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Scope of new formulation approaches in the repurposing of pioglitazone for the management of Alzheimer’s disease

Alzheimer's disease (AD) is the most common cause of dementia among the elderly. The exact cause of the disease is not clearly known, and no existing therapies are able to prevent disease progression. Identification of the possible “impaired brain insulin signalling in AD” enriched the scope for “the repurposing of diabetic drugs in AD management.” Among the different classes of diabetic drugs, pioglitazone (PIO), a PPARγ agonist classed as an insulin sensitizer, is of the highest interest for AD management. The drug is reported to have direct action on multiple targets involved in AD, independent of insulin signalling. Even though PIO has appeared to be a potent molecule in preclinical trials, limited success was observed in the clinical stage. The tentative reasons for the limited therapeutic success in the clinical stage are not clear. The main focus of the review is to discuss various factors that might limit the therapeutic success of PIO in clinical trials and possible approaches to overcome those limitations.