Impact of treatment with pioglitazone on stroke outcomes: A real-world database analysis

Aims: Randomized controlled trials have reported an association between pioglitazone and reduced incidence of stroke in type 2 diabetic (T2DM) and insulin-resistant populations. We investigated this association within a real-world database.

Materials and methods: T2DM patients who initiated pioglitazone between 2000 and 2012 were extracted from the Clinical Practice Research Datalink (CPRD), a UK routine data source. Two non-exposed control cohorts were matched according to age, gender, HbA1c, diabetes duration, stroke history, co-morbidities and prior T2DM regimen. Control cohort-1 comprised patients initiating a new T2DM therapy as their respective case initiated pioglitazone. Control cohort-2 maintained the same T2DM regimen as their respective case prior to the case initiating pioglitazone. Primary outcome was incident stroke; other outcomes included mortality, length of hospital stay and stroke recurrence.

Results: A total of 4234 patients initiating pioglitazone were matched to controls in cohort-1 and 3604 in cohort-2. For the primary outcome there were significantly reduced hazard ratios (HRs) for cases: controls. For cohort 1, the HR was 0.666 (95% CI, 0.466-0.952) during the therapy period and was 0.750 (0.612-0.919) over the entire observation period; for cohort 2, respective HRs were 0.516 (0.336-0.794) and 0.773 (0.611-0.978). There was no significant difference in 30-day mortality rate or rate of recurrent stroke. For stroke events that required hospitalization, there was a significant difference in length of stay for patients discharged to usual residence (median, 3.0 days vs 7.0 days; P = .008) for control cohort-2 while undergoing treatment.

Conclusions: In support of evidence from 2 large randomized trials, these observational data show that pioglitazone has a potent effect in reducing stroke events in patients with type 2 diabetes.