Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials.
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 chi(2) and I(2) statistics.


RESULTS
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 A(1c) concentration (HbA(1c)) 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).


CONCLUSIONS
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 HbA(1c) reduction might be different in differing populations.


BACKGROUND
None.
Ray
Kausik K
KK
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. kkr25@medschl.cam.ac.uk
Seshasai
Sreenivasa Rao Kondapally
SR
Wijesuriya
Shanelle
S
Sivakumaran
Rupa
R
Nethercott
Sarah
S
Preiss
David
D
Erqou
Sebhat
S
Sattar
Naveed
N
D001786:Blood Glucose / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D002423:Cause of Death; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000401:mortality / Q000517:prevention & control; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D016017:Odds Ratio; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012307:Risk Factors; D040242:Risk Reduction Behavior; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D001786:Blood Glucose; D006442:Glycated Hemoglobin