GLP-1 Analogs, SGLT-2, and DPP-4 Inhibitors: A Triad of Hope for Alzheimer’s Disease Therapy

Abstract

Alzheimer’s is a prevalent, progressive neurodegenerative disease marked by cognitive decline and memory loss. The disease’s development involves various pathomechanisms, including amyloid-beta accumulation, neurofibrillary tangles, oxidative stress, inflammation, and mitochondrial dysfunction. Recent research suggests that antidiabetic drugs may enhance neuronal survival and cognitive function in diabetes. Given the well-documented correlation between diabetes and Alzheimer’s disease and the potential shared mechanisms, this review aimed to comprehensively assess the potential of new-generation anti-diabetic drugs, such as GLP-1 analogs, SGLT-2 inhibitors, and DPP-4 inhibitors, as promising therapeutic approaches for Alzheimer’s disease. This review aims to comprehensively assess the potential therapeutic applications of novel-generation antidiabetic drugs, including GLP-1 analogs, SGLT-2 inhibitors, and DPP-4 inhibitors, in the context of Alzheimer’s disease. In our considered opinion, antidiabetic drugs offer a promising avenue for groundbreaking developments and have the potential to revolutionize the landscape of Alzheimer’s disease treatment.

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.…”

Meta‐analysis on GLP‐1 mediated modulation of autophagy in islet β‐cells: Prospectus for improved wound healing in type 2 diabetes

“…Furthermore, Jung et al (2020) delved into the role of GLP‐1 in autophagy regulation within the context of insulin resistance 10 . Findings indicated that GLP‐1 receptor activation facilitated autophagy, offering a potential mechanism by which GLP‐1 agonists could alleviate insulin resistance, a hallmark of T2DM 10 …”

“…9 Furthermore, Jung et al (2020) delved into the role of GLP-1 in autophagy regulation within the context of insulin resistance. 10 Findings indicated that GLP-1 receptor activation facilitated autophagy, offering a potential mechanism by which GLP-1 agonists could alleviate insulin resistance, a hallmark of T2DM. 10 By influencing autophagy, GLP-1 receptor agonists may contribute to the preservation of islet β cells, thereby improving insulin secretion and cellular survival.…”

“…10 Findings indicated that GLP-1 receptor activation facilitated autophagy, offering a potential mechanism by which GLP-1 agonists could alleviate insulin resistance, a hallmark of T2DM. 10 By influencing autophagy, GLP-1 receptor agonists may contribute to the preservation of islet β cells, thereby improving insulin secretion and cellular survival. 7 This multifaceted action positions GLP-1 agonists not only as regulators of glucose but also as potential agents contributing to cellular health and homeostasis.…”

“…The multifaceted role of autophagy in cellular health and its potential link to wound healing outcomes underscore the importance of understanding how GLP‐1, a key player in glucose metabolism, may exert its effects through the modulation of this cellular process 16 . Insights gained from this meta‐analysis may not only contribute to a better understanding of the molecular mechanisms underlying GLP‐1's therapeutic effects but also pave the way for novel approaches aimed at enhancing wound healing in T2DM patients.…”