Reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials.

<h4>Background</h4>The UK Prospective Diabetes Study showed that metformin decreases mortality compared to diet alone in overweight patients with type 2 diabetes mellitus. Since then, it has been the first-line treatment in overweight patients with type 2 diabetes. However, metformin-sul...

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Autores principales:	Rémy Boussageon, Irène Supper, Theodora Bejan-Angoulvant, Nadir Kellou, Michel Cucherat, Jean-Pierre Boissel, Behrouz Kassai, Alain Moreau, François Gueyffier, Catherine Cornu
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Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/099e18ead147466e9febdcd0e87c4740
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spelling	oai:doaj.org-article:099e18ead147466e9febdcd0e87c47402021-12-02T19:55:48ZReappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials.1549-12771549-167610.1371/journal.pmed.1001204https://doaj.org/article/099e18ead147466e9febdcd0e87c47402012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22509138/?tool=EBIhttps://doaj.org/toc/1549-1277https://doaj.org/toc/1549-1676<h4>Background</h4>The UK Prospective Diabetes Study showed that metformin decreases mortality compared to diet alone in overweight patients with type 2 diabetes mellitus. Since then, it has been the first-line treatment in overweight patients with type 2 diabetes. However, metformin-sulphonylurea bitherapy may increase mortality.<h4>Methods and findings</h4>This meta-analysis of randomised controlled trials evaluated metformin efficacy (in studies of metformin versus diet alone, versus placebo, and versus no treatment; metformin as an add-on therapy; and metformin withdrawal) against cardiovascular morbidity or mortality in patients with type 2 diabetes. We searched Medline, Embase, and the Cochrane database. Primary end points were all-cause mortality and cardiovascular death. Secondary end points included all myocardial infarctions, all strokes, congestive heart failure, peripheral vascular disease, leg amputations, and microvascular complications. Thirteen randomised controlled trials (13,110 patients) were retrieved; 9,560 patients were given metformin, and 3,550 patients were given conventional treatment or placebo. Metformin did not significantly affect the primary outcomes all-cause mortality, risk ratio (RR)=0.99 (95% CI: 0.75 to 1.31), and cardiovascular mortality, RR=1.05 (95% CI: 0.67 to 1.64). The secondary outcomes were also unaffected by metformin treatment: all myocardial infarctions, RR=0.90 (95% CI: 0.74 to 1.09); all strokes, RR=0.76 (95% CI: 0.51 to 1.14); heart failure, RR=1.03 (95% CI: 0.67 to 1.59); peripheral vascular disease, RR=0.90 (95% CI: 0.46 to 1.78); leg amputations, RR=1.04 (95% CI: 0.44 to 2.44); and microvascular complications, RR=0.83 (95% CI: 0.59 to 1.17). For all-cause mortality and cardiovascular mortality, there was significant heterogeneity when including the UK Prospective Diabetes Study subgroups (I(2)=41% and 59%). There was significant interaction with sulphonylurea as a concomitant treatment for myocardial infarction (p=0.10 and 0.02, respectively).<h4>Conclusions</h4>Although metformin is considered the gold standard, its benefit/risk ratio remains uncertain. We cannot exclude a 25% reduction or a 31% increase in all-cause mortality. We cannot exclude a 33% reduction or a 64% increase in cardiovascular mortality. Further studies are needed to clarify this situation.Rémy BoussageonIrène SupperTheodora Bejan-AngoulvantNadir KellouMichel CucheratJean-Pierre BoisselBehrouz KassaiAlain MoreauFrançois GueyffierCatherine CornuPublic Library of Science (PLoS)articleMedicineRENPLoS Medicine, Vol 9, Iss 4, p e1001204 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Rémy Boussageon Irène Supper Theodora Bejan-Angoulvant Nadir Kellou Michel Cucherat Jean-Pierre Boissel Behrouz Kassai Alain Moreau François Gueyffier Catherine Cornu Reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials.
description	<h4>Background</h4>The UK Prospective Diabetes Study showed that metformin decreases mortality compared to diet alone in overweight patients with type 2 diabetes mellitus. Since then, it has been the first-line treatment in overweight patients with type 2 diabetes. However, metformin-sulphonylurea bitherapy may increase mortality.<h4>Methods and findings</h4>This meta-analysis of randomised controlled trials evaluated metformin efficacy (in studies of metformin versus diet alone, versus placebo, and versus no treatment; metformin as an add-on therapy; and metformin withdrawal) against cardiovascular morbidity or mortality in patients with type 2 diabetes. We searched Medline, Embase, and the Cochrane database. Primary end points were all-cause mortality and cardiovascular death. Secondary end points included all myocardial infarctions, all strokes, congestive heart failure, peripheral vascular disease, leg amputations, and microvascular complications. Thirteen randomised controlled trials (13,110 patients) were retrieved; 9,560 patients were given metformin, and 3,550 patients were given conventional treatment or placebo. Metformin did not significantly affect the primary outcomes all-cause mortality, risk ratio (RR)=0.99 (95% CI: 0.75 to 1.31), and cardiovascular mortality, RR=1.05 (95% CI: 0.67 to 1.64). The secondary outcomes were also unaffected by metformin treatment: all myocardial infarctions, RR=0.90 (95% CI: 0.74 to 1.09); all strokes, RR=0.76 (95% CI: 0.51 to 1.14); heart failure, RR=1.03 (95% CI: 0.67 to 1.59); peripheral vascular disease, RR=0.90 (95% CI: 0.46 to 1.78); leg amputations, RR=1.04 (95% CI: 0.44 to 2.44); and microvascular complications, RR=0.83 (95% CI: 0.59 to 1.17). For all-cause mortality and cardiovascular mortality, there was significant heterogeneity when including the UK Prospective Diabetes Study subgroups (I(2)=41% and 59%). There was significant interaction with sulphonylurea as a concomitant treatment for myocardial infarction (p=0.10 and 0.02, respectively).<h4>Conclusions</h4>Although metformin is considered the gold standard, its benefit/risk ratio remains uncertain. We cannot exclude a 25% reduction or a 31% increase in all-cause mortality. We cannot exclude a 33% reduction or a 64% increase in cardiovascular mortality. Further studies are needed to clarify this situation.
format	article
author	Rémy Boussageon Irène Supper Theodora Bejan-Angoulvant Nadir Kellou Michel Cucherat Jean-Pierre Boissel Behrouz Kassai Alain Moreau François Gueyffier Catherine Cornu
author_facet	Rémy Boussageon Irène Supper Theodora Bejan-Angoulvant Nadir Kellou Michel Cucherat Jean-Pierre Boissel Behrouz Kassai Alain Moreau François Gueyffier Catherine Cornu
author_sort	Rémy Boussageon
title	Reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials.
title_short	Reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials.
title_full	Reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials.
title_fullStr	Reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials.
title_full_unstemmed	Reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials.
title_sort	reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/099e18ead147466e9febdcd0e87c4740
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Reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials.

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