Hemmingsen B, Lund SS, Gluud C, Vaag A, Almdal T, Hemmingsen C, Wetterslev J, et al.
The Cochrane database of systematic reviews. Date of publication 2011 Jun 15;volume (6):CD008143.
1. Cochrane Database Syst Rev. 2011 Jun 15;(6):CD008143. doi:
10.1002/14651858.CD008143.pub2.
Targeting intensive glycaemic control versus targeting conventional glycaemic
control for type 2 diabetes mellitus.
Hemmingsen B(1), Lund SS, Gluud C, Vaag A, Almdal T, Hemmingsen C, Wetterslev J.
Author information:
(1)Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department
3344, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen,
Denmark, DK-2100.
Update in
Cochrane Database Syst Rev. 2013;11:CD008143.
BACKGROUND: Patients with type 2 diabetes mellitus (T2D) exhibit an increased
risk of cardiovascular disease and mortality compared to the background
population. Observational studies report a relationship between reduced blood
glucose and reduced risk of both micro- and macrovascular complications in
patients with T2D.
OBJECTIVES: To assess the effects of targeting intensive versus conventional
glycaemic control in T2D patients.
SEARCH STRATEGY: Trials were obtained from searches of CENTRAL (The Cochrane
Library), MEDLINE, EMBASE, Science Citation Index Expanded, LILACS, and CINAHL
(until December 2010).
SELECTION CRITERIA: We included randomised clinical trials that prespecified
different targets of glycaemic control in adults with T2D.
DATA COLLECTION AND ANALYSIS: Two authors independently assessed the risk of bias
and extracted data. Dichotomous outcomes were assessed by risk ratios (RR) and
95% confidence intervals (CI).
MAIN RESULTS: Twenty trials randomised 16,106 T2D participants to intensive
control and 13,880 T2D participants to conventional glycaemic control. The mean
age of the participants was 62.1 years. The duration of the intervention ranged
from three days to 12.5 years. The number of participants in the included trials
ranged from 20 to 11,140. There was no significant difference between targeting
intensive and conventional glycaemic control for all-cause mortality (RR 1.01,
95% CI 0.90 to 1.13; 29,731 participants, 18 trials) or cardiovascular mortality
(RR 1.06, 95% CI 0.90 to 1.26; 29,731 participants, 18 trials). Trial sequential
analysis (TSA) showed that a 10% RR reduction could be refuted for all-cause
mortality. Targeting intensive glycaemic control did not show a significant
effect on the risk of non-fatal myocardial infarction in the random-effects model
but decreased the risk in the fixed-effect model (RR 0.86, 95% CI 0.78 to 0.96; P
= 0.006; 29,174 participants, 12 trials). Targeting intensive glycaemic control
reduced the risk of amputation (RR 0.64, 95% CI 0.43 to 0.95; P = 0.03; 6960
participants, 8 trials), the composite risk of microvascular disease (RR 0.89,
95% CI 0.83 to 0.95; P = 0.0006; 25,760 participants, 4 trials), retinopathy (RR
0.79, 95% CI 0.68 to 0.92; P = 0.002; 10,986 participants, 8 trials), retinal
photocoagulation (RR 0.77, 95% CI 0.61 to 0.97; P = 0.03; 11,142 participants, 7
trials), and nephropathy (RR 0.78, 95% CI 0.61 to 0.99; P = 0.04; 27,929
participants, 9 trials). The risks of both mild and severe hypoglycaemia were
increased with targeting intensive glycaemic control but substantial
heterogeneity was present. The definition of severe hypoglycaemia varied among
the included trials; severe hypoglycaemia was reported in 12 trials that included
28,127 participants. TSA showed that firm evidence was reached for a 30% RR
increase in severe hypoglycaemic when targeting intensive glycaemic control.
Subgroup analysis of trials exclusively dealing with glycaemic control in usual
care settings showed a significant effect in favour of targeting intensive
glycaemic control for non-fatal myocardial infarction. However, TSA showed more
trials are needed before firm evidence is established.
AUTHORS' CONCLUSIONS: The included trials did not show significant differences
for all-cause mortality and cardiovascular mortality when targeting intensive
glycaemic control compared with conventional glycaemic control. Targeting
intensive glycaemic control reduced the risk of microvascular complications while
increasing the risk of hypoglycaemia. Furthermore, intensive glycaemic control
might reduce the risk of non-fatal myocardial infarction in trials exclusively
dealing with glycaemic control in usual care settings.
DOI: 10.1002/14651858.CD008143.pub2
PMID: 21678374 [Indexed for MEDLINE]
