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Therapeutics Initiative Department of Anesthesiology, Pharmacology and Therapeutics University of British Columbia Burnaby, British Columbia, Canada
Therapeutics Initiative Department of Anesthesiology, Pharmacology and Therapeutics University of British Columbia
Therapeutics Initiative Fraser Health Pharmacy Services Burnaby Hospital Pharmacy University of British Columbia 3935 Kincaid Street Burnaby BC V5G 2X6 fax 604/412-6187 Aaron.tejani{at}fraserhealth.ca
Published Online, February 3, 2009. www.theannals.com, DOI 10.1345/aph.1K666a
In our opinion, neither pioglitazone nor rosiglitazone should be prescribed at all, as both increase cardiovascular morbidity, arguably the most important clinical outcome that oral hypoglycemic drugs are designed to reduce. In the case of rosiglitizone, if anything, mortality is increased.2
Khanderia et al. neglected the Richter et al.3 meta-analysis, which found that in 22 trials of at least 24 weeks' duration, patients randomized to receive pioglitazone were more likely to develop edema and heart failure than were those on placebo (6% vs 4%, respectively), including heart failure leading to hospitalization. While the incidence of heart failure increased, diabetic patients gained no associated benefit to justify the cardiovascular risk. Richter et al. concluded that "published studies of at least 24 weeks of pioglitazone treatment in people with type 2 diabetes mellitus did not provide convincing evidence that patient-oriented outcomes...are positively influenced by this compound."
In addition, Richter et al. state that total serious adverse event rates were comparable between pioglitazone and other drugs/placebo, which implies that there is neither a net benefit nor net harm associated with pioglitazone. Lincoff et al.4 did not report total serious adverse events; however, they did report on a nonsignificant difference on a subset of serious adverse events, namely death/myocardial infarction (MI)/stroke/and heart failure. Again, this implies that pioglitazone does not produce any benefit compared with other drugs/placebo with respect to serious morbidity and mortality.
Khanderia et al. also imply that a patient on rosiglitazone who is achieving glycemic targets and not experiencing complications should remain on the drug. If these trials and meta-analyses of TZDs show anything conclusively, it is that the attainment of glycemic targets is not associated with any clinical benefit (and in the case of rosiglitazone, has a net harmful effect). The fact that Khanderia et al. consider the increase in MI with rosiglitazone "extremely small" could be accepted if there was any evidence of benefit to offset this harm. However, this is not the case.
Another meta-analysis by Richter et al.5 provides the best insights into the net harm from rosiglitazone. They found that total serious adverse events (which include mortality and cardiovascular and other serious morbidity) occurred in 6% of patients on rosiglitazone compared with 4% of patients on other interventions (metformin, sulfonylureas, placebo).
In conclusion, current randomized controlled trial evidence demonstrates net harm for TZD therapy in type 2 diabetes.
References
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