Electronic letters to:

Research:
Yoon K. Loke, MBBS MD, Sonal Singh, MD MPH, and Curt D. Furberg, MD PhD
Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis
CMAJ 2009; 180: 32-39 [Abstract] [Full text] [PDF]
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[Read eLetter] Long-term use of thiazolidinediones and fractures in type 2 diabetes: a reappraisal of evidence
Konstantinos A. Toulis   (22 December 2008)

Long-term use of thiazolidinediones and fractures in type 2 diabetes: a reappraisal of evidence 22 December 2008
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Konstantinos A. Toulis
Aristotle University of Thessaloniki

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Re: Long-term use of thiazolidinediones and fractures in type 2 diabetes: a reappraisal of evidence

touliskos{at}gmail.com Konstantinos A. Toulis

KA Toulis, DG Goulis, AD Anastasilakis

By means of a meta-analysis, Loke and colleagues provided evidence that long- term thiazolidinedione use is associated with a higher fracture risk, suggesting that the latter is significant among women, but not men, after appropriate within-study data stratification [1]. However, broad inclusion criteria used (any thiazolidinedione in treatment group, any active comparator or placebo in the control group) and absence of subgroup analyses could have resulted in missing potentially important clinical implications.

In fact, re-analyzing data presented on the basis of the actual treatment used (rosiglitazone or pioglitazone), patients with type II diabetes demonstrated evidence of significant fracture risk when treated with rosiglitazone compared to controls [four studies, fixed-effects pooled odds ratio (95% confidence interval) 1.64 ( 1.24, 2.17), I2 = 21%,], whereas no significant difference in fracture risk was found between pioglitazone-treated patients and control groups [six studies, fixed-effects pooled OR (95% CI) 1.26 (0.92, 1.71), I2 = 22%] (http://www.wi-not.com/meta/figureA.jpg, http://www.wi- not.com/meta/figureB.jpg). Indirect comparison between the two thiazolidinedione groups was not feasible, because no common comparator existed [2].

After within-study data stratification on sex, pooled odds ratio was estimable only for pioglitazone-treated patients (relevant data for rosiglitazone were available in only one study). Women on pioglitazone demonstrated evidence of significant fracture risk [four studies, fixed- effects pooled OR (95% CI) 2.14 (1.33, 3.44), I2 = 13%]; however, this finding was not durable to sensitivity analysis using random effects model [pooled OR (95% CI) 2.00 (0.86, 4.66)] (http://www.wi- not.com/meta/figureC.jpg). As expected, men treated with pioglitazone did not demonstrate evidence of significant fracture risk compared to controls [four studies, fixed-effects pooled OR (95% CI) 0.84 (0.53, 1.34), I2 = 0%]. In summary, re-analysis of evidence suggested that pioglitazone use might not be associated with increased fracture risk neither in women nor in men with type 2 diabetes. This finding has both clinical and research implications.

References

1. Loke YK, Singh S, Furberg CD Long-term use of thiazolidinediones and fractures in type 2 diabetes: systematic review and meta-analysis. CMAJ 2009;180(1). DOI:10.1503/cmaj.080486

2. Song F, Altman DG, Glenny AM, Deeks JJ. Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses. BMJ. 2003; 326:472

HTML version: http://www.wi-not.com/meta/index.html

Conflict of Interest:

None declared