PPAR-γ Agonists May Have Benefits for Reducing Recurrent Stroke Risk

ischemic stroke
ischemic stroke
Higher-quality randomized controlled trials are needed in order to better assess the benefits of PPAR-γ agonists in recurrent stroke risk.

The use of peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists is likely effective in the treatment of type 2 diabetes as well as for reducing the risk for recurrent stroke, non-fatal myocardial infarction (MI), and cardiovascular death, according to a systematic review published in the The Cochrane Database of Systematic Reviews.

In this review, investigators searched for randomized controlled trials (RCTs) that compared PPAR-γ agonists (including balaglitazone, ciglitazone, darglitazone, edaglitazone, englitazone, glitazone, lobeglitazone, netoglitazone, pioglitazone, rivoglitazone, rosiglitazone, and troglitazone) with placebo in the prevention of recurrent stroke or vascular events in patients with stroke or transient ischemic attack (TIA). A total of 5 randomized controlled trials (RCTs) with 5039 patients were included in the analysis.

In 3 studies that reported recurrent stroke rates, PPAR-γ agonists reduced the risk for recurrent stroke compared with placebo (risk ratio (RR) 0.66; 95% CI, 0.44-0.99; moderate-quality evidence). Due to the wide confidence interval and high statistical heterogeneity of the study, the researchers were unable to ascertain whether PPAR-γ agonist-treated participants experienced more frequent adverse events compared with the placebo-treated group (risk difference 10%; 95% CI, –8%-28%; low-quality evidence).

Low-quality evidence from 1 study demonstrated that PPAR-γ agonists were associated with fewer serious vascular events; however, these data were not meta-analyzed. In addition, PPAR-γ agonists given over a 34.5-month period may reduce total events of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke (RR 0.73; 95% CI, 0.54 to 0.99; low-quality evidence).

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In another study assessing the effect of pioglitazone on insulin sensitivity, the PPAR-γ agonist resulted in a significantly greater change in the composite insulin sensitivity index compared with the placebo group (1.2 ± 0.6 vs -0.1 ± 0.6, respectively; P =.0003). Also, C-reactive protein levels decreased from 0.30 to 0.20 mg/L in patients receiving pioglitazone and increased from 0.41 to 0.45 mg/L in the placebo group (P =.06).

Additional high-quality unpublished studies may have been missed and not included in this meta-analysis, potentially limiting the findings.

The investigators suggested that higher-quality “double-blind RCTs with large sample sizes are required to test the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke” as well as the prevention of related vascular events for stroke or transient ischemic attack patients.


Liu J, Wang LN. Peroxisome proliferator-activated receptor gamma agonists for preventing recurrent stroke and other vascular events in people with stroke or transient ischaemic attack. Cochrane Database Syst Rev. 2017;12:CD010693.