
Ozempic found to be better than approved therapies at slashing risk of disease affecting 7M Americans
Diabetes has long been linked to dementia, with an increased risk of around 70 percent, due to high blood sugar levels that can damage vessels supplying blood to the brain, blocking the flow of oxygen.
Traditionally, metformin has been used as a first line therapy for diabetes due to its established safety profile and cost-effectiveness, costing less than $25 per month for a typical dose.
And recent studies found that it also helped to improve cognition and lower dementia or Alzheimer's risk in people with type 2 diabetes.
However, the medication, prescribed 80 million times in the US annually, is known to cause a variety of side effects, including diarrhea, stomach ache and loss of appetite.
Vitamin B12 deficiency is also a common side effect of taking metformin in higher doses or for long periods, with tiredness, muscle weakness, mouth ulcers and vision problems being among chief complaints.
Now, a new study led by Taiwan-based Professor Szu Yuan Wu and published in the open access journal BMJ Open Diabetes Research & Care, suggests GLP-1 receptor agonists might be a more effective remedy to safeguard against dementia than metformin by up to 25 percent.
These type of drugs were also associated with lower death rates than metformin.
GLP-1s - which mimic the effects of the hormone that stimulates insulin release, suppressing glucagon, and slowing stomach emptying - also have a range of other benefits including significant weight loss, improved blood sugar control, and potential cardiovascular benefits.
But they too come with negative side effects, including vomiting, mood changes and vision problems.
The researchers believe the new findings could help shape future clinical guidelines for the treatment of type 2 diabetes, especially with GLP-1 medication costs decreasing due to market competition.
In the new study, the researchers drew on anonymized electronic health records from a global health research network (Trinetx) spanning the period 2004 to 2024 to track the development of dementia in patients with type 2 diabetes.
The patients had been treated with either GLP-1s or metformin (there were 87,229 patients in each group with an average age of 58) for at least six consecutive months.
From the data, the researchers found that GLP-1 drugs were associated with a significantly lower (10 percent) risk of developing dementia, overall, with an incidence of about 2.5 percent compared with an incidence of nearly five percent for metformin.
And specifically, taking this type of drug was associated with a 12 percent lower risk of developing Alzheimer's disease, and a 25 percent lower risk of developing other non-vascular dementias than metformin use.
Further in-depth analyses showed that these positive effects were evident across all age groups, but with the strongest effect among people over 60, women, and those of White ethnicity.
Risk of death from any cause was also lower.
Nearly five percent of those treated with GLP-1 receptor agonists died compared with nearly nine percent of those treated with metformin.
With metformin, the researchers note that the benefits primarily derive through a variety of metabolic processes that impact the entire body.
These include reducing glucose production in the liver, increasing insulin sensitivity, and influencing gut health.
Meanwhile, GLP-1 receptor agonists exert direct effects on the central nervous system by crossing the blood-brain barrier.
This allows them to act on GLP-1 receptors within the brain, influencing various functions.
Therefore, this could make them a more effective solution than metformin, especially when it comes to dementia.
This is an observational study, and as such, no firm conclusions can be drawn about cause and effect.
And the researchers point out that the tracking period, while sufficient for observing dementia outcomes, may not fully capture long-term cognitive effects, especially given the progressive nature of Alzheimer's disease.
They conclude: 'Given the severe societal, familial, and economic burden of diabetes-related dementia, these findings raise important considerations about the role of GLP-1 [receptor agonists] as first-line therapies in [type 2 diabetes] management.
'While further long-term studies are warranted to validate these results, integrating GLP-1 [receptor agonists] as primary therapeutic agents may represent a paradigm shift in preventing the cognitive complications of diabetes.
'Both medications demonstrate neuroprotective properties, such as reducing neuroinflammation and oxidative stress, improving insulin sensitivity, and enhancing cerebrovascular health, which likely contribute to their benefits in overall dementia.'

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