Lack of clear evidence for metformin in type 2 diabetes on insulin therapy

Lack of clear evidence for metformin in type 2 diabetes on insulin therapy

Metformin is widely used as a first line treatment for type 2 diabetes and it is usually continued when treatment is intensified, such as with other oral agents or by insulin therapy. This systematic review looked at whether metformin is actually beneficial to patients who are using insulin.

Clinical question:

In people with type 2 diabetes, does treatment with metformin plus insulin as compared with insulin treatment alone lead to reduced mortality?

The reviewers looked at outcomes data for overall mortality and cardiovascular mortality.    Secondary outcomes included rates of complications, adverse events and glyaemic control.

The evidence:

The reviewers extracted and analysed data from 23 trials, comprising 2,117 participants.

For the primary outcomes there was so much uncertainty about the estimates of benefit that there is no benefit in reporting them.  This was due to the very low event rates in the trials.

However, glycaemic control, as measured by HbA1c, was significantly better with metformin and insulin when compared with insulin alone.  The mean difference was 0.60% (95% confidence interval −0.89% to −0.31%).

Appraisal hints:

Users of this research should consider:

  • The reviewers carried out a comprehensive search and rigorous evaluation of study quality.
  • They concluded that the trials in this area were of low methodological quality.
  • Patient-important outcomes were not well reported.  Many of the studies were too short for them to manifest themselves.
  • It seems likely that there would be important clinical heterogeneity between the studies.
  • We need higher quality, longer term studies in this area that focus on outcomes that are relevant to patients.


The full text of this paper is available from the BMJ:

Hemmingsen B, Christensen LL, Wetterslev J, Vaag A, Gluud C, Lund SS, Almdal T. Comparison of metformin and insulin versus insulin alone for type 2 diabetes: systematic review of randomised clinical trials with meta-analyses and trial sequential analyses. BMJ. 2012 Apr 19;344:e1771. doi: 10.1136/bmj.e1771.

Douglas Badenoch
I am an information scientist with an interest in making knowledge from systematic research more accessible to people who need it. This means you. I've been attempting this in the area of Evidence-Based Health Care since 1995. So far the results have been mixed. For some reason we expected busy clinicians to search databases and appraise papers instead of seeing patients. We also expected publishers to make the research freely available to the people who paid for it.. Ha! Hence The National Elf service.

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