Spence JD, et al. - Researchers assessed the impact of pioglitazone and the intention-to-treat effects of pioglitazone in prediabetes patients. In patients with stroke/transient ischemic attack and prediabetes, especially in those with good adherence, pioglitazone might be effective for secondary prevention.

Methods

• The IRIS study was a randomized multicenter clinical trial in patients with previous stroke or transient ischemic attack and insulin resistance, but not diabetes.
• From February 2005 to January 2013, patients were enrolled; median follow-up was 4.8 years.
• From June to September 2018, the post hoc analyses reported here were performed.
• Per American Diabetes Association criteria, prediabetes was characterized as having a hemoglobin A1c level of 5.7% to 6.4% or fasting plasma glucose level of 100 mg/dL to 125 mg/dL (to convert to mmol/L, multiply by 0.0555).
• Researchers defined good adherence as taking 80% or more of the protocol dose.
• Participants in the study were randomized to 15 mg of pioglitazone, with dose titrated to target of 45 mg daily, or matching placebo.
• Recurrent stroke or MI was the primary outcome; stroke, acute coronary syndrome, stroke/MI/hospitalization for heart failure, and progression to diabetes were included secondary outcomes.

Results

• Among 3,876 participants analyzed in the IRIS trial, 2,885 were involved in this analysis (1,456 in the pioglitazone cohort; 1,429 in the placebo cohort).
• It was noted that the mean (SD) age of patients was 64 (11) years, and 974 (66.9%) and 908 (63.5%) of patients were in the pioglitazone and placebo cohort, respectively.
• The hazard ratios (95% CI) were 0.57 (0.39-0.84) for stroke/MI, 0.64 (0.42-0.99) for stroke, 0.47 (0.26-0.85) for acute coronary syndrome, 0.61 (0.42-0.88) for stroke/MI/hospitalization for heart failure, and 0.18 (0.10-0.33) for progression to diabetes in the prediabetic population with good adherence (644 of 1,456 individuals [44.2%] in the pioglitazone group and 810 of 1,429 [56.7%] in the placebo group).
• The data presented in this work showed a nonsignificant reduction in overall mortality, cancer, and hospitalization, a slight increase in serious bone fractures, and an increase in weight gain and edema.
• Intention-to-treat outcomes also demonstrated significant reduction of events, though to a lesser degree.
• Investigators found that hazard ratios (95% CI) were 0.70 (0.56-0.88) for stroke/MI, 0.72 (0.56-0.92) for stroke, 0.72 (0.52-1.00) for acute coronary syndrome, 0.78 (0.63-0.96), for stroke/MI/hospitalization for heart failure, and 0.46 (0.35 to 0.61) for progression to diabetes.