Antidiabetic drugs for Alzheimer's and Parkinson's diseases: Repurposing insulin, metformin, and thiazolidinediones

Medical and scientific communities have been striving to disentangle the complexity of neurodegenerative diseases, particularly Alzheimer's disease (AD) and Parkinson's disease (PD), in order to develop a cure or effective treatment for these diseases. Along this journey, it has become important to identify the early events occurring in the prodromal phases of these diseases and the disorders that increase the risk of neurodegeneration highlighting common pathological features. This strategy has led to a wealth of evidence identifying diabetes, mainly type 2 diabetes mellitus (T2DM) as a main risk factor for the onset and progression of AD and PD. Impaired glucose metabolism, insulin resistance, and mitochondrial dysfunction are features common to both type 2 diabetes mellitus (T2DM), and AD and PD, and they appear before clinical diagnosis of the two neurodegenerative diseases. These could represent the strategic nodes of therapeutic intervention. Following this line of thought, a conceivable approach is to repurpose antidiabetic drugs as valuable agents that may prevent or reduce the risk of cognitive decline and neurodegeneration. This review summarizes the past and current findings that link AD and PD with T2DM, emphasizing the common pathological mechanisms. The efficacy of antidiabetic drugs, namely intranasal insulin, metformin, and thiazolidinediones, in the prevention and/or treatment of AD and PD is also discussed.