Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials

KK Ray, SRK Seshasai, S Wijesuriya, R Sivakumaran… - The Lancet, 2009 - thelancet.com
KK Ray, SRK Seshasai, S Wijesuriya, R Sivakumaran, S Nethercott, D Preiss, S Erqou
The Lancet, 2009thelancet.com
Background Whether intensive control of glucose reduces macrovascular events and all-
cause mortality in individuals with type 2 diabetes mellitus is unclear. We undertook a meta-
analysis of randomised controlled trials to determine whether intensive treatment is
beneficial. Methods We selected five prospective randomised controlled trials of 33 040
participants to assess the effect of an intensive glucose-lowering regimen on death and
cardiovascular outcomes compared with a standard regimen. We gathered information …
Background
Whether intensive control of glucose reduces macrovascular events and all-cause mortality in individuals with type 2 diabetes mellitus is unclear. We undertook a meta-analysis of randomised controlled trials to determine whether intensive treatment is beneficial.
Methods
We selected five prospective randomised controlled trials of 33 040 participants to assess the effect of an intensive glucose-lowering regimen on death and cardiovascular outcomes compared with a standard regimen. We gathered information about events of non-fatal myocardial infarction, coronary heart disease (fatal and non-fatal myocardial infarction), stroke, and all-cause mortality, and did a random-effects meta-analysis to obtain summary effect estimates for the clinical outcomes with use of odds ratios calculated from the raw data of every trial. Statistical heterogeneity across trials was assessed with the χ2 and I2 statistics.
Findings
The five trials provided information on 1497 events of non-fatal myocardial infarction, 2318 of coronary heart disease, 1127 of stroke, and 2892 of all-cause mortality during about 163 000 person-years of follow-up. The mean haemoglobin A1c concentration (HbA1c) was 0·9% lower for participants given intensive treatment than for those given standard treatment. Intensive glycaemic control resulted in a 17% reduction in events of non-fatal myocardial infarction (odds ratio 0·83, 95% CI 0·75–0·93), and a 15% reduction in events of coronary heart disease (0·85, 0·77–0·93). Intensive glycaemic control had no significant effect on events of stroke (0·93, 0·81–1·06) or all-cause mortality (1·02, 0·87–1·19).
Interpretation
Overall, intensive compared with standard glycaemic control significantly reduces coronary events without an increased risk of death. However, the optimum mechanism, speed, and extent of HbA1c reduction might be different in differing populations.
Funding
None.
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