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New evidence brings more good news about the unanticipated effects of the GLP-1 receptor agonists. https://www.medscape.com/viewarticle/glp-1-drugs-might-cut-dementia-risk-half-2025a10008bs?src=soc_yt -- TRANSCRIPT -- Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr F. Perry Wilson from the Yale School of Medicine. It’s quite a thing that we live in an era with the biggest blockbuster weight-loss drugs in history, and I can look at you straight-faced and say, yeah, but honestly that’s not the most interesting thing about the GLP-1 receptor agonists such as Ozempic. Beyond their clear utility in weight loss, we have good data that demonstrate the drugs lead to improvements in rates of heart disease, liver disease, and even all-cause mortality, and intriguing reports of strange off-target effects: a reduction in gambling, drinking, drug use, smoking, and compulsive shopping. It’s honestly hard to find an organ system or self-destructive behavior that GLP-1 drugs don’t seem to improve somehow. It’s almost strange. It’s as if the statins came out and everyone was excited about the cholesterol going down, and then we discovered that they reversed hair loss or took three strokes off your golf game. How does one drug do so many things? I think the behavioral changes are the clue. The fact that people may drink or smoke less on these drugs should tell you that something is happening in their brains. And if these drugs are acting on the brain, you might well wonder if they can reduce the risk for brain disease — dementia. And, at least according to a new study, the answer appears to be yes. As the GLP-1 drugs started getting more and more popular, I decided to perform some due diligence and refresh what I had learned in med school about this thing called “glucagon-like peptide.” These drugs bind to the same receptor that GLP does, primarily to cause the pancreas to release more insulin when blood sugar is high. But we have plenty of drugs that stimulate insulin release. And they don’t seem to have all these other weird effects. So, what’s going on? When a drug acts on a specific receptor, it is worth seeing what cells in the body have that receptor, and this is a pretty interesting figure that shows that. You see high expression in the pancreas — no surprise. But next is expression in the heart muscle — interesting, considering these drugs have been shown to reduce the risk for heart disease. Then the salivary glands, and then… the cerebral cortex. The brain. And not just any part of the brain, the thinking part of the brain. A lot happens when these drugs bind to a receptor on a cell. But the brain is a mysterious and important organ. In contrast, the heart is relatively simple, and there are multiple randomized trials that show that GLP-1 drugs, as well as some other drugs for diabetes, such as the SGLT2 inhibitors, pioglitazone, and metformin, reduce the risk for cardiovascular disease in people with diabetes. So, it makes sense to ask whether these drugs would do the same for brain disease. Enter this study, "Cardioprotective Glucose-Lowering Agents and Dementia Risk," from Catriona Reddin and colleagues in JAMA Neurology. It’s an impressive bit of work combining data from 23 different randomized trials of these drugs including more than 150,000 individual people, to determine whether they reduce the risk for dementia. This is the best evidence we have to date for a neuroprotective effect of GLP-1 inhibitors. And this is the only type of study that could give us this evidence. The reason you need to combine so much data to detect a signal is that, to date, no randomized trials of GLP-1 drugs have been designed with dementia as a primary outcome. Transcript in its entirety can be found by clicking here: https://www.medscape.com/viewarticle/glp-1-drugs-might-cut-dementia-risk-half-2025a10008bs?src=soc_yt

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