Pioglitazone after Ischemic Stroke or Transient Ischemic Attack

Ischemic stroke or transient ischemic attack (TIA) patients are at increased risk for future cardiovascular events. Interestingly, the identification of insulin resistance has been discovered as a risk factor for stroke and myocardial infarction. The resistance of insulin as a risk factor raised the possibility that pioglitazone might benefit patients with cerebrovascular disease. Pioglitazone, which is normally used in patients with Diabetes, improves insulin sensitivity; therefore, Pioglitazone could possibly help with the insulin resistance associated with cardiovascular complications.

In this article, the authors focused on a particular study using the treatment of pioglitazone in patients who had a recent ischemic stroke or TIA. It was a multi center, double-blind trial using 3876 randomly assigned patients. The patients were either treated with pioglitazone (target dose of 45 mg daily) or a placebo. There were 1939 patients in the pioglitazone group and 1937 in the placebo group. The patients involved in the study were not diagnosed with Diabetes, but were found to have insulin resistance based on the HOMA-IR, or homeostasis model assessment of insulin resistance, index.

After 1 year, the HOMA-IR index was lower in the pioglitazone group than in the placebo group. The results after 4.8 years of this study are as follows: A primary outcome (stroke or myocardial infarction) had occurred in 9.0% of the pioglitazone group and in 11.8% of the placebo group. Diabetes developed in 3.8% of the pioglitazone group as compared to 7.7% of the placebo group. Also, pioglitazone was associated with a higher frequency of weight gain (52.2%), edema (35.6%), and bone fracture requiring surgery or hospitalization (5.1%).

In conclusion, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received the placebo. Pioglitazone was also associated with a lower risk of diabetes, but with a higher risk of some of the side effects, such as weight gain, edema, and fracture.

 

http://www.nejm.org/doi/full/10.1056/NEJMoa1506930#t=article

Kernan, Walter N., Viscoli, Catherine M., Furie, Karen L., et al. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. N Engl J Med. 2016.

Modulation of Cell-Mediated Immunity to Suppress High Fat Diet-Induced Obesity and Insulin Resistance

This study was designed to test the effects that cyclosporine A and fingolimod may have on obesity caused by high fat diets and insulin resistance.  This study was conducted in mice that were fed a high fat diet, and that were regularly injected for fifteen weeks with cyclosporine A, fingolimod, or a control.

The study begins by validating its importance due to the large spike in American obesity.  The study reported that 34.9% of American adults are considered obese.  Cyclosporine A is used in organ transplant patients to help prevent the immune system from rejecting the organ.  Fingolimod, on the other hand, is used as a first-line defense in patients experiencing a relapsing form of multiple sclerosis.

Of the mice, those injected with cyclosporine A had an average body weight that was 34% less than the control mice.  Those mice treated with fingolimod were about 16% less in body weight.  They found that the cyclosporine A mice maintained weight gain suppression throughout the entire experiment, while the fingolimod mice had slowed weight gain after week 7.  To rule out the thought that there could be lean mass being lost a body composition analysis was completed using EchoMRI.  It was found that the lean mass of the mice was unaffected, but the cyclosporine A mice had 60.8% less fat mass than the control.  The fingolimod mice had about 22.2% less fat mass than the control mice.

The results of this study were that cyclosporine A and fingolimod both were able to suppress weight gain, improve the mice’s sensitivity to insulin, and reduce their hepatic fat accumulation.  It concluded that this is a promising option that should continue to be looked into and developed.

Pharmacists see countless patients suffering from diabetes type 2 and other weight related conditions.  How would an injection like this affect the way pharmacists discussed lifestyle changes and nutrition expert recommendations?  Do you feel there would be a push from patients to receive the shot rather than make changes similar to the pressure physicians feel to prescribe antibiotics?

 

Pharm Res.  2016;33(2):395-403.