro, K Thomaseth et al. Role of hyperglycemia and insulin resistance in determining sodium retention in non-insulin-dependent diabetes Kidney Int 44 1993 139 146
77. R Nakamura, DS Emmanouel, AI Katz Insulin binding sites in various segments of the rabbit nephron J Clin Invest 72 1983 388 392
78. DG Fuster, IA Bobulescu, J Zhang, J Wade, OW Moe Characterization of the regulation of renal Na+/H+ exchanger NHE3 by insulin Am J Physiol Renal Physiol 292 2007 F577 F585
79. E Féraille, ML Carranza, M Rousselot, H Favre Insulin enhances sodium sensitivity of Na-K-ATPase in isolated rat proximal convoluted tubule Am J Physiol 267 1994 F55 F62
80. OS Ruiz, YY Qiu, LR Cardoso, JA Arruda Regulation of the renal Na-HCO3 cotransporter: IX. Modulation by insulin, epidermal growth factor and carbachol Regul Pept 77 1998 155 161
81. N Takahashi, O Ito, K Abe Tubular effects of insulin Hypertens Res 19 suppl 1 1996 S41 S45
82. S Horita, G Seki, H Yamada, M Suzuki, K Koike, T Fujita Insulin resistance, obesity, hypertension, and renal sodium transport Int J Hypertens 2011 2011 391762
83. JK Bubien Epithelial Na+ channel (ENaC), hormones, and hypertension J Biol Chem 285 2010 23527 23531
84. P Raskin, M Rendell, MC Riddle, JF Dole, MI Freed, J Rosenstock the Rosiglitazone Clinical Trials Study Group A randomized trial of rosiglitazone therapy in patients with inadequately controlled insulin-treated type 2 diabetes Diabetes Care 24 2001 1226 1232
85. SJ Pocock, D Wang, MA Pfeffer et al. Predictors of mortality and morbidity in patients with chronic heart failure Eur Heart J 27 2006 65 75
86. M Mangiavacchi, M Gasparini, S Genovese et al. Insulin-treated type 2 diabetes is associated with a decreased survival in heart failure patients after cardiac resynchronization therapy Pacing Clin Electrophysiol 31 2008 1425 1432
87. AM Murcia, CH Hennekens, GA Lamas et al. Impact of diabetes on mortality in patients with myocardial infarction and left ventricular dysfunction Arch Intern Med 164 2004 2273 2279
88. S Smooke, TB Horwich, GC Fonarow Insulin-treated diabetes is associated with a marked increase in mortality in patients with advanced heart failure Am Heart J 149 2005 168 174
89. GA Nichols, CE Koro, CM Gullion, SA Ephross, JB Brown The incidence of congestive heart failure associated with antidiabetic therapies Diabetes Metab Res Rev 21 2005 51 57
90. AJ Karter, AT Ahmed, J Liu, HH Moffet, MM Parker Pioglitazone initiation and subsequent hospitalization for congestive heart failure Diabet Med 22 2005 986 993
91. UK Prospective Diabetes Study (UKPDS) Group Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33) Lancet 352 1998 837 853
92. UK Prospective Diabetes Study (UKPDS) Group Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34) Lancet 352 1998 854 865
93. RL Frye, P August, MM Brooks the BARI 2D Study Group A randomized trial of therapies for type 2 diabetes and coronary artery disease N Engl J Med 360 2009 2503 2515
94. FA McAlister, DT Eurich, SR Majumdar, JA Johnson The risk of heart failure in patients with type 2 diabetes treated with oral agent monotherapy Eur J Heart Fail 10 2008 703 708
95. KM Pantalone, MW Kattan, C Yu et al. The risk of developing coronary artery disease or congestive heart failure, and overall mortality, in type 2 diabetic patients receiving rosiglitazone, pioglitazone, metformin, or sulfonylureas: a retrospective analysis Acta Diabetol 46 2009 145 154
96. I Tzoulaki, M Molokhia, V Curcin et al. Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database BMJ 339 2009 b4731
97. DT Eurich, SR Majumdar, FA McAlister, RT Tsuyuki, JA Johnson Improved clinical outcomes associated with metformin in patients with diabetes and heart failure Diabetes Care 28 2005 2345 2351
98. SE Inzucchi, FA Masoudi, Y Wang et al. Insulin-sensitizing antihyperglycemic drugs and mortality after acute myocardial infarction: insights from the National Heart Care Project Diabetes Care 28 2005 1680 1689
99. G Giamouzis, F Triposkiadis, J Butler Metformin use in patients with diabetes mellitus and heart failure: friend or foe? J Card Fail 16 2010 207 210
100. DT Eurich, DL Weir, SR Majumdar et al. Comparative safety and effectiveness of metformin in patients with diabetes mellitus and heart failure: systematic review of observational studies involving 34,000 patients Circ Heart Fail 6 2013 395 402
101. W Yang, J Liu, Z Shan et al. Acarbose compared with metformin as initial therapy in patients with newly diagnosed type 2 diabetes: an open-label, non-inferiority randomised trial Lancet Diabetes Endocrinol 2 2014 46 55
102. Endocrinologic and Metabolic Drugs Advisory Committee Meeting Dapagliflozin BMS- 512148 http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Endocri nologicandMetabolicDrugsAdvisoryCommittee/UCM379659.pdf Dec 12, 2013 (accessed March 22, 2015).
103. SK Banerjee, KR McGaffin, NM Pastor-Soler, F Ahmad SGLT1 is a novel cardiac glucose transporter that is perturbed in disease states Cardiovasc Res 84 2009 111 118
104. L Zhou, EV Cryan, MR D'Andrea, S Belkowski, BR Conway, KT Demarest Human cardiomyocytes express high level of Na+/glucose cotransporter 1 (SGLT1) J Cell Biochem 90 2003 339 346
105. SK Banerjee, DW Wang, R Alzamora et al. SGLT1, a novel cardiac glucose transporter, mediates increased glucose uptake in PRKAG2 cardiomyopathy J Mol Cell Cardiol 49 2010 683 692
106. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM071627.pdf?utm-campaign=Google2utm-source=fdaSearchutm-medium=websiteutm-term=guidance (accessed March 22, 2015).
107. JJ McMurray, HC Gerstein, RR Holman, MA Pfeffer Heart failure: a cardiovascular outcome in diabetes that can no longer be ignored Lancet Diabetes Endocrinol 2 2014 843 851