No difference between TZDs and DPP-4 inhibitors or sulphonylureas added to metformin in type 2 diabetes

No difference between TZDs and DPP-4 inhibitors or sulphonylureas added to metformin in type 2 diabetes

Research question:

In people with type 2 diabetes inadequately controlled with metformin, which additional oral therapy offers the greatest improvement in HbA1c?

The reviewers just looked at glycaemic control in patients whose starting HbA1c was 7% or higher at 12 weeks or longer follow-up.

The evidence:

Eight randomised trials were found, which looked at various combinations of treatments.  Meta-analysis was conducted by calculating a pooled mean difference in HbA1c.

  • TZDs versus DPP-4 inhibitors (2 RCTs, n=753):  No significant difference in HbA1c.
  • TZDs versus sulphonylureas (4 RCTs, n=1,711):  No significant difference in HbA1c.

Appraisal hints:

  • It’s not clear when the search was performed.
  • One would expect to find more than eight studies for this topic area.  However, the reviewers limited themselves to studies that directly compared additional oral therapies being added to metformin treatments.  They excluded 78 studies that compared additional treatments with placebo, or that included patients who had previously been treated with regimens other than metformin alone.  This is a large body of evidence to rule out of the reckoning.
  • There was some evidence of heterogeneity between the studies.
  • Subgroup analysis by patient type is essential to assist clinical practice.


Poolsup N, Suksomboon N, Setwiwattanakul W. Efficacy of various antidiabetic agents as add-on treatments to metformin in type 2 diabetes mellitus: systematic review and meta-analysis. ISRN Endocrinol. 2012;2012:798146. Epub 2012 Mar 27.

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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