New research indicates that diabetes medications may be effective in combating Alzheimer’s disease and associated dementias.
A study published in JAMA Neurology shows that widely prescribed diabetes treatments, GLP-1RA and SGLT2i, substantially lower the risk of developing Alzheimer’s disease and related dementias.
As global life expectancy rises, so does the prevalence of dementia. Despite decades of intensive research, scientists have yet to discover a definitive treatment. Current therapies that slow dementia progression have not provided the breakthrough many hoped for.
Even when promising drugs are identified, it can take years to gather sufficient evidence supporting their efficacy. Bringing these medications to market also requires significant financial investment.
To expedite this process, some researchers are exploring the potential of existing, widely used medications to reduce dementia risk.
Recent studies suggest that type 2 diabetes and dementia share common physiological mechanisms, such as inflammation and impaired brain insulin signaling. Research has also confirmed that diabetes patients face a higher risk of developing dementia, raising questions about whether diabetes treatments could potentially reduce this risk.
The research team analyzed data from 92,160 type 2 diabetes patients aged 50 and older in Florida, Georgia, and Alabama.
Participants were monitored until they either passed away or developed dementia, including Alzheimer’s, vascular dementia, frontotemporal dementia, or Lewy body dementia.
The team compared the efficacy of diabetes medications in three combinations: glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus other secondary glucose-lowering agents, sodium-glucose co-transporter-2 inhibitors (SGLT2is) versus other secondary glucose-lowering agents, and GLP-1RA compared to SGLT2i.
Results showed that GLP-1RA reduced dementia risk by 33% compared to other secondary glucose-lowering agents, while SGLT2i lowered the risk by 43%.
While the exact mechanisms by which these diabetes medications lower dementia risk remain unclear, GLP-1RA has been shown to reduce neuroinflammation, improve brain insulin signaling, and promote neurogenesis.
SGLT2i may protect the brain by enhancing cerebral blood flow, reducing oxidative stress, and improving mitochondrial function.
Experts note that both GLP-1RA and SGLT2i help regulate blood sugar, reduce inflammation (a key factor in Alzheimer’s disease), and lower vascular risks associated with vascular dementia. They may also decrease levels of amyloid-beta and tau proteins in the brain.
However, another paper published in JAMA Neurology on the same day challenges these findings.
This study, a systematic review and meta-analysis of 26 clinical trials involving 164,531 participants, yielded different results.
While it confirmed that GLP-1RA significantly reduced the risk of dementia or cognitive impairment, SGLT2i did not show the same effect. This creates a conflicting narrative regarding SGLT2i potential in dementia prevention.
The discrepancy might be attributed to the relatively short observation periods in both studies, averaging less than five years, whereas dementia typically develops over a much longer time frame.
The researchers caution that it’s too early to draw definitive conclusions but suggest that using diabetes medications to manage insulin and inflammation might slow some brain changes associated with dementia.
This naturally leads to the question: Could diabetes medications help reduce dementia risk in people without diabetes?
The research team speculates that if the preventive mechanisms of GLP-1RA and SGLT2i involve reducing insulin resistance or inflammation, these medications might offer dementia prevention benefits even for individuals without diabetes.
While further long-term studies are needed to establish conclusive results, the hypothesis that diabetes medications, particularly GLP-1RA, could help reduce dementia risk in type 2 diabetes patients is generating significant interest in the medical community.
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