EMPA-REG and Other Cardiovascular Outcome Trials of Glucose-lowering Agents: Implications for Future Treatment Strategies in Type 2 Diabetes Mellitus

Clinical Therapeutics

Volumn 38, Issue 6, 2016, Pages 1288-1298

  Schernthaner, Guntram ^a   Schernthaner Reiter, Marie Helene ^b   Schernthaner, Gerit Holger ^b  

^a KRANKENANSTALT RUDOLFSTIFTUNG   (Austria)

^b MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

cardiovascular disease; CV death; EMPA REG outcome study; heart failure; IRIS study; mortality

Indexed keywords

ALOGLIPTIN; ANTIDIABETIC AGENT; CANAGLIFLOZIN; EMPAGLIFLOZIN; INSULIN GLARGINE; LIRAGLUTIDE; LIXISENATIDE; METFORMIN; PIOGLITAZONE; SAXAGLIPTIN; SITAGLIPTIN; 2,4 THIAZOLIDINEDIONE DERIVATIVE; BENZHYDRYL DERIVATIVE; DIPEPTIDYL PEPTIDASE IV INHIBITOR; GLUCAGON LIKE PEPTIDE 1 RECEPTOR; GLUCOSIDE; SODIUM GLUCOSE COTRANSPORTER 2;

ACUTE CORONARY SYNDROME; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CEREBROVASCULAR ACCIDENT; CHRONIC KIDNEY DISEASE; DRUG EFFECT; GLOMERULUS FILTRATION RATE; GLYCEMIC CONTROL; HEART FAILURE; HEART INFARCTION; HUMAN; INCIDENCE; INSULIN DEPENDENT DIABETES MELLITUS; INSULIN RESISTANCE; META ANALYSIS; MODERATE RENAL IMPAIRMENT; NON INSULIN DEPENDENT DIABETES MELLITUS; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RISK REDUCTION; TREATMENT OUTCOME; ANTAGONISTS AND INHIBITORS; CARDIOVASCULAR DISEASES; CLINICAL TRIAL (TOPIC); COMBINATION DRUG THERAPY; COMPLICATION; DIABETES MELLITUS, TYPE 2; PROSPECTIVE STUDY;

BENZHYDRYL COMPOUNDS; CARDIOVASCULAR DISEASES; CLINICAL TRIALS AS TOPIC; DIABETES MELLITUS, TYPE 2; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; DRUG THERAPY, COMBINATION; GLUCAGON-LIKE PEPTIDE-1 RECEPTOR; GLUCOSIDES; HUMANS; HYPOGLYCEMIC AGENTS; METFORMIN; PROSPECTIVE STUDIES; SODIUM-GLUCOSE TRANSPORTER 2; THIAZOLIDINEDIONES;

EID: 84975292879     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/j.clinthera.2016.04.037     Document Type: Article

References (61)

1. 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
2. H.C. Gerstein, M.E. Miller, R.P. Byington, and et al. Effects of intensive glucose lowering in type 2 diabetes N Engl J Med 358 2008 2545 2559
3. R.R. Holman, S.K. Paul, M.A. Bethel, and et al. 10-Year follow-up of intensive glucose control in type 2 diabetes N Engl J Med 359 2008 1577 1589
4. R.A. Hayward, P.D. Reaven, W.L. Wiitala, and et al. Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes N Engl J Med 372 2015 2197 2206
5. S.E. Nissen, and K. Wolski Rosiglitazone revisited: an updated meta-analysis of risk for myocardial infarction and cardiovascular mortality Arch Intern Med 170 2010 1191 1201
6. J.J. McMurray, H.C. Gerstein, R.R. Holman, and et al. Heart failure: a cardiovascular outcome in diabetes that can no longer be ignored Lancet Diabetes Endocrinol 2 2014 843 851
7. Diabetes mellitus - evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes 2008 Department of Health and Human Services, Center for Drug Evaluation and Research Silver Spring, MD
8. European Medicines Agency guideline on clinical investigation of medicinal products in the treatment or prevention of diabetes mellitus 2012 Committee for Medicinal Products for Human Use London
9. J.A. Dormandy, B. Charbonnel, D.J. Eckland, and 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
10. ORIGIN Trial Investigators H.C. Gerstein, J. Bosch, and et al. Basal insulin and cardiovascular and other outcomes in dysglycemia N Engl J Med 367 2012 319 328
11. B.M. Scirica, D.L. Bhatt, E. Braunwald, and et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus N Engl J Med 369 2013 1317 1326
12. W.B. White, C.P. Cannon, S.R. Heller, and et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes N Engl J Med 369 2013 1327 1335
13. J.B. Green, M.A. Bethel, P.W. Armstrong, and et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes N Engl J Med 373 2015 232 242
14. M.A. Pfeffer, B. Claggett, R. Diaz, and et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome N Engl J Med 373 2015 2247 2257
15. B. Zinman, C. Wanner, J.M. Lachin, and et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes N Engl J Med 373 2015 2117 2128
16. M. Tonelli, P. Muntner, A. Lloyd, and et al. Risk of coronary events in people with chronic kidney disease compared with those with diabetes: a population-level cohort study Lancet 380 2012 807 814
17. C.S. Fox, K. Matsushita, M. Woodward, and et al. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis Lancet 380 2012 1662 1673
18. J.A. Udell, D.L. Bhatt, E. Braunwald, and et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes and moderate or severe renal impairment: observations from the SAVOR-TIMI 53 Trial Diabetes Care 38 2015 696 705
19. A.J. Scheen Pharmacodynamics, efficacy and safety of sodium-glucose co-transporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus Drugs 75 2015 33 59
20. G. Schernthaner, J.L. Gross, J. Rosenstock, and et al. Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea: a 52-week randomized trial Diabetes Care 36 2013 2508 2515
21. M.A. Abdul-Ghani, L. Norton, and R.A. DeFronzo Renal sodium-glucose cotransporter inhibition in the management of type 2 diabetes mellitus Am J Physiol Renal Physiol 309 2015 F889 F900
22. J.S. Yudkin, B. Richter, and E.A. Gale Intensified glucose lowering in type 2 diabetes: time for a reappraisal Diabetologia 53 2010 2079 2085
23. H.J. Lambers Heerspink, D. de Zeeuw, L. Wie, and et al. Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes Diabetes Obes Metab 15 2013 853 862
24. C.A. Emdin, K. Rahimi, B. Neal, and et al. Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis JAMA 313 2015 603 615
25. E. Grossman, P. Verdecchia, A. Shamiss, and et al. Diuretic treatment of hypertension Diabetes Care 34 Suppl 2 2011 May S313 S319
26. R. Klauser, R. Prager, S. Gaube, and et al. Metabolic effects of isradipine versus hydrochlorothiazide in diabetes mellitus Hypertension 17 1991 15 21
27. M.A. Weber, G.L. Bakris, K. Jamerson, and et al. ACCOMPLISH Investigators. Cardiovascular events during differing hypertension therapies in patients with diabetes J Am Coll Cardiol 56 2010 77 85
28. R. Chilton, I. Tikkanen, C.P. Cannon, and et al. Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes Diabetes Obes Metab 17 2015 1180 1193
29. A. Ceriello, S. Genovese, E. Mannucci, and et al. Understanding EMPA-REG OUTCOME Lancet Diabetes Endocrinol 3 2015 929 930
30. E. Ferrannini, E. Muscelli, S. Frascerra, and et al. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients J Clin Invest 124 2014 499 508
31. A. Merovci, C. Solis-Herrera, G. Daniele, and et al. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production J Clin Invest 124 2014 509 514
32. J.F. Williams, R.H. Childress, J.N. Chip, and et al. Hemodynamic effects of glucagon in patients with heart disease Circulation 39 1969 38
33. M.G. Bourassa, J. Eibar, and L. Campeau Effects of glucagon on myocardial metabolism in patients with and without coronary artery disease Circulation 42 1970 53 60
34. D.M. Nathan, J.B. Buse, M.B. Davidson, and et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes Diabetes Care 32 2009 193 203
35. G. Schernthaner, A.H. Barnett, D.J. Betteridge, and et al. Is the ADA/EASD algorithm for the management of type 2 diabetes (January 2009) based on evidence or opinion? A critical analysis Diabetologia 53 2010 1258 1269
36. S.E. Inzucchi, R.M. Bergenstal, J.B. Buse, and et al. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) Diabetologia 55 2012 1577 1596
37. S.E. Inzucchi, R.M. Bergenstal, J.B. Buse, and et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes Diabetes Care 38 2015 140 149
38. P.H. Groop, S. Del Prato, M.R. Taskinen, and et al. Linagliptin treatment in subjects with type 2 diabetes with and without mild-to-moderate renal impairment Diabetes Obes Metab 16 2014 560 568
39. G. Schernthaner, A.H. Barnett, S. Patel, and et al. Safety and efficacy of the dipeptidyl peptidase-4 inhibitor linagliptin in elderly patients with type 2 diabetes: a comprehensive analysis of data from 1331 individuals aged ≥ 65 years Diabetes Obes Metab 16 2014 1078 1086
40. J.L. Gross, C.K. Kramer, C.B. Leitão, and et al. Effect of antihyperglycemic agents added to metformin and a sulfonylurea on glycemic control and weight gain in type 2 diabetes: a network meta-analysis Ann Intern Med 154 2011 672 679
41. K. Esposito, P. Chiodini, G. Bellastella, and et al. Proportion of patients at HbA1c target <7% with eight classes of antidiabetic drugs in type 2 diabetes: systematic review of 218 randomized controlled trials with 78 945 patients Diabetes Obes Metab 14 2012 228 233
42. G. Schernthaner, and G.H. Schernthaner Glucose lowering therapy in type 2 diabetes: New hope after EMPA-REG OUTCOME trial HERZ 41 2016 208 216
43. E. Erdmann, J.A. Dormandy, B. Charbonnel, and et al. The effect of pioglitazone on recurrent myocardial infarction in 2,445 patients with type 2 diabetes and previous myocardial infarction: results from the PROactive (PROactive 05) Study J Am Coll Cardiol 49 2007 1772 1780
44. R. Wilcox, M.G. Bousser, D.J. Betteridge, and et al. Effects of pioglitazone in patients with type 2 diabetes with or without previous stroke: results from PROactive (PROspective pioglitAzone Clinical Trial In macro Vascular Events 04) Stroke 38 2007 865 873
45. G. Schernthaner, C.J. Currie, and G.H. Schernthaner Do we still need pioglitazone for the treatment of type 2 diabetes? A risk-benefit critique in 2013 Diabetes Care 36 Suppl 2 2013:S155:S161
46. W.N. Kernan, C.M. Viscoli, K.L. Furie, and et al. IRIS Trial Investigators. Pioglitazone after ischemic stroke or transient ischemic attack N Engl J Med 374 2016 1321 1331
47. R. Prager, G. Schernthaner, and H. Graf Effect of metformin on peripheral insulin sensitivity in non insulin dependent diabetes mellitus Diabete Metab 12 1986 346 350
48. A. Natali, and E. Ferrannini Effects of metformin and thiazolidinediones on suppression of hepatic glucose production and stimulation of glucose uptake in type 2 diabetes: a systematic review Diabetologia 49 2006 434 441
49. M.A. Abdul-Ghani, L. Norton, and R.A. Defronzo Role of sodium-glucose cotransporter 2 (SGLT 2) inhibitors in the treatment of type 2 diabetes Endocr Rev 32 2011 515 531
50. R. Roussel, F. Travert, B. Pasquet, and et al. Reduction of Atherothrombosis for Continued Health (REACH) Registry Investigators. Metformin use and mortality among patients with diabetes and atherothrombosis Arch Intern Med 170 2010 1892 1899
51. G. Schernthaner, and M.H. Schernthaner-Reiter Risk of metformin use in patients with T2DM and advanced CKD Nat Rev Endocrinol 11 2015 697 699
52. C. Wanner, J.M. Lachin, D.H. Fitchett, and et al. Empagliflozin and cardiovascular outcomes in patients with type 2 diabetes and chronic kidney disease JASN 26 Suppl B1 2015 113
53. C.A. Schneider, E. Ferrannini, R. Defronzo, and et al. Effect of pioglitazone on cardiovascular outcome in diabetes and chronic kidney disease J Am Soc Nephrol 19 2008 182 187
54. B.M. Scirica, E. Braunwald, I. Raz, and et al. Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial Circulation 130 2014 1579 1588
55. D.L. Weir, F.A. McAlister, A. Senthilselvan, and et al. Sitagliptin use in patients with diabetes and heart failure: a population-based retrospective cohort study JACC Heart Fail 2 2014 573 582
56. F. Zannad, C.P. Cannon, W.C. Cushman, and 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 385 2015 2067 2076
57. A.Z. Fu, S.S. Johnston, A. Ghannam, and et al. Association between hospitalization for heart failure and dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes: an observational study Diabetes Care 2016 Jan 6 pii: dc150764. [Epub ahead of print]
58. G. Schernthaner, A. Cahn, and I. Raz Is the use of DPP-4 inhibitors associated with an increased risk for heart failure - lessons from SAVOR, EXAMINE and TECOS Diabetes Care 2016 in press
59. K.B. Filion, L. Azoulay, R.W. Platt, and et al. A multicenter observational study of incretin-based drugs and heart failure N Engl J Med 374 2016 1145 1154
60. Food and Drug Administration. FDA Drug Safety Communication: FDA adds warnings about heart failure risk to labels of type 2 diabetes medicines containing saxagliptin and alogliptin. http://www.fda.gov/Drugs/DrugSafety/ucm486096.htm. Accessed 13.5.2016, 13:41.
61. Diabetes in Control. Victoza LEADER Trial Top-Line Results Announced. http://www.diabetesincontrol.com/victoza-leader-trial-top-line-results-announced/. Accessed 13.5.2016, 13:42.