Spotlight on thiazolidinediones

Some beneficial effects of rosiglitazone and pioglitazone were described by studies published in the last month.

In the first study, published by Annals of Neurology on June 30, researchers used observational data on 145,928 German patients age 60 or older between 2004 and 2010, all of whom were free of dementia at baseline. Diabetics who took pioglitazone for at least 8 calendar-year quarters had a 47% lower risk of dementia than the nondiabetics in the study (P=0.029), while those who took pioglitazone for a shorter time had a dementia risk comparable to nondiabetics, and diabetics who never took pioglitazone had a 23% increased risk of dementia (P<0.001). Rosiglitazone showed a similar, nonstatistically significant, trend, and the effects are biologically plausible, the study authors said, concluding that thiazolidinediones “may be effective as a preventive measure when taken prior to major pathological changes” in Alzheimer's disease, although this finding may apply only to diabetic patients. They noted that the study was limited by its observational nature and they called for prospective clinical trials.

The other study, published by Diabetes, Obesity and Metabolism on June 17, was a post hoc case-controlled time-dependent analysis of Veterans Affairs Diabetes Trial data, which included 1,791 patients with type 2 diabetes randomized to intensive or standard glycemic control and followed for 5 to 7.5 years. Patients who were randomized to rosiglitazone in the trial had a lower risk of cardiovascular events than those who didn't take the drug, this analysis found. A 4-mg daily dose was associated with an adjusted hazard ratio (HR) of 0.63 (95% CI, 0.49 to 0.81) and the 8-mg dose was associated with an adjusted HR of 0.60 (95% CI, 0.49 to 0.75) compared to nonuse. The risk of cardiovascular death was also reduced in patients on either dose. Myocardial infarction (MI) risk was slightly reduced on 8 mg and was not significantly affected by the 4-mg dose. The study authors note that this post hoc analysis provides weaker evidence than a prospective randomized controlled trial would. Specifically, it may be confounded by indication, as clinicians may have prescribed less rosiglitazone or stopped it sooner for patients with high cardiovascular risk or comorbidities; thus the low HRs associated with rosiglitazone could be partly explained by less healthy individuals being taken off the medication. The study's result differs from past meta-analyses, which suggested a higher risk of MI with rosiglitazone, but it is consistent with more recent evidence and “supports the recent FDA panel recommendations easing restrictions on rosiglitazone,” the study authors said, and they recommended the results be interpreted with caution as other concerns about adverse events with thiazolidinediones remain, so risks and benefits should be balanced.