Pharmacological Approaches Using Diabetic Drugs Repurposed for Alzheimer’s Disease

Abstract

Type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) are chronic, progressive disorders affecting the elderly, which fosters global healthcare concern with the growing aging population. Both T2DM and AD have been linked with increasing age, advanced glycosylation end products, obesity, and insulin resistance. Insulin resistance in the periphery is significant in the development of T2DM and it has been posited that insulin resistance in the brain plays a key role in AD pathogenesis, earning AD the name “type 3 diabetes”. These clinical and epidemiological links between AD and T2DM have become increasingly pronounced throughout the years, and serve as a means to investigate the effects of antidiabetic therapies in AD, such as metformin, intranasal insulin, incretins, DPP4 inhibitors, PPAR-γ agonists, SGLT2 inhibitors. The majority of these drugs have shown benefit in preclinical trials, and have shown some promising results in clinical trials, with the improvement of cognitive faculties in participants with mild cognitive impairment and AD. In this review, we have summarize the benefits, risks, and conflicting data that currently exist for diabetic drugs being repurposed for the treatment of AD.

Unlocking the Potential: Semaglutide’s Impact on Alzheimer’s and Parkinson’s Disease in Animal Models

“…This localized distribution in the hypothalamus is significant as it aligns with the proposed effects of SEM in the brain, such as neuroprotection. These effects are believed to be associated with the interaction of SEM with GLP-1 receptors in the brain [ 64 , 65 , 66 , 67 , 68 ]. This paradoxical finding underscores the complexity of SEM’s interaction with the brain and challenges the conventional understanding of its BBB permeability.…”

“…SEM has shown protective effects against the detrimental effects of Aβ25-35 on SH-SY5Y cells [ 35 ] and has also been found to activate the SIRT1/GLUT4 pathway [ 33 , 36 , 64 , 65 , 66 , 67 , 68 , 79 , 80 ].…”

Effects of antidiabetic agents on platelet characteristics with implications in Alzheimer's disease: Mendelian randomization and colocalization study

“…Due to sharing common characteristics with T2D, such as insulin resistance and impaired glucose control located in the cerebrum, AD was proposed as “type 3 diabetes” [ 8 ]. Therefore, antidiabetic agents have been highlighted as repurposing candidates for AD [ 9 , 10 ].…”