No Clear Benefit for Tight Blood Glucose Control in T2DM

From Medscape Medical News

Laurie Barclay, MD

August 4, 2011 — Intensive glycemic control has no clear benefit vs conventional glycemic control for patients with type 2 diabetes, according to the results of a Cochrane systematic review reported online August 1 in the Cochrane Database of Systematic Reviews.
"Targeting the intensive levels means that many patients have to cope with complex and time consuming treatment," said lead author Bianca Hemmingsen, from the Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital in Copenhagen, Denmark, in a news release. "On top of this, they have the fear that their blood glucose might drop too low.... With the numbers of people in the world with type 2 diabetes increasing, it is important that we work out the best way of helping them to manage their blood glucose levels."
To compare outcomes when targeting intensive vs conventional glycemic control in patients with type 2 diabetes, the reviewers searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE, Science Citation Index Expanded, LILACS, and CINAHL (until December 2010) for randomized clinical trials comparing prespecified glycemic control targets in adults with type 2 diabetes. Determination of the risk for bias and data extraction was performed independently by 2 reviewers. Risk ratios (RRs) and 95% confidence intervals (CIs) were used to compare dichotomous outcomes.
The reviewers identified 20 trials in which a total of 16,106 adults with type 2 diabetes were randomly assigned to intensive glycemic control and 13,880 to conventional glycemic control. In each of the included trials, there were 20 to 11,140 participants, mean age 62.1 years, and the intervention lasted from 3 days to 12.5 years.
Mortality risk was not significantly different between the intensive and conventional glycemic control groups. For all-cause mortality, the RR was 1.01 (95% CI, 0.90 - 1.13; 29,731 participants, 18 trials), and for cardiovascular mortality, the RR was 1.06 (95% CI, 0.90 - 1.26; 29,731 participants, 18 trials). Using trial sequential analysis (TSA), the investigators demonstrated that a 10% reduction in RR could be refuted for all-cause mortality.
With use of a random-effects model, there was no significant effect of targeting intensive glycemic control on the risk for nonfatal myocardial infarction. However, in the fixed-effect model, there was a 14% reduction in risk (RR, 0.86; 95% CI, 0.78 - 0.96; P = .006; 29,174 participants, 12 trials).
Targeting intensive glycemic control was associated with a lower risk for amputation (RR, 0.64; 95% CI, 0.43 - 0.95; P = .03; n = 6960; 8 trials), a composite microvascular outcome (RR, 0.89; 95% CI, 0.83 - 0.95; P = .0006; n = 25,760; 4 trials), retinopathy (RR, 0.79; 95% CI, 0.68 - 0.92; P =.002; n = 10,986, 8 trials), retinal photocoagulation (RR, 0.77; 95% CI, 0.61 - 0.97; P = .03; n = 11,142; 7 trials), and nephropathy (RR, 0.78; 95% CI, 0.61 - 0.99; P = .04; n = 27,929; 9 trials).

Although targeting intensive glycemic control was associated with increased risks for mild and severe hypoglycemia, there was substantial heterogeneity among trials. In a subgroup analysis of trials studying glycemic control only in usual-care settings, there was a significant benefit of targeting intensive glycemic control for nonfatal myocardial infarction, but TSA showed that more trials are needed.

"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," the review authors write. "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."


Cochrane Database Syst Rev. 2011;6:CD008143.