Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials

Journal Title:	BMJ 2011-07-26, Vol.343 (7817), p.2070-d4169
Main Author:	Boussageon, Rémy
Other Authors:	Bejan-Angoulvant, Theodora , Saadatian-Elahi, Mitra , Lafont, Sandrine , Bergeonneau, Claire , Kassaï, Behrouz , Erpeldinger, Sylvie , Wright, James M , Gueyffier, François , Cornu, Catherine
Format:	Electronic Article
Language:	English
Subjects:	1600 Adult Adults Aged Albuminuria - etiology Albuminuria - mortality Blood Glucose - metabolism Cardiovascular diseases Cardiovascular System Cause of Death Clinical trials Clinical Trials (Epidemiology) Congestive heart failure Death Diabetes Diabetes mellitus Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - mortality Diabetic Angiopathies - drug therapy Diabetic Angiopathies - mortality Drugs Epidemiologic Studies Evidence-based medicine Female Glucose Health risk assessment Heart attacks Heart Failure Humans Hypoglycaemia Hypoglycemia Hypoglycemia - chemically induced Hypoglycemic Agents - therapeutic use Internet Ischaemic Heart Disease Life Sciences Male Meta-analysis Metabolic Disorders Microcirculation Microvasculature Middle Aged Mortality Myocardial infarction Myocardial Infarction - mortality Other Proteinurea Quantitative Research Randomized Controlled Trials as Topic Risk Reduction Behavior Statistical analysis Treatment Outcome Type 2 diabetes mellitus Urological Surgery Urology Young Adult
Publisher:	England: British Medical Journal Publishing Group
ID:	ISSN: 0959-8138
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title:	Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials
format:	Article
creator:	Boussageon, Rémy Bejan-Angoulvant, Theodora Saadatian-Elahi, Mitra Lafont, Sandrine Bergeonneau, Claire Kassaï, Behrouz Erpeldinger, Sylvie Wright, James M Gueyffier, François Cornu, Catherine
subjects:	1600 Adult Adults Aged Albuminuria - etiology Albuminuria - mortality Blood Glucose - metabolism Cardiovascular diseases Cardiovascular System Cause of Death Clinical trials Clinical Trials (Epidemiology) Congestive heart failure Death Diabetes Diabetes mellitus Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - mortality Diabetic Angiopathies - drug therapy Diabetic Angiopathies - mortality Drugs Epidemiologic Studies Evidence-based medicine Female Glucose Health risk assessment Heart attacks Heart Failure Humans Hypoglycaemia Hypoglycemia Hypoglycemia - chemically induced Hypoglycemic Agents - therapeutic use Internet Ischaemic Heart Disease Life Sciences Male Meta-analysis Metabolic Disorders Microcirculation Microvasculature Middle Aged Mortality Myocardial infarction Myocardial Infarction - mortality Other Proteinurea Quantitative Research Randomized Controlled Trials as Topic Risk Reduction Behavior Statistical analysis Treatment Outcome Type 2 diabetes mellitus Urological Surgery Urology Young Adult
ispartof:	BMJ, 2011-07-26, Vol.343 (7817), p.2070-d4169
description:	Objective To determine all cause mortality and deaths from cardiovascular events related to intensive glucose lowering treatment in people with type 2 diabetes.Design Meta-analysis of randomised controlled trials.Data sources Medline, Embase, and the Cochrane database of systematic reviews.Study selection Randomised controlled trials that assessed the effect of intensive glucose lowering treatment on cardiovascular events and microvascular complications in adults (≥18 years) with type 2 diabetes.Data extraction Primary end points were all cause mortality and death from cardiovascular causes. Secondary end points were severe hypoglycaemia and macrovascular and microvascular events.Synthesis of results Results are reported as risk ratios with 99% confidence intervals. Statistical heterogeneity between trials was assessed with χ², τ², and I2 statistics. A fixed effect model was used to assess the effect on the outcomes of intensive glucose lowering versus standard treatment. The quality of clinical trials was assessed by the Jadad score.Results 13 studies were included. Of 34 533 patients, 18 315 received intensive glucose lowering treatment and 16 218 standard treatment. Intensive treatment did not significantly affect all cause mortality (risk ratio 1.04, 99% confidence interval 0.91 to 1.19) or cardiovascular death (1.11, 0.86 to 1.43). Intensive therapy was, however, associated with reductions in the risk of non-fatal myocardial infarction (0.85, 0.74 to 0.96, P
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Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials

creator

Boussageon, Rémy ; Bejan-Angoulvant, Theodora ; Saadatian-Elahi, Mitra ; Lafont, Sandrine ; Bergeonneau, Claire ; Kassaï, Behrouz ; Erpeldinger, Sylvie ; Wright, James M ; Gueyffier, François ; Cornu, Catherine

creatorcontrib

description

Objective To determine all cause mortality and deaths from cardiovascular events related to intensive glucose lowering treatment in people with type 2 diabetes.Design Meta-analysis of randomised controlled trials.Data sources Medline, Embase, and the Cochrane database of systematic reviews.Study selection Randomised controlled trials that assessed the effect of intensive glucose lowering treatment on cardiovascular events and microvascular complications in adults (≥18 years) with type 2 diabetes.Data extraction Primary end points were all cause mortality and death from cardiovascular causes. Secondary end points were severe hypoglycaemia and macrovascular and microvascular events.Synthesis of results Results are reported as risk ratios with 99% confidence intervals. Statistical heterogeneity between trials was assessed with χ², τ², and I2 statistics. A fixed effect model was used to assess the effect on the outcomes of intensive glucose lowering versus standard treatment. The quality of clinical trials was assessed by the Jadad score.Results 13 studies were included. Of 34 533 patients, 18 315 received intensive glucose lowering treatment and 16 218 standard treatment. Intensive treatment did not significantly affect all cause mortality (risk ratio 1.04, 99% confidence interval 0.91 to 1.19) or cardiovascular death (1.11, 0.86 to 1.43). Intensive therapy was, however, associated with reductions in the risk of non-fatal myocardial infarction (0.85, 0.74 to 0.96, P<0.001), and microalbuminuria (0.90, 0.85 to 0.96, P<0.001) but a more than twofold increase in the risk of severe hypoglycaemia (2.33, 21.62 to 3.36, P<0.001). Over a treatment period of five years, 117 to 150 patients would need to be treated to avoid one myocardial infarction and 32 to 142 patients to avoid one episode of microalbuminuria, whereas one severe episode of hypoglycaemia would occur for every 15 to 52 patients. In analysis restricted to high quality studies (Jadad score >3), intensive treatment was not associated with any significant risk of reductions but resulted in a 47% increase in risk of congestive heart failure (P<0.001).Conclusions The overall results of this meta-analysis show limited benefits of intensive glucose lowering treatment on all cause mortality and deaths from cardiovascular causes. We cannot exclude a 9% reduction or a 19% increase in all cause mortality and a 14% reduction or a 43% increase in cardiovascular death. The benefit:risk ratio of intensive glucose lowering treatment in the prevention of macrovascular and microvascular events remains uncertain. The harm associated with severe hypoglycaemia might counterbalance the potential benefit of intensive glucose lowering treatment. More double blind randomised controlled trials are needed to establish the best therapeutic approach in people with type 2 diabetes.

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International edition

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0	ISSN: 0959-8138
1	ISSN: 0959-8146
2	ISSN: 0959-535X
3	ISSN: 0007-1447
4	EISSN: 1468-5833
5	EISSN: 1756-1833
6	DOI: 10.1136/bmj.d4169
7	PMID: 21791495
8	CODEN: BMJOAE

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eng

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England: British Medical Journal Publishing Group

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1600 ; Adult ; Adults ; Aged ; Albuminuria - etiology ; Albuminuria - mortality ; Blood Glucose - metabolism ; Cardiovascular diseases ; Cardiovascular System ; Cause of Death ; Clinical trials ; Clinical Trials (Epidemiology) ; Congestive heart failure ; Death ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - mortality ; Diabetic Angiopathies - drug therapy ; Diabetic Angiopathies - mortality ; Drugs ; Epidemiologic Studies ; Evidence-based medicine ; Female ; Glucose ; Health risk assessment ; Heart attacks ; Heart Failure ; Humans ; Hypoglycaemia ; Hypoglycemia ; Hypoglycemia - chemically induced ; Hypoglycemic Agents - therapeutic use ; Internet ; Ischaemic Heart Disease ; Life Sciences ; Male ; Meta-analysis ; Metabolic Disorders ; Microcirculation ; Microvasculature ; Middle Aged ; Mortality ; Myocardial infarction ; Myocardial Infarction - mortality ; Other ; Proteinurea ; Quantitative Research ; Randomized Controlled Trials as Topic ; Risk Reduction Behavior ; Statistical analysis ; Treatment Outcome ; Type 2 diabetes mellitus ; Urological Surgery ; Urology ; Young Adult

ispartof

BMJ, 2011-07-26, Vol.343 (7817), p.2070-d4169

rights

0	Boussageon et al 2011
1	Copyright: 2011 © Boussageon et al 2011
2	Distributed under a Creative Commons Attribution 4.0 International License
3	Boussageon et al 2011 2011 Boussageon et al

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1	Bejan-Angoulvant, Theodora
2	Saadatian-Elahi, Mitra
3	Lafont, Sandrine
4	Bergeonneau, Claire
5	Kassaï, Behrouz
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9	Cornu, Catherine

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creationdate	20110726
title	Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials
author	Boussageon, Rémy ; Bejan-Angoulvant, Theodora ; Saadatian-Elahi, Mitra ; Lafont, Sandrine ; Bergeonneau, Claire ; Kassaï, Behrouz ; Erpeldinger, Sylvie ; Wright, James M ; Gueyffier, François ; Cornu, Catherine

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55	Young Adult

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1	Bejan-Angoulvant, Theodora
2	Saadatian-Elahi, Mitra
3	Lafont, Sandrine
4	Bergeonneau, Claire
5	Kassaï, Behrouz
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1	Bejan-Angoulvant, Theodora
2	Saadatian-Elahi, Mitra
3	Lafont, Sandrine
4	Bergeonneau, Claire
5	Kassaï, Behrouz
6	Erpeldinger, Sylvie
7	Wright, James M
8	Gueyffier, François
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Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials

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PMCID: PMC3144314

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British Medical Journal Publishing Group

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21791495

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10.1136/bmj.d4169

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Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials