Loke et al cursorily entertain the alternative postulate that
pioglitazone yields cardiovascular benefits, but readily dismiss it.
However, this is an equally plausible explanation of the analysis, given
that it is a comparison between pioglitazone and rosiglitazone rather than
placebo or control therapy. There is moderate evidence that the composite
endpoint of death, myocardial infarction and stroke is reduced by
pioglitazone in high risk vascular patients (PROactive study HR 0.84 CI
0.72-0.98) (1) and lower risk patients (HR 0.75 CI 0.55-1.02) which, when
combined (n=16390 patients) results in an 18% reduction (HR 0.82 CI 0.72-
0.94, p=0.005) (2). Furthermore, the reduced rate of progression of
coronary atherosclerosis associated with pioglitazone, compared with
glimepiride, in the PERISCOPE study, is also compelling evidence for its
beneficial cardiovascular effects (3).
The order of magnitude of rosiglitazone's harmful vascular effect
compared to pioglitazone (14-22%), as assessed by Loke et al, is similar
to that of pioglitazone's beneficial effect compared to control therapy.
It therefore seems unreasonable to unilaterally interpret the findings
negatively towards rosiglitazone where they could equally be interpreted
positively for pioglitazone, avoiding further demonization of
rosiglitazone. It is nevertheless appreciated that class adverse effects
of the PPAR gamma agonists, such as non-fatal congestive heart failure,
apply generally to all agents in this class of drugs.
1. Dormandy JA, Charbonnel B, Eckland DJA, et al. Secondary
prevention of macrovascular events in patients with type 2 diabetes in the
PROactive Study (PROspective pioglitAzone Clinical Trial in macroVascular
Events): a randomised controlled trial. Lancet 2005; 366(9493): 1279-
1289
2. Lincoff AM, Wolski K, Nicholls SJ, et al. Pioglitazone and risk
of cardiovascular events in patients with type 2 diabetes mellitus: a
meta-analysis of randomized trials. JAMA 2007; 298(10): 1180-1188
3. Nissen SE, Nicholls SJ, Wolski K, et al. Comparison of
pioglitazone vs glimepiride on progression of coronary atherosclerosis in
patients with type 2 diabetes: the PERISCOPE randomized controlled trial.
JAMA 2008; 299(13): 1561-1573
Rapid Response:
Demonization of rosiglitazone
Dear Editor,
Loke et al cursorily entertain the alternative postulate that
pioglitazone yields cardiovascular benefits, but readily dismiss it.
However, this is an equally plausible explanation of the analysis, given
that it is a comparison between pioglitazone and rosiglitazone rather than
placebo or control therapy. There is moderate evidence that the composite
endpoint of death, myocardial infarction and stroke is reduced by
pioglitazone in high risk vascular patients (PROactive study HR 0.84 CI
0.72-0.98) (1) and lower risk patients (HR 0.75 CI 0.55-1.02) which, when
combined (n=16390 patients) results in an 18% reduction (HR 0.82 CI 0.72-
0.94, p=0.005) (2). Furthermore, the reduced rate of progression of
coronary atherosclerosis associated with pioglitazone, compared with
glimepiride, in the PERISCOPE study, is also compelling evidence for its
beneficial cardiovascular effects (3).
The order of magnitude of rosiglitazone's harmful vascular effect
compared to pioglitazone (14-22%), as assessed by Loke et al, is similar
to that of pioglitazone's beneficial effect compared to control therapy.
It therefore seems unreasonable to unilaterally interpret the findings
negatively towards rosiglitazone where they could equally be interpreted
positively for pioglitazone, avoiding further demonization of
rosiglitazone. It is nevertheless appreciated that class adverse effects
of the PPAR gamma agonists, such as non-fatal congestive heart failure,
apply generally to all agents in this class of drugs.
1. Dormandy JA, Charbonnel B, Eckland DJA, et al. Secondary
prevention of macrovascular events in patients with type 2 diabetes in the
PROactive Study (PROspective pioglitAzone Clinical Trial in macroVascular
Events): a randomised controlled trial. Lancet 2005; 366(9493): 1279-
1289
2. Lincoff AM, Wolski K, Nicholls SJ, et al. Pioglitazone and risk
of cardiovascular events in patients with type 2 diabetes mellitus: a
meta-analysis of randomized trials. JAMA 2007; 298(10): 1180-1188
3. Nissen SE, Nicholls SJ, Wolski K, et al. Comparison of
pioglitazone vs glimepiride on progression of coronary atherosclerosis in
patients with type 2 diabetes: the PERISCOPE randomized controlled trial.
JAMA 2008; 299(13): 1561-1573
Competing interests: No competing interests