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Experts perspective on Pioglitazone

Dr. Elizabeth Paz-Pacheco of the Section of Endocrinology, Diabetes, and Metabolism of the University of the Philippines–Philippine General Hospital explained the United Kingdom Prospective Diabetes Study (UKPDS) showed that despite receiving the best standard of care, patients with type 2 diabetes mellitus suffered progressive deterioration of glycemic control over a period of 10 years.

“The UKPDS underscored the urgent need for alternative strategies that can address gaps in traditional diabetes therapies. Thiazolidinediones are worth considering because of their unique mechanism of action that targets the dual defects of type 2 diabetes mellitus: insulin resistance and beta cell dysfunction,” Dr. Pacheco said.

According to Dr. Pacheco, TZD interfere with the vicious cycle of obesity, hyperinsulinemia, and decreased adiponectin effects, which reducing peripheral insulin resistance. TZDs also reduce insulin resistance in the adipose tissues, she added. “By targeting the components of insulin resistance syndrome, TZDs subsequently improve the cardiovascular outcomes of patients with type 2 diabetes.”

Meanwhile, Dr. Rafael R. Castillo, past president of the Philippine Heart Association/Philippine College of Cardiology and the Philippine Society of Hypertension, emphasized in his lecture that diabetes is an established coronary heart disease equivalent and every effort must be made to improve the cardiovascular prognosis of diabetics.

“In patients with diabetes, a multifactorial intervention with multiple drug combinations and behavioral modification is essential to reduce heart attack and stroke, and improve survival,” stressed Dr. Castillo.

This multitarget intervention includes tight glucose regulation, optimal blood-pressure goals preferably achieved with renin-angiotensin system blockers, and the use of aspirin and lipid-lowering agents. Dr. Castillo added that the concomitant use of TZDs such as pioglitazone offers an attractive strategy not only for tighter glycemic control, but for incremental cardiovascular benefits on top of standard care for diabetics.

Furthermore, because TZDs effectively target insulin resistance, they are a promising therapeutic option in patients with non-alcoholic fatty liver disease (NAFLD), according to Dr. Diana Alcantara-Payawal, president of the Philippine Society of Gastroenterology and chief training officer of the Cardinal Santos Medical Center.

“Insulin resistance appears to play a central role in steatosis and non-alcoholic steatohepatitis [NASH]. With the well-established insulin-sensitizing effects of TZDs, this class of oral hypoglycemic agents can be used in treating NAFLD patients,” Dr. Payawal explained.

There has been keen interest among researchers on the potential therapeutic role of TZDs in NAFLD because of their effects on blood glucose, hepatic insulin sensitivity, adiponectin levels, hepatic fat content, inflammation, steatosis, and fibrosis. Dr. Payawal cited recent studies demonstrating how TZDs improved hepatic histology in patients with NASH. For instance, the study of Belfort and colleagues published in the New England Journal of Medicine stated that pioglitazone leads to histologic improvement and reversibility among patients with NAFLD. Moreover, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) showed significant decreases in this study. These results apply that insulin sensitizers, such as pioglitazone, in the treatment of NAFLD may improve insulin resistance and liver function.

Increased ALT concentrations predict the future development of type 2 diabetes and cardiovascular adverse events independently of other known risk factors. Indeed, increased liver enzymes are usually thought to be a consequence (and not a cause) of liver injury in NAFLD and can possibly be used as predictors of NAFLD progression.

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