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Cited by 803Diabetes Treatment and ManagementDiabetes Management and ResearchDiabetes, Cardiovascular Risks, and Lipoproteins

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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Boussageon, R., Bejan-Angoulvant, T., Saadatian-Elahi, M., Lafont, S., Bergeonneau, C., Kassai, B., Erpeldinger, S., Wright, J. M. +2 more·2011·BMJ
DOI 10.1136/bmj.d4169PMC PMC3144314
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Abstract

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 χ(2), τ(2), and I(2) 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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  1. Coutinho M, Wang Y, Gerstein HC, Yusuf S. The relationship between glucose and incident cardiovascular events. Diabetes Care 1999;22:233-40.

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Authors
Boussageon, R., Bejan-Angoulvant, T., Saadatian-Elahi, M., Lafont, S., Bergeonneau, C., Kassai, B., Erpeldinger, S., Wright, J. M., Gueyffier, F., & Cornu, C.
Affiliations
  • Lyon 1 Université (FR)
  • University of British Columbia (CA)
Corresponding author
Cornu, C.
ORCID
Venue
BMJ
Publisher
BMJ
Published
2011-07-26
Volume
343
Issue
jul26 1
Pages
d4169-d4169
ISSN
  • 0007-1447 (ISSN-L)
  • 0959-8138
  • 1468-5833
DOI
10.1136/bmj.d4169
PMC
PMC3144314
OpenAlex
W2115653936
Cited by
803
References
62
Citations by year
2026: 14 · 2025: 15 · 2024: 24 · 2023: 19 · 2022: 30 · 2021: 60 · 2020: 56 · 2019: 57 · 2018: 65 · 2017: 64 · 2016: 68 · 2015: 75 · 2014: 91 · 2013: 86 · 2012: 62
FWCI
11.24
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • BMJ (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • HighWire Press Open Archive (submittedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
type 2 diabetes, all-cause mortality, cardiovascular mortality, myocardial infarction, microalbuminuria, severe hypoglycemia, microvascular complications, HbA1c, number needed to treat, quality of evidence, Jadad score, trial heterogeneity, publication bias, risk of bias, meta-regression, subgroup analysis
MeSH terms
Adult, Aged, Albuminuria, Blood Glucose, Cause of Death, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Female, Humans, Hypoglycemia, Hypoglycemic Agents, Male, Microcirculation, Middle Aged, Myocardial Infarction, Randomized Controlled Trials as Topic, Treatment Outcome, Risk Reduction Behavior, Young Adult

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