We’re bringing you everything you need to know about the latest updates on GLP-1 medications, straight from a credited scientist with numerous awards for his groundbreaking work on glucagon-like peptide-1 (GLP-1) – Daniel Drucker.

Ready? Let’s go!

Here’s what, Daniel Drucker, who has been researching GLP-1 for decades, has to say about this family of medications.

GLP-1 agonists were approved for treating obesity back in 2014, so it’s been 10 years since liraglutide hit the market. But why didn’t it catch the public’s attention until recently?

Early experiments focused on demonstrating insulin secretion, and patents were led for using GLP-1 in diabetes treatment. The story around food intake and weight loss developed more gradually and took longer to unfold.

Why Did It Take So Long to Get to Obesity?

GLP-1 agonists have really taken o in the last three or four years. Novo Nordisk initially looked at liraglutide doses for diabetes, which was 1.8 milligrams once daily for people with type 2 diabetes. They then aimed to boost the dose to 3 milligrams once a day for better weight loss results. Learning from this, they introduced Semaglutide for type 2 diabetes with doses of 0.5 and 1 milligram.

They kept experimenting with the same question, what if we increased the dose even more? They landed on 2.4 milligrams once a week, and that’s when we started to see the spectacular weight loss results, we’re now familiar with.

The organs

There are many di places in the body where you don’t see a lot of GLP-1. In the heart, blood vessels, the liver, in many organs where you don’t see a lot of GLP-1 receptors, and you don’t see a lot of GLP-1 receptors on immune cells. So, this really leads us to the question, how does it act on all these organs where we don’t see enough or any GLP-1 receptors?

Well, this is exactly why scientists are so focused on the brain when studying GLP-1.

Getting to the brain

You may be familiar with the fact that our nervous system can communicate with many different cell types in almost every organ and that GLP-1 is naturally made in the brain and the gut, but it doesn’t last long given it’s a protein.

This raises the question when one gets these GLP-1 agonist medication, how do they reach the brain? Isn’t there a barrier that stops many things from getting into the brain?

Daniel D. answered this important question by explaining: GLP-1 agonists don’t get into the brain very well. There’s a lot of data on this. People have done experiments using radioactive or unresent markers to see how much gets past the blood-brain barrier, and it turns out, that not much does.

The best way to explain it is that GLP-1 can send messages to the brain, but it doesn’t directly enter the brain. In other words, it does reach some of the accessible neurons that have GLP-1 receptors, and they probably transmit signals deeper into the brain and then activate signal transduction.

One way to look at it is if you use c-fos, the protein, which is an immediate early gene, which is increased when we activate neurons, we see rapid activation of c-fos in many regions that are deep within the brain within minutes.

It is found that GLP-1 is not getting directly to those neurons, but it’s activating pathways that turn on those neurons. And so, there’s probably a very intricate set of pathways that sense the GLP-1 and the accessible neurons and then transmit those signals deeper into the brain.

This is especially interesting when we consider using GLP-1 for neurodegenerative diseases like Parkinson’s and Alzheimer’s.

Would it be more effective if we could get more of the agonist into the brain, or would that just lead to more side effects? This is a really important area for study being looked at beyond diabetes and obesity.

Inflammation

It was noticed that neurons that expressed the GLP-1 receptor, which when blocked or abrogated eliminated the ability of GLP-1 to reduce in inflammation in the periphery in white cells or lungs. So, it’s been known for some time that the brain can control the immune system.

GLP-1 agonists exert an anti-inflammatory ect throughout many different mechanisms, this has a very significant implication for our overall health, particularly in conditions categorized by chronic in inflammation such as obesity, diabetes, and even neurodegenerative diseases.

So how does GLP-1 agonist produce their anti-in inflammatory ect and the potential benefits associated with these actions?

First off, let’s begin with the modulation of immune responses. GLP-1 has an important role in controlling the activity of the immune cells involved in in inflammation, it can dampen the response of immune cells called macrophages. These cells are key players in the in inflammatory process. They reduce the production of pro-inflammatory molecules, and instead, they promote the release of anti-in inflammatory substances.

You might be thinking “Okay but how does GLP-1 exert anti-in inflammatory ects?” This leads to the second salient part: the Inhibition of Inflammatory Pathways.

These are the signaling pathways that GLP-1 interferes with to disrupt from causing in inflammation. For instance, GLP-1 can stop the activation of nuclear factor-kappa B (NF-κB), which is a key player in in inflammation that turns on genes causing in inflammation. By blocking NF-κB and other similar pathways, GLP-1 reduces the production of in inflammatory substances like tumor necrosis factor-alpha.

And so, this is just the latest piece in the puzzle of how GLP-1 might reduce in inflammation.

Conclusion

The future of GLP-1 agonists looks incredibly promising. These drugs, while not directly penetrating the brain, engage with it in complex ways that lead to significant health benefits. From their established role in managing obesity and diabetes to emerging evidence of their e ects on cardiovascular health and neurodegenerative diseases.

GLP-1 agonists are shaping up to be a game-changer in modern medicine.

The potential of these medications extends beyond their current applications. Research is revealing even more about their ability to mitigate in inflammation, improve mental clarity, and possibly neurodegenerative diseases. As we continue to explore their full range of benefits, GLP-1 agonists could become a cornerstone in transformative advancements that could rede ne how we approach chronic conditions and overall wellness.