Abstract
For almost two decades, pioglitazone has been prescribed primarily to prevent and treat insulin resistance in some type 2 diabetic patients. In this review, we trace the path to discovery of pioglitazone as a thiazolidinedione compound, the glitazone tracks through the regulatory agencies, the trek to molecular agonism in the nucleus and the binding of pioglitazone to the nuclear receptor PPAR gamma. Given the rise in consumption of pioglitazone in T2D patients worldwide and the increased number of clinical trials currently testing alternate medical uses for this drug, there is also merit to some reflection on the reported adverse effects. Going forward, it is imperative to continue investigations into the mechanisms of actions of pioglitazone, the potential of glitazone drugs to contribute to unmet needs in complex diseases associated with the dynamics of adaptive homeostasis, and also the routes to minimizing adverse effects in every-day patients throughout the world.
Highlights
“I have discovered the great secret that after climbing a great hill, one only finds that there are many more hills to climb.”
Type 2 diabetes (T2D) is a chronic disease characterized by insulin resistance
The pharmacological approach to discovery of pioglitazone was aimed at uncoupling the lowering of blood glucose from the unwanted ensuing hypoglycemia that was characteristic of T2D medications at the time
Summary
“I have discovered the great secret that after climbing a great hill, one only finds that there are many more hills to climb.”. The reality of the World Health Organization demographics is sobering: over 90% of diabetics have T2D; a global obesity epidemic has ensured that T2D it is no longer solely an adult onset disease; and T2D will likely be the seventh leading cause of death in 20301. Pioglitazone and hPPARγ can be treated and managed in several ways throughout life Pioglitazone offers one such avenue that, like any medication, comes with risks and benefits. Pioglitazone is being evaluated globally, in over 50 clinical trials, for its potential use in unmet needs of several complex multifactorial diseases. 3clinicaltrials.gov potential of pioglitazone in modulating molecular mechanisms associated with adaptive homeostasis while balancing the risks and benefits of this medicine in real world patients with unmet clinical needs
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