Lower Dose of Insulin Drug Efficacious After Stroke, TIA

Lower doses of insulin-sensitizing drug, pioglitazone, after a stroke or transient ischemic attack may provide similar benefits to higher doses with a reduced risk of adverse events and outcomes.

Researchers conducted a randomized, double-blind trial that included individuals from the Insulin Resistance Intervention in Stroke trial. Participants were aged 40 years or older and had a stroke or transient ischemic attack within 6 months with no prior history of diabetes. Participants also must have had HbA1c levels of greater than 7% and insulin resistance with a HOMA-IR score greater than 3.0.

Participants were assigned to placebo or 1 of 4 doses of pioglitazone. Of the 1938 individuals who received pioglitazone, 546 participants received less than 15 mg/day, 128 received 15 mg/day, 89 received 30 mg/day, and 1175 received 45 mg/day.

The results indicated that the less than 15 mg/day group had no significant effect on stroke/myocardial infarction (MI) or new-onset diabetes. In the pooled analysis of 15 mg/day and 30 mg/day, the adjusted hazard ratios for stroke/MI were 0.48 compared with 0.74 for 45 mg/day. Similarly, the adjusted hazard ratios for new-onset diabetes were 0.34 and 0.31, respectively.

In patients taking less than 45 mg/day, the risk estimates for oedema, weight gain, and heart failure were lower. However, the risk of bone fractures with pioglitazone use was consistent across all doses.

“Lower doses of pioglitazone appear to confer much of the benefit with less adverse effects than the full dose,” researchers concluded. “Further study is needed to confirm these findings so that clinicians may optimize dosing of this secondary prevention strategy in patients with stroke”

—Leigh Precopio

Reference:

Spence JD, Viscoli C, Kernan WN, et al. Efficacy of lower doses of pioglitazone after stroke or transient ischemic attack in patients with insulin resistance. Diabetes Obes Metab. 2022;24(6):1150-1158. doi:10.1111/dom.14687