Can Semaglutide Treat Alzheimer’s Disease?

All eyes are on Novo’s blockbuster diabetes medicine and its potential role as a treatment for Alzheimer’s disease.

Has Semaglutide (Ozempic, Wegovy, or Rybelsus) been approved by the FDA for treating Alzheimer’s Disease?

The answer is “NO”. Semaglutide has not been approved for treating Alzheimer’s disease.

However, Semaglutide has been studied in individuals with Alzheimer’s disease and the results seem promising.

In fact, Alzheimer’s disease may be one more “off-label” use of Semaglutide.

We all know that semaglutide is available in three forms. Ozempic and Rybelsus are FDA-approved for the treatment of Diabetes while Wegovy has been approved for weight loss in obese individuals.

Apart from the FDA-approved indications, Semaglutide is used as an off-label treatment for the following conditions:

• PCOS (polycystic Ovarian Syndrome)
• Osteoarthritis in obese individuals
• Alcohol use disorder
• Fatty Liver (Non-alcoholic fatty liver disease)
• Weight loss in non-diabetics (Ozempic and Rybelsus)
• Chronic kidney disease and ASCVD (atherosclerotic cardiovascular disease)

Researchers are considering its use in individuals with Alzheimer’s disease because of its neuroprotective role in elderly patients.

Semaglutide Alzheimer’s Study: EVOKE Trial:

The EVOKE Trial is being conducted in individuals who are 55 to 85 years old with a mild degree of dementia and early-onset Alzheimer’s disease.

Amyloid positivity is confirmed via PET scan or CSF studies before enrolling the participants.

The study is expected to be completed in about 3 years (2026), however, preliminary data is positive. 

Participants in the study are being given Oral Semaglutide (Rybelsus) in a dose of 14 mg once daily vs a placebo medicine.

The study may be stopped prematurely if significant improvement is noted earlier compared to placebo.

The primary outcome of the EVOKE trial is to see how much a person’s memory, understanding, and ability to do everyday tasks change over the course of the study.

Different scoring systems are used in the EVOKE trial to assess Cognition and Functions.

Cognitive functions include:

• Memory,
• Orientation or knowing where you are,
• Judgment or making good decisions,
• Solving problems

Functions:

• Community affairs such as paying bills,
• Managing your home and hobbies, and
• Taking care of yourself.

By adding up the scores for these areas, they get a total score that tells them how much a person’s abilities have changed – the higher the total score, the bigger the change and the more the disease has affected them.

Different scores to assess Alzheimer’s progression are used including:

• Alzheimer’s Disease Cooperative Study Activities of Daily Living Scale for MCI (ADCS-ADLMCI) score
• 13-item Alzheimer’s Disease Assessment Scale
• Montreal Cognitive Assessment (MoCA) score 
• Alzheimer’s Disease Composite Score (ADCOMS)
• Mini-Mental State Examination (MMSE) score, and many more

Semaglutide Alzheimer Link: Is There Any Evidence?

GLP-1 use in diabetics has been linked to improvement in cognitive functions.

Preclinical data in human and animal studies have shown the neuroprotective roles of GLP-1 analogs including Exenatide, Lixisenatide, Liraglutide, and Dulaglutide [Ref].

There is a strong link between diabetes and Alzheimer’s disease. Diabetics are 1.6 times more likely to develop Alzheimer’s disease than non-diabetics.

GLP-1 analogs, Semaglutide in particular, may play a neuroprotective role by the following mechanisms  [Ref]:

• Reducing Neuroinflammation, neurofibrillary tangles, and amyloid plaques.
• Promoting neural progenitor cells
• Inhibiting inflammatory cytokines such as TNF-α
• Improving vascular function by removing intravascular atherosclerotic plaques
• Reducing glycated end-products

Other indirect mechanisms by which Semaglutide may improve symptoms of Alzheimer’s Disease include:

• a reduction in blood pressure
• reducing glycated hemoglobin
• reducing weight
• improving cardiovascular function

Neuroinflammation is one of the most important mechanisms underlying the development of Alzheimer’s disease. 

Semaglutide is said to suppress neuroinflammation and maintain vascular health.

Pooled data from 3 randomized controlled trials showed a significant reduction in the rates of dementia in patients who were on GLP-1 analogs vs placebo [Ref].

Alzheimer’s is Diabetes of the Brain:

Some folks now call Alzheimer’s disease “Type 3 Diabetes” It’s not exactly diabetes✌, though. It’s more like a way to describe how Alzheimer’s affects the brain.

In diabetes, high sugar levels harm blood vessels in the body. There is a gradual decline in kidney, heart, and pancreatic functions in diabetes.

In Alzheimer’s, amyloid plaques harm blood vessels and brain cells. So, both diseases have something in common when it comes to how they affect the body.

Furthermore, with age, people with diabetes develop more and more complications. These complications are not limited to the kidneys (Diabetic nephropathy), eyes (Retinopathy), or the peripheral nerves (Neuropathy).

The neurons of the brain are likely to get affected too. The occurrence of Diabetes Dementia (DD) Duo is on the rise as people with diabetes now live longer because of better diabetes medications and care.

People with dementia or Alzheimer’s are more likely to miss their medications and have uncontrolled diabetes and more complications.

Oral Semaglutide (Rybelsus) has revived the hope of stopping the progression of dementia and cognitive impairment, especially in diabetics.

Novo’s progress is expected to pave the way for further research, particularly exploring the potential of Mounjaro (Tirzepatide), Cagrisema (Cagrilintide Semaglutide), and Retatrutide, which promises to be intriguing.

“One Pill, Two Diseases: Semaglutide Treatment Delivers Double Impact”

If the EVOKE Trials confirm its effectiveness, Oral Semaglutide (Rybelsus 14 mg) could become a game-changer for individuals with diabetes and dementia.

While those with diabetes and Alzheimer’s stand to gain the most, even non-diabetics with Alzheimer’s may experience a slowdown in memory loss and cognitive decline.

The occurrence of the Diabetes Dementia (DD) Duo is on the rise as people enjoy longer lifespans.

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