Intensive glycaemic control does not reduce mortality in type 2 diabetes

Lots of different pills

More isn’t necessarily better.  This seems true in respect of glycaemic control in type 2 diabetes. More intensive control risks additional hypoglycaemia, where less intensive control risks long term complications.

An updated Cochrane systematic review looked at the impact of tighter or intensive glycaemic control on overall mortality.

Methods

Reading books

The reviewers extracted data from 28 randomised trials comparing intensive with less intensive glycemic control

The reviewers searched bibliographic databases, the Science Citation Index and clinical trials registers for randomised trials comparing intensive with less intensive glycemic control.  They had previously contacted manufacturers for unpublished data, but received none.

Outcomes data were extracted from these studies on overall mortality, cardiovascular mortality and major diabetes complications.

Study selection, assessment of the risk of bias and data extraction were performed by two blind, independent reviewers.

Results

28 studies were found involving 34,912 participants.

In pooling all this data, the reviewers concluded that intensive control increased the risk of mild and severe hypoglycaemia without improving mortality outcomes.

There was evidence that intensive glycaemic control may improve:

  • non-fatal myocardial infarction (RR 0.87, 95% CI 0.77 to 0.98)
  • amputation of a lower extremity (RR 0.65, 95% CI 0.45 to 0.94)
  • composite outcome of microvascular diseases (RR 0.88, 95% CI 0.82 to 0.95),
  • nephropathy (RR 0.75, 95% CI 0.59 to 0.95)
  • retinopathy (RR 0.79, 95% CI 0.68 to 0.92)
  • retinal photocoagulation (RR 0.77, 95% CI 0.61 to 0.97).

Comments

  • This was a well-conducted systematic review.
  • Studies differed in the exact glycemic targets used as “intensive” and “usual care” regimens.  However there wasn’t significant evidence of heterogeneity.
  • The reviewers felt that there was insufficient evidence to be sure of the effect on secondary outcomes above, or that these estimates may have been affected by bias.
  • This is a complex picture, where harm from over-treatment in some patients may be countering benefits in other patients.
  • The duration of trials may be significant for the mortality outcome.  Most of the trials were shorter than 2 years (over 95% of the participants).  Although the reviewers conducted a subgroup analysis to see if this affected the estimate of effect, there were too few participants in longer trials for the analysis to show an effect.

Reference

Hemmingsen B, Lund SS, Gluud C, Vaag A, Almdal TP, Hemmingsen C, Wetterslev J. Targeting intensive glycaemic control versus targeting conventional glycaemic control for type 2 diabetes mellitus. Cochrane Database of Systematic Reviews 2013, Issue 11. Art. No.: CD008143. DOI: 10.1002/14651858.CD008143.pub3.