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Pengyue Zhang, Chengsheng Mao, Anna Sun | Alzheimer s & Dementia | (2025)
Primary Link Archive Pubmed DOI Openalex Full text (OA)

Key Takeaways

Plain English Takeaway

People with type 2 diabetes who start certain diabetes medicines may have a lower chance of getting Alzheimer's disease, but more research is needed to prove if these medicines really help prevent it.

Study Aim

The study set out to examine whether starting treatment with glucagon-like peptide-1 (GLP-1) receptor agonists or sodium-glucose cotransporter-2 (SGLT-2) inhibitors, compared to dipeptidyl peptidase-4 (DPP-4) inhibitors, is linked to a lower risk of developing Alzheimer's disease (AD) in real-world patients. The authors wanted to see if these diabetes drugs might help prevent or delay AD, given their possible protective effects seen in earlier laboratory and animal studies. Simply put: The researchers wanted to find out if some diabetes drugs might lower the risk of Alzheimer's disease.

Study Design

The researchers used two large U.S. health databases: Optum Clinformatics (insurance claims) and Northwestern Medicine's electronic health records. They studied adults aged 60 and older who started taking GLP-1 receptor agonists, SGLT-2 inhibitors, or DPP-4 inhibitors. People with dementia or certain other diseases before starting these drugs were excluded. The team compared how often people developed Alzheimer's disease after starting each drug, using statistical models that adjusted for age, sex, race, weight, and other health conditions. They also ran extra analyses to check their results in different groups and with different methods. Simply put: The study looked at medical records to see if people who started certain diabetes drugs got Alzheimer's disease less often than those who took other diabetes drugs.

Findings

The study reveals that people who began treatment with GLP-1 receptor agonists or SGLT-2 inhibitors had a significantly lower risk of developing Alzheimer's disease compared to those who started DPP-4 inhibitors. This association was consistent across different groups, including women, White patients, and people with obesity. Specific drugs like liraglutide, semaglutide (GLP-1 receptor agonists), and dapagliflozin, canagliflozin, empagliflozin (SGLT-2 inhibitors) were also linked to reduced Alzheimer's risk. However, the study did not find consistent differences between GLP-1 receptor agonists and SGLT-2 inhibitors, nor did it find clear effects on Parkinson's disease. The authors caution that these results do not prove the drugs prevent Alzheimer's, and recommend clinical trials to confirm if these medicines truly help. Simply put: People who started certain diabetes drugs seemed less likely to get Alzheimer's, but more studies are needed to know if the drugs really protect the brain.

Abstract

INTRODUCTION: Glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors have potential beneficial effects in Alzheimer's disease (AD). METHODS: We conducted pharmacoepidemiologic studies using two large-scale real-world databases. We fitted covariate-adjusted Cox models to compare the risks of AD among initiators of GLP-1 receptor agonists, SGLT-2 inhibitors, and DPP-4 inhibitors. RESULTS: We identified GLP-1 receptor agonist initiation compared to DPP-4 inhibitors initiation was associated with a reduced risk of AD (hazard ratio [HR] ≤ 0.69 and P value < 0.001) and SGLT-2 inhibitor initiation compared to DPP-4 inhibitor initiation was associated with a reduced risk of AD (HR ≤ 0.67 and P value < 0.001). DISCUSSION: GLP-1 receptor agonist initiation and SGLT-2 inhibitor initiation are associated with a reduced risk of AD. Randomized clinical trials are warranted to validate the causal beneficial effects of GLP-1 receptor agonists and SGLT-2 inhibitors in AD. HIGHLIGHTS: Glucagon-like peptide-1 (GLP-1) receptor agonists are significantly associated with a reduced risk of Alzheimer's disease (AD) compared to dipeptidyl peptidase-4 (DPP-4) inhibitors. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are significantly associated with a reduced risk of AD compared to dipeptidyl peptidase-4 (DPP-4) inhibitors. Two GLP-1 receptor agonists (liraglutide and semaglutide) and three SGLT-2 inhibitors (dapagliflozin, canagliflozin, and empagliflozin) are associated with a reduced risk of AD in drug-specific sensitivity analyses.

Referenced In

William Fan
22 days ago
Neurodegenerative Diseases and Brain Aging

GLP-1s, Dementia, Alzheimer's, and Type 3 Diabetes

The suite of new GLP-1 agonists (GLP-1RAs) have shown a cascade of fascinating impacts, but the one that I have my eye on is this new idea that GLP-1 drugs may be preventative of brain aging diseases like Alzheimer's and Dementia.

GLP-1 is a naturally produced hormone in the human gut that regulates appetite and insulin secretion. The GLP-1 agonists drugs that have made a splash the last few years like semaglutide (Ozempic/Wegovy), liraglutide (Victoza/Saxenda), and dulaglutide (Trulicity), were originally developed for type 2 diabetes management.

But a 2026 Systematic Review found:

This study contributes to the clinical understanding of GLP-1 RAs and their effect on cognitive dysfunction. Findings from this study indicate GLP-1 RAs as potential therapeutics targeting cognitive function and neurocognitive disorders in persons living with T2DM.

This finding was echoed by a 2025 review which stated:

preclinical evidence has consistently shown the neuroprotective effects of GLP-1RAs, including reduced amyloid and tau pathology, improved synaptic function and enhanced neuronal survival

And a 2025 meta-analysis found that:

(GLP-1RAs) were associated with a statistically significant reduction in dementia

This finding was paired with a null result for the alternative cardio-protective glucose lowering agent sodium-glucose cotransporter-2 inhibitors (SGLT2is), suggesting the the GLP-1RAs are either using a unique pathway or are simply more effective. Contradictorily, a read world study released on the same day found benefits for both GLP-1RAs and SGLT2is; the meta-analysis may have been underpowered to detect SGLTis' benefits.

The link between Alzheimer's or Dementia and Diabetes is well known, with diabetes cited as a major risk factor. This is important to remember when contextualizing these findings as the population for the studies were almost all individuals with Type 2 Diabetes. That means we don't know if these neuroprotective effects can be generalized to people without T2D.

Interestingly as pointed out by the 2025 review, Alzheimer's and Dementia may be thought of as Type 3 Diabetes, as these diseases may be symptoms of underlying insulin dysregulation in the brain and damaged blood vessels. The tie between dementia and cardiovascular health echoes what we've heard in the past, that what's good for the heart is good for the brain. GLP-1 is naturally boosted by exercise and may point to the same correlation we see with exercise and brain health.

Excited to see how these findings pan out over the next few years, GLP-1RAs still require long term trials and reviews against the general population. The results for major trial targeting adults with early onset Alzheimer's released in March 2026 failed to show efficacy of oral semaglutide in reducing Alzheimer's. Note this study was funded by Novo Nordisk.

Oral semaglutide was not efficacious in slowing clinical progression in participants with early Alzheimer's disease.

This could be due to several reasons like the drug being more preventative than capable of reversing symptoms, weaker impacts of older generation GLP-1RAs or effects not being generalized outside of TD2 patients. But this is the strongest clinical result yet and points to the need for more trials before comprehensively marking success.

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