Could Alzheimer’s disease (AD) be more accurately defined as diabetes type 3?

The idea that altered glucose metabolism in the central nervous system (CNS) could be at the core of AD has taken hold within the past decade.

Labeling AD as type 3 diabetes would not only reflect a new insight into pathophysiology

but it would also open up potential new treatment strategies.

What evidence is there in favor of a new nomenclature

Alzheimer’s Disease and Type 2 Diabetes

There is already a well-established link between AD and type 2 diabetes.

Diabetes-induced metabolic changes lead to oxidative damage and inflammation, resulting in protein damage and neuronal cell death in the CNS — ultimately contributing to AD. Additionally, there may be a common genetic link that predisposes some patients to develop both type 2 diabetes and AD.

According to a 2024 paper in Aging Research Reviews, “the brain was thought to be a tissue that was not sensitive to insulin,” and it was believed that the link between type 2 diabetes and AD is through vascular, inflammatory, or metabolic damage in the brain that occur as a result of altered systemic glucose metabolism.

However, as the paper notes, the contemporary thinking is that the brain is indeed an insulin-sensitive organ, a concept supported by the presence of receptors on neurons and glial cells such as GLUT-4 and IGF-1 that are involved in the uptake and metabolism of glucose in the brain. The authors also note insulin’s importance for “significant functions in neuronal circuitry formation, synaptic plasticity, dendritic arborization, neurotransmitter expression, neuronal survival, signal transduction and memory function.”

Proponents of the type 3 diabetes theory claim that the different effects of insulin in the brain, combined with alterations in glucose metabolism in the CNS likely trigger the other changes that we see in AD: accumulation of tau and amyloid beta proteins, hippocampal atrophy, and disordered neuronal communication.

• Glycolysis Genes and Diabetes Meds

There is evidence of a relationship between genes that control glycolysis in the brain itself and AD. In a 2025 study in Diabetes, Obesity and Metabolism, researchers found that several of the genes known to regulate glycolysis were downregulated in correlation with cognitive decline and severity of tau accumulation. Additionally, OVO-like zinc finger 2, which represses transcription of glycolysis-related genes, was up regulated in AD and also correlated with increased tau accumulation and low activity of glycolysis genes in the brain.

There are also data showing lower levels of AD in people taking diabetes medications.

A recent review published in Cells outlined how metformin may protect against neurodegenerative diseases, including AD. The authors suggest that the drug provides neuroprotection by “mechanisms beyond glucose control, including reduction of neuroinflammation, inhibiting microglial activation, combating oxidative stress, and strengthening the blood brain barrier.”

According to a population-based study published in the Journal of Alzheimer’s Disease this year, patients diagnosed with diabetes who took semaglutide — a GLP-1 receptor agonist — had a significantly lower risk of AD compared with patients who took other diabetes medications, including metformin and insulin

However, these studies did not examine whether AD was associated with altered glucose metabolism in the brain or whether this neurodegenerative disease is a comorbidity or a consequence of type 2 diabetes. We also don’t know if it would be safe to use diabetes medications in people at risk of AD who do not have diabetes.

• Are We There Yet?

Based on the existing evidence, we are not quite ready to switch from AD to type 3 diabetes.

Many patients with AD have never been diagnosed with diabetes, even at late stages of the neurodegenerative disease. 

The value of the type 3 diabetes concept is that it opens up new avenues of research and treatment. To date, treatment strategies for AD have focused on neuroprotection and reducing the accumulation of tau protein, amyloid beta. They have not yet been successful.

A key question is whether AD, a common condition that is diagnosed in patients based on clinical symptoms, has only one etiology that could explain the changes in the brain. Some theories have embraced a multifactorial etiology, which may include emotional stress, nutritional factors, poor overall health, or genetics as the ‘trigger.’ If glucose dysregulation is a trigger, that may allow us to diagnose earlier and ultimately stave off or delay neurodegeneration.

While much of the treatment to date has focused on removing proteins in the brain that are associated with AD, the ultimate goal would be to figure out how to prevent these proteins from accumulating in the first place.

Heidi Moawad, MD, is a neurologist and medical editor. She is on the teaching faculty at Case Western Reserve University.