Adverse cardiovascular events during treatment with pioglitazone and rosiglitazone: population based cohort studyBMJ 2009; 339 doi: https://doi.org/10.1136/bmj.b2942 (Published 19 August 2009) Cite this as: BMJ 2009;339:b2942
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The authors with this population based cohort study (1) have established
superiority of pioglitazone over rosiglitazone in terms of cardiovascular
adverse outcomes, although it appears to be a "class effect". The study
included elderly (more than 66 years of age), was of a considerable
duration (6 years), with large number of patients and so carry weight in
opinion making. We would like to add a word of caution in view of recent
adverse effects of thiazolidinediones (TZD) which have been reported
during the period studied by Juurlink et al.(1)
In recent years it has been reported that TZDs are associated with
increased incidence of fractures in women. The manufacturers of
pioglitazone, by 2007 have issued advisories regarding risk of fractures
to health professionals, based on clinical trial data outcomes. (2) The
impression over last few years have emerged that both men and women who
take TZDs for diabetes could be at increased risk of fractures over
distal upper and lower limb.(3,4,5) The fracture proportion increased with
The addition of black box warning to drug label by US Food and Drug
Administration with in few years after introduction of TZDs, withdrawal of
troglitazone from market due to rare cases of severe hepatotoxicity and
now, increased risk of fractures in both men and women irrespective of TZD
type has raised concern. Given the growing evidence of adverse outcomes,
do the benefits of TZDs still outweigh the risk has been questioned by
many. Should they be considered as appropriate first line therapy for type
This highlights need for rigorous post marketing surveillance
strategies for new drugs. Since elderly are more prone for falls, and
postmemopausal women for osteoporosis, caution must be exercised as far as
TZD use is concerned in advanced ages.
1. Juurlink DN, Gomes T, Lipscombe LL, Austin PC, Hux JE, Mamdani MM.
Adverse cardiovascular events during treatment with pioglitazone and
rosiglitazone: population based cohort study. BMJ 2009; 339: b2942.
2. Pioglitazone. WHO Pharmaceuticals newsletter 2007; 3: 5.
3. Dormuth CR, Carney G, Carleton B, Bassett K, Wright JM.
Thiazolidinediones and fractures in men and women. Arch Intern Med 2009;
4. Jones SG, Momin SR, Good MW, Shea TK, Patric K. Distal upper and
lower limb fractures associated with thiazolidinedione use. Am J Manag
Care 2009; 15: 491-496.
5. Loke YK, Sinkh S, Furberg CD. Long term use of thiazolidinediones
and fractures in type 2 diabetes: a meta-analysis. CMAJ 2009; 180: 32-39.
Competing interests: No competing interests