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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

BMJ 2011; 343 doi: https://doi.org/10.1136/bmj.d4169 (Published 26 July 2011) Cite this as: BMJ 2011;343:d4169

Too many meta-analyses?

Boussageoun and colleagues [1] report the 9th meta-analysis [2-9] on
intensive glucose control in type 2 diabetes since the publication of 3
large, randomised controls trials (RCTs) in 2008-9 [10-12]. Their meta-
analysis included 10 RCTs. At best, the ratio of published RCTs to meta-
analyses (RCT:Met) [13] is 10/9 or 1.1. Three of the included RCTs [14-16]
had the same glycemic targets/strategies in both treatment arms so did not
compare intensive glycemic control with standard treatment, and another
included patients without diabetes [17]. Thus, at worst, the RCT:Met is
6/9 or 0.67.

Of the 10 RCTs included in the current meta-analysis, the 4 largest
RCTs [10-12, 18, 19] were included in all previous 8 meta-analysis, and
contributed approximately 80% of participants and events for the primary
endpoints in the current meta-analysis. Two small RCTs [20, 21] of
intensive treatment were included in 2 and 3 previous meta-analyses,
respectively. Of the 3 RCTs that did not compare intensive glycemic
control with standard treatment, 1 [14] was included in 5 previous meta-
analyses, and 2 [15, 16] were not included in any previous meta-analyses.
The remaining RCT [17] that included patients without diabetes was not
included in any previous meta-analysis. The two primary endpoints of the
current meta-analysis were included in all previous meta-analyses. Of the
secondary endpoints, the cardiovascular endpoints were included in between
5 and 8 of the previous meta-analyses, peripheral vascular endpoints in 2
meta-analyses, hypoglycaemia in 6 meta-analyses, and microvascular
endpoints in 1 meta-analysis. Therefore, it is difficult to see what
information the current meta-analysis adds to the 8 earlier meta-analyses,
nor how the results advance knowledge.

We have previously highlighted repeated meta-analyses of the same,
small number of RCTs in other fields [13, 22], and remain concerned at the
prominence given to such meta-analyses in medical journals. We suggest
that authors of meta-analysis should be required to demonstrate novelty,
important methodological improvements on previous meta-analyses, or
clinical equipoise before meta-analyses are published. At the very least,
no further trial-level meta-analyses of intensive glucose control in type
2 diabetes should be published unless further RCTs are carried out.

References:

1. Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M, Lafont S,
Bergeonneau C, Kassai B, et al. 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.
BMJ 2011;343:d4169.

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Competing interests: No competing interests

16 August 2011
Mark J Bolland
Senior Research Fellow
Andrew Grey
University of Auckland