The thiazolidinedione pioglitazone may prevent repeated cardiovascular events in persons who have insulin resistance but not diabetes mellitus (DM), suggesting a way to prevent stroke and myocardial infarction (MI) in patients at high risk who have already had 1 stroke or transient ischemic attack (TIA).
The results of the Insulin Resistance Intervention after Stroke (IRIS) trial suggest that a drug targeting cell metabolism may prevent secondary cardiovascular events even before DM develops.
“The IRIS trial supports the value of more research to test the vascular benefits of other interventions such as exercise, diet, and medications that have similar effects on metabolism as pioglitazone,” said lead author Walter N. Kernan, MD, professor of general medicine at Yale University School of Medicine, New Haven, CT.
Study results were published in the February 17, 2016 issue of the New England Journal of Medicine.
In this multicenter, double-blind trial, 3876 patients who had had a recent ischemic stroke or TIA and insulin resistance were randomly assigned to receive pioglitazone at a target dose of 45 mg/d or placebo.
At nearly 5 years follow-up, a stroke or MI occurred in 9% of patients taking pioglitazone and 11.8% of those receiving placebo—a 24% reduction.
Pioglitazone also reduced the risk of DM by 52% among the study participants but was associated with higher risks of weight gain, edema, and bone fracture requiring surgery or hospitalization.
Pioglitazone Plus Omega 3s
Also, pioglitazone combined with omega-3 fatty acids can improve lipid metabolism in patients who have type 2 DM and are receiving stable metformin therapy.
Omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are known to exert beneficial effects on the heart. European researchers recently evaluated the effects of a combination of EPA plus DHA and pioglitazone in overweight/obese patients with type 2 DM already treated with metformin.
A parallel-group, 4-arm, randomized trial included 69 patients who were assigned to a 24-week intervention using placebo; pioglitazone, 15 mg/d; EPA and DHA concentrate, 5 g/d); or pioglitazone plus EPA and DHA concentrate.
The study results were published in the December 2, 2015 issue of Nutrition and Metabolism.
Pioglitazone and pioglitazone plus omega-3 increased body weight and adiponectin levels. Both fasting glycemia and hemoglobin b A1c levels were increased by omega-3 but were unchanged by pioglitazone plus omega-3. Insulin sensitivity was not affected by omega-3, but it was improved by pioglitazone plus omega-3.
Fasting triacylglycerol concentrations and inflammatory markers were not affected significantly by any of the interventions. Lipid metabolism in the meal test and metabolic flexibility were additively improved by pioglitazone and omega-3.
The researchers concluded that “in spite of the modest negative effect of Omega-3 on glycemic control and postprandial glucose metabolism, no adverse effect on insulin sensitivity was observed.”
They suggested that clinicians advise typical patients with type 2 DM “to increase their EPA + DHA intake, either in the form of dietary supplements or sea food and fish, in order to increase the efficacy of pharmacotherapies and to prevent diseases linked to inflammation as well as cardiovascular disease, providing that glycemic control is closely monitored.”