Insulinosensibilisateurs (metformine/glitazones) : niveau de preuve et controverse

[en] Summary Because of the deleterious role attributed to insulin resistance, insulin sensitizing agents should theoretically reduce the incidence of cardiovascular complications in type 2 diabetes. In the UKPDS, metformin reduced the risk of myocardial infarction and cardiovascular mortality in a rather small group of recently diagnosed patients at a low cardiovascular risk. These results deserve confirmation in a larger study with patients a high cardiovascular risk. Glitazones, as more specific insulin sensitizers, raised much hope. However, rosiglitazone fell from its pedestal after the suspicion of an increased risk of myocardial infarction. In PROactive among patients at high cardiovascular risk, pioglitazone gave positive but questionable results: statistical significance was not reached regarding the large composite primary endpoint, but well regarding the prespecified more focused principal secondary endpoint or in various post-hoc analyses. Thus, even if data with insulin sensitizers appear globally rather promising, evidence is rather weak, therefore leading to recurrent controversy.
[fr] Résumé Au vu du rôle délétère de l’insulinorésistance, un médicament insulino-sensibilisateur devrait normalement réduire l’incidence des complications cardiovasculaires du diabète de type 2. Dans l’étude UKPDS, la metformine a réduit le risque d’infarctus du myocarde et la mortalité cardiovasculaire chez des ptients récemment diagnostiqués et à faible risque, résultats qui mériteraient d’être confirmés chez des patients à haut risque cardiovasculaire. Les glitazones (des agents insulinosensibilisateurs plus spécifiques) avaient suscité beaucoup d’espoirs. Cependant la rosiglitazone est tombée de son piédestal après la suspicion d’une augmentation du risque coronarien (non réellement prouvé). Dans PROactive, conduite chez des patients à haut risque cardiovasculaire, la pioglitazone a donné des résultats discutables : la signification statistique n’était pas atteinte pour le principal critère d’évaluation composite étendu, mais bien pour le critère secondaire principal restreint pré-spécifié ou dans des analyses post-hoc. Ainsi, si les données disponibles apparaissent plutôt favorables concernant les insulino- sensibilisateurs, les preuves sont fragiles, d’où la controverse récurrente.

Disciplines :

Pharmacy, pharmacology & toxicology
Endocrinology, metabolism & nutrition

Author, co-author :

SCHEEN, André ; Centre Hospitalier Universitaire de Liège - CHU > Diabétologie,nutrition, maladies métaboliques

Language :

French

Title :

Insulinosensibilisateurs (metformine/glitazones) : niveau de preuve et controverse

Alternative titles :

[en] Insulin sensitizers (metformin/glitazones): Level of evidence and controversy

Publication date :

December 2015

Journal title :

Médecine des Maladies Métaboliques

ISSN :

1957-2557

eISSN :

2214-8477

Publisher :

Masson, Issy-les-Moulineaux, France

Special issue title :

Journée thématique 2015 de la société francophone du diabète ( SFD)

Volume :

Pages :

759-767

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 18 December 2015

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Bibliography

R.A. DeFronzo Banting Lecture. From thetriu-mvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus Diabetes 58 2009 773 795
G.M. Reaven Banting Lecture 1988. Role of insulin resistance in human disease Diabetes 37 1988 1595 1607
R.A. DeFronzo, and E. Ferrannini Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and athero-sclerotic cardiovascular disease Diabetes Care 14 1991 173 194
A.J. Scheen, and B. Charbonnel Effects of glucose-lowering agents on vascular outcomes in type 2 diabetes: a critical reappraisal Diabetes Metab 40 2014 176 185
Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes, (UKPDS., 34)., UK., Prospective Diabetes Study (UKPDS), Group Lancet 352 1998 854 865
[Erratum in: Lancet 1998;352:1558]
M. Foretz, B. Guigas, L. Bertrand, and et al. Metformin: from mechanisms of action to therapies Cell Metab 20 2014 953 966
H. Yki-Järvinen Thiazolidinediones N Engl J Med 351 2004 1106 1118
J.A. Dormandy, B. Charbonnel, D.J. Eckland, and et al. PROactive investigators. 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
S.E. Nissen, and K. Wolski Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes N Engl J Med 356 2007 2457 2471
[Erratum in: N Engl J Med 2007;357:100]
A.M. Lincoff, J.C. Tardif, G.G. Schwartz, and et al. AleCardio Investigators. 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
S.E. Inzucchi, R.M. Bergenstal, and J.B. Buse Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes Diabetologia 58 2015 429 442
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
R. Boussageon, I. Supper, T. Bejan-Angoulvant, and et al. Reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-ana-lysis of randomised controlled trials PLoS Med 9 2012 e1001204
D.R. Cryer, S.P. Nicholas, D.H. Henry, and et al. Comparative outcomes study of metformin intervention versus conventional approach: the COSMIC Approach Study Diabetes Care 28 2005 539 543
A. Kooy, J. de Jager, P. Lehert, and et al. Long-term effects of metformin on metabolism and micro-vascular and macrovascular disease in patients with type 2 diabetes mellitus Arch Intern Med 169 2009 616 625
L.G. Mellbin, K. Malmberg, A. Norhammar, and et al. DIGAMI 2 Investigators. Prognostic implications of glucose-lowering treatment in patients with acute myocardial infarction and diabetes: experiences from an extended follow-up of the Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Study Diabetologia 54 2011 1308 1317
J.A. Johnson, S.R. Majumdar, S.H. Simpson, and E.L. Toth Decreased mortality associated with the useof metformin compared with sulfonylurea monotherapy in type 2 diabetes Diabetes Care 25 2002 2244 2248
I. Tzoulaki, M. Molokhia, V. Curcin, and 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 data-base BMJ 339 2009 b4731
C.L. Roumie, A.M. Hung, R.A. Greevy, and et al. Comparative effectiveness of sulfonylurea and metformin monotherapy on cardiovascular events in type 2 diabetes mellitus: a cohort study Ann Intern Med 157 2012 601 610
C.L. Morgan, J. Mukherjee, S. Jenkins-Jones, and et al. Association between first-line monotherapy with sulphonylurea versus metformin and risk of all-cause mortality and cardiovascular events: a retrospective, observational study Diabetes Obes Metab 16 2014 957 962
C.H. Chang, Y.C. Chang, J.W. Lin, and et al. Cardiovascular risk associated with acarbose versus metformin as the first-line treatment in patients with type 2 diabetes: a nationwide cohort study J Clin Endocrinol Metab 100 2015 1121 1129
N.M. Scheller, U.M. Mogensen, C. Andersson, and et al. All-cause mortality and cardiovascular effects associated with the DPP-IV inhibitor sita-gliptin compared with metformin, a retrospective cohort study on the Danish population Diabetes Obes Metab 16 2014 231 236
R. Roussel, F. Travert, B. Pasquet, and et al. Reduction of Atherothrombosis for Continued Health (REACH) registry. Metformin use and mortality among patients with diabetes and atherothrombosis Arch Intern Med 170 2010 1892 1899
A.J. Scheen, and N. Paquot Metformin revisited: a critical review of the benefit-risk balance in at-risk patients with type 2 diabetes Diabetes Metab 39 2013 179 190
E. Selvin, S. Bolen, H.C. Yeh, and et al. Cardiovascular outcomes in trials of oral diabetes medications: a systematic review Arch Intern Med 168 2008 2070 2080
C. Lamanna, M. Monami, N. Marchionni, and E. Mannucci Effect of metformin on cardiovascular events and mortality: a meta-analysis of randomized clinical trials Diabetes Obes Metab 13 2011 221 228
B. Hemmingsen, L.L. Christensen, J. Wetterslev, and et al. Comparison of metformin and insulin versus insulin alone for type 2 diabetes: systematic review of randomised clinical trials with meta-analyses and trial sequential analyses BMJ 344 2012 e1771
A.J. Scheen Outcomes and lessons from the PROactive study Diabetes Res Clin Pract 98 2012 175 186
E. Erdmann, J.A. Dormandy, B. Charbonnel, and et al. PROactive Investigators. 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
R. Wilcox, M.G. Bousser, D.J. Betteridge, and et al. PROactive Investigators. 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
J.M. Seong, N.K. Choi, J.Y. Shin, and et al. Differential cardiovascular outcomes after dipeptidyl pepti-dase-4 inhibitor, sulfonylurea, and pioglitazone therapy, all in combination with metformin, for type 2 diabetes: a population-based cohort study PLoS One 10 2015 e0124287
N. Ziyadeh, A.T. McAfee, C. Koro, and et al. The thiazolidinediones rosiglitazoneand pioglitazone and the risk of coronary heart disease: a retrospective cohort study using a US health insurance database Clin Ther 31 2009 2665 2677
A.M. Lincoff, K. Wolski, S.J. Nicholls, and S.E. Nissen Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials JAMA 298 2007 1180 1188
E. Mannucci, M. Monami, C. Lamanna, and et al. Pioglitazone and cardiovascular risk. A compre-hensive meta-analysis of randomized clinical trials Diabetes Obes Metab 10 2008 1221 1238
G. Schernthaner, and R.J. Chilton Cardiovascular risk and thiazolidinediones - what do meta-analyses really tell us? Diabetes Obes Metab 12 2010 1023 1035
P.D. Home, S.J. Pocock, H. Beck-Nielsen, and et al. RECORD Study Team. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial Lancet 373 2009 2125 2135
M. Komajda, J.J. McMurray, H. Beck-Nielsen, and et al. Heart failure events with rosiglitazone in type 2 diabetes: data from the RECORD clinical trial Eur Heart J 31 2010 824 831
R.G. Bach, M.M. Brooks, M. Lombardero, and et al. BARI 2D Investigators. Rosiglitazone and outcomes for patients with diabetes mellitus and coronary artery disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial Circulation 128 2013 785 794
R. Loebstein, M. Dushinat, J. Vesterman-Landes, and et al. Database evaluation of the effects of long-term rosiglitazone treatment on cardiovascular outcomes in patients with type 2 diabetes J Clin Pharmacol 51 2011 173 180
C.C. Wang, W.L. Chen, T.W. Kao, and et al. Incidence of cardiovascular events in which 2 thiazolidinediones are used as add-on treatments for type 2 diabetes mellitus in a Taiwanese population Clin Ther 33 2011 1904 1913
[Erratum in: Clin Ther 2012;34:508]
Y.K. Loke, C.S. Kwok, and S. Singh Comparative cardiovascular effects of thiazolidinediones: systematic review and meta-analysis of observational studies BMJ 342 2011 d1309
X. Chen, L. Yang, and S.D. Zhai Risk of cardiovascular disease and all-cause mortality among diabetic patients prescribed rosiglitazone or pioglitazone: a meta-analysis of retrospective cohort studies Chin Med J (Engl) 125 2012 4301 4306
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
E. Mannucci, M. Monami, M. Di Bari, and et al. Cardiac safety profile of rosiglitazone: a com-prehensive meta-analysis of randomized clinical trials Int J Cardiol 143 2010 135 140
Y. Lu, D. Ma, W. Xu, and et al. Effect and cardiovascular safety of adding rosiglitazone to insulin therapy in type 2 diabetes: A meta-analysis J Diabetes Investig 6 2015 78 86
J.C. Stone, L. Furuya-Kanamori, J.J. Barendregt, and S.A. Doi Was there really any evidence that rosiglitazone increased the risk of myocardial infarction or death from cardiovascular causes? Pharmacoepidemiol Drug Saf 24 2015 223 227
D.I. Bromage, and D.M. Yellon The pleiotropic effects of metformin: time for prospective studies Cardiovasc Diabetol 14 2015 109
J.D. Lewis, L.A. Habel, C.P. Quesenberry, and et al. Pioglitazone use and risk of bladder cancer and other common cancers in persons with diabetes JAMA 314 2015 265 277
A.J. Scheen Gliptines, sécurité cardio-vasculaire et insuffisance cardiaque: le point après l'étude TECOS Rev Med Suisse 11 2015 1526 1531
B. Zinman, C. Wanner, J.M. Lachin, and et al. EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes N Engl J Med 2015 Sep 17 [Epub ahead of print]
A.J. Scheen Exenatide once weekly in type 2 diabetes Lancet 372 2008 1197 1198