“We think that, by modulating cerebrospinal fluid pressure and reducing intracranial venous sinuses compression, these drugs produce a decrease in the release of calcitonin gene-related peptide (CGRP), a key migraine-promoting peptide”, Dr Braca explained. “That would pose intracranial pressure control as a brand-new, pharmacologically targetable pathway.”
I'm not sure I understand what that means, but I wonder if this would work for people who are not obese?
They are positing that the GLP-1 agonist acts mechanistically to modulate CGRP release. But CGRP involvement in migraine is itself only one potential mechanism that causes migraine. I would like to know whether the subjects who responded to the GLP-1 therapy were also responsive to CGRP monoclonal antibody therapy.
Anecdotes are not data, however I used to have one or more severe migraine headaches weekly. Debilitating migraines. I suffered pretty high blood pressure (which has a very direct relationship with cerebrospinal fluid pressure, which is why I mention this), but aside from that am very healthy and physically fit, exercise regularly, and so on.
I started medication to treat the BP -- telmisartan and amlodipine -- and my BP dropped from 150+/120+ to 115/80. The migraines completely disappeared. I still infrequently get the visual aura that would traditionally precede a migraine, but nothing follows. I haven't had a migraine in the years I've had my BP under control.
Candesartan is actually one of the most used medications for migraine prophylaxis, also for people with normal BP. Your doc might have chosen the med for that reason. Though it's widely used for BP even in people without migraines.
I've had the auras at least since a teenager, but not headaches. Thought is was completely normal, 'til a neurologist said No and that I has having vestibular migraines. Blood pressure was always on the low side of normal.
Family history of migraines and seizures, which some hypothesize have the same root causes. Would be interesting to see GLP-1 tests on epilepsy.
Is there any good consensus on what the deal is with this drug yet? I don't know how to think about GLP-1. In the headlines it seems like every month it's a miracle cure for something new, yet we don't really understand it? But it seems like just generally...everyone, including me, would benefit from being on it...? The whole thing makes me uneasy but I'm not exactly sure why outside of it seems weird to have one drug that is so good at so much.
It’s miracle drug, I’ve been on it for a few years now, it would have been sooner but usage data wasn’t available at the scale I needed before the ozempic craze. I have hEDS and part of that is ME/CFS and uncontrollable weight gain, so naturally I was looking for help with weight loss with the understanding that drugs that help with weight loss could be treating an underlying mechanisms that was causing the weight gain. Low Dose Naltrexone is another drug that also helps with weight loss and hEDS, so I was looking for more of the same. I still don’t know the underlying mechanisms but my autoimmune conditions have largely been resolved. Like cheap solar electricity, I see GLP1s as basically an absolute win. Of course people shouldn’t abuse the drug and they should also change their habits.
Nobody understands why it all helps, they just noticed it does work for something, quickly pushed it to the market first to get patents and get all the profits from it before generics + derivatives hit their pockets. Now, everyone is studying it because there's all new funding coming in for it and finding other versions of it that they can profit off it.
Nobody knows what migraine really is, so this isn't a surprise to them that GLP-1 may help, the main question is; why? So they have another data point proving that gut health has a direct correlation to the brain.
Keep in mind that a lot of the benefits go away once patients come off GLP-1 and we have not seen any studies yet on what happens to people who come off it for long term effects. It may in fact make things even worse and for a lot of people, they may have to stay on it for the rest of their lives.
> [...] quickly pushed it to the market first to get patents and get all the profits [...]
Beyond what others have commented already, especially on obesity and cardiovascular disease, I have to correct this specifically, because it is a very common and honestly understandable misunderstanding people have about these drugs.
While only having appeared in the public consciousness comparatively recently, this class of drugs has been in use for two decades at this stage [0], showcasing a very solid safety profile with well established side-effects [1].
Continued research is important, as is proper prescription and use under the care of a Medical Professional up-to-date on current day evidence based practices (as is the case with all interventions), but to have a proper discussion about these, we shouldn't spread myths such as this being "quickly pushed" out, as these have undergone the clinical trials and regulations established across multiple agencies from multiple governments [2].
Again, it is understandable why these are considered rather new or appeared suddenly, especially if one doesn't take a look into their approval, but I don't see any evidence for them being rushed out or anything of the sort.
> Keep in mind that a lot of the benefits go away once patients come off GLP-1 and we have not seen any studies yet on what happens to people who come off it for long term effects.
Not if they increase muscle mass and change their lifestyle, like every physician (and the FDA/pharma companies) recommend.
> It may in fact make things even worse and for a lot of people, they may have to stay on it for the rest of their lives.
It does not. And some people may.
You know what’s worse than taking a GLP-1 forever? Obesity or metabolic syndrome killing you before you get to “forever.”
It seems weird because we hate finding “bugs” in our bodies, but it happens all the time.
Another example: low dose metformin is largely considered beneficial for most people, at least in a small way. But very few people who aren’t diabetic take it, as the drawback of possible side effects outweighs the potential benefit for someone who doesn’t have symptoms in the first place.
Same thing here. Would it benefit you? Possibly. Do the risks of side effects outweigh that benefit for someone without symptoms? Also possibly.
Yeah... I think part of it is definitely that the profit margin is so high that there's a huge financial incentive to try to make buzz around it before all the patents expire. I guess we'll know for sure when it's available for pennies on the dollar if the buzz continues.
GLP-1 is a naturally occurring hormone regulating blood sugar, satiety, and gastric emptying. Some people simply don't have enough naturally (which can be a result of diet composition and lifestyle -- there are diet and behaviour modifications to increase your natural production) and artificial supplementation is beneficial.
The overwhelming benefits from GLP-1 are courtesy of weight loss and better blood sugar control. Get those two things under control, with or without GLP-1 drugs, and an enormous array of complications are made less likely.
For people with healthy, ideal diets at an optimal weight and with good blood sugar control, there are only remote, hypothetical benefits. There is some evidence it reduces inflammation and might ward off neurodegenerative disorders, but those likely have more of a relationship with blood sugar spikes, and again lifestyle changes are more impactful.
I agree with most of what you are saying but we should also be clear that there some sources of inflammation that are not caused (or fixed) by diet and lifestyle. There is huge upside for some serious chronic conditions that may be helped by GLP-1 but we are still early on in studies for these things.
They are positing that the GLP-1 agonist acts mechanistically to modulate CGRP release. But CGRP involvement in migraine is itself only one potential mechanism that causes migraine. I would like to know whether the subjects who responded to the GLP-1 therapy were also responsive to CGRP monoclonal antibody therapy.
I wonder if the drug itself reduces CGRP or perhaps the altered diet is the cause.
Anecdotes are not data, however I used to have one or more severe migraine headaches weekly. Debilitating migraines. I suffered pretty high blood pressure (which has a very direct relationship with cerebrospinal fluid pressure, which is why I mention this), but aside from that am very healthy and physically fit, exercise regularly, and so on.
I started medication to treat the BP -- telmisartan and amlodipine -- and my BP dropped from 150+/120+ to 115/80. The migraines completely disappeared. I still infrequently get the visual aura that would traditionally precede a migraine, but nothing follows. I haven't had a migraine in the years I've had my BP under control.
Candesartan is actually one of the most used medications for migraine prophylaxis, also for people with normal BP. Your doc might have chosen the med for that reason. Though it's widely used for BP even in people without migraines.
Agree. Candesartan was one of the first line of migraine treatments given to me. Propranalol was the other one. Neither worked in my case.
Interesting to hear as someone who gets the aura thing, but never the migraine pain, and has good blood pressure
I've had the auras at least since a teenager, but not headaches. Thought is was completely normal, 'til a neurologist said No and that I has having vestibular migraines. Blood pressure was always on the low side of normal.
Family history of migraines and seizures, which some hypothesize have the same root causes. Would be interesting to see GLP-1 tests on epilepsy.
Is there any good consensus on what the deal is with this drug yet? I don't know how to think about GLP-1. In the headlines it seems like every month it's a miracle cure for something new, yet we don't really understand it? But it seems like just generally...everyone, including me, would benefit from being on it...? The whole thing makes me uneasy but I'm not exactly sure why outside of it seems weird to have one drug that is so good at so much.
It’s miracle drug, I’ve been on it for a few years now, it would have been sooner but usage data wasn’t available at the scale I needed before the ozempic craze. I have hEDS and part of that is ME/CFS and uncontrollable weight gain, so naturally I was looking for help with weight loss with the understanding that drugs that help with weight loss could be treating an underlying mechanisms that was causing the weight gain. Low Dose Naltrexone is another drug that also helps with weight loss and hEDS, so I was looking for more of the same. I still don’t know the underlying mechanisms but my autoimmune conditions have largely been resolved. Like cheap solar electricity, I see GLP1s as basically an absolute win. Of course people shouldn’t abuse the drug and they should also change their habits.
Nobody understands why it all helps, they just noticed it does work for something, quickly pushed it to the market first to get patents and get all the profits from it before generics + derivatives hit their pockets. Now, everyone is studying it because there's all new funding coming in for it and finding other versions of it that they can profit off it.
Nobody knows what migraine really is, so this isn't a surprise to them that GLP-1 may help, the main question is; why? So they have another data point proving that gut health has a direct correlation to the brain.
Keep in mind that a lot of the benefits go away once patients come off GLP-1 and we have not seen any studies yet on what happens to people who come off it for long term effects. It may in fact make things even worse and for a lot of people, they may have to stay on it for the rest of their lives.
> [...] quickly pushed it to the market first to get patents and get all the profits [...]
Beyond what others have commented already, especially on obesity and cardiovascular disease, I have to correct this specifically, because it is a very common and honestly understandable misunderstanding people have about these drugs.
While only having appeared in the public consciousness comparatively recently, this class of drugs has been in use for two decades at this stage [0], showcasing a very solid safety profile with well established side-effects [1].
Continued research is important, as is proper prescription and use under the care of a Medical Professional up-to-date on current day evidence based practices (as is the case with all interventions), but to have a proper discussion about these, we shouldn't spread myths such as this being "quickly pushed" out, as these have undergone the clinical trials and regulations established across multiple agencies from multiple governments [2].
Again, it is understandable why these are considered rather new or appeared suddenly, especially if one doesn't take a look into their approval, but I don't see any evidence for them being rushed out or anything of the sort.
[0] https://www.ncbi.nlm.nih.gov/books/NBK572151/
[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC5397288/
[2] https://pmc.ncbi.nlm.nih.gov/articles/PMC6667915/
> Keep in mind that a lot of the benefits go away once patients come off GLP-1 and we have not seen any studies yet on what happens to people who come off it for long term effects.
Not if they increase muscle mass and change their lifestyle, like every physician (and the FDA/pharma companies) recommend.
> It may in fact make things even worse and for a lot of people, they may have to stay on it for the rest of their lives.
It does not. And some people may.
You know what’s worse than taking a GLP-1 forever? Obesity or metabolic syndrome killing you before you get to “forever.”
It seems weird because we hate finding “bugs” in our bodies, but it happens all the time.
Another example: low dose metformin is largely considered beneficial for most people, at least in a small way. But very few people who aren’t diabetic take it, as the drawback of possible side effects outweighs the potential benefit for someone who doesn’t have symptoms in the first place.
Same thing here. Would it benefit you? Possibly. Do the risks of side effects outweigh that benefit for someone without symptoms? Also possibly.
Yeah... I think part of it is definitely that the profit margin is so high that there's a huge financial incentive to try to make buzz around it before all the patents expire. I guess we'll know for sure when it's available for pennies on the dollar if the buzz continues.
I agree with you. All I can think is that it's affecting some central mental or physical aspect that has many different outward benefits.
GLP-1 is a naturally occurring hormone regulating blood sugar, satiety, and gastric emptying. Some people simply don't have enough naturally (which can be a result of diet composition and lifestyle -- there are diet and behaviour modifications to increase your natural production) and artificial supplementation is beneficial.
The overwhelming benefits from GLP-1 are courtesy of weight loss and better blood sugar control. Get those two things under control, with or without GLP-1 drugs, and an enormous array of complications are made less likely.
For people with healthy, ideal diets at an optimal weight and with good blood sugar control, there are only remote, hypothetical benefits. There is some evidence it reduces inflammation and might ward off neurodegenerative disorders, but those likely have more of a relationship with blood sugar spikes, and again lifestyle changes are more impactful.
This is absolutely correct. I couldn’t have said it better myself.
(Except I’ll note that’s true for more than one hormone, as tirzepatide is both a GLP1 and GIP agonist, and I believe retatrutide is also Glucagon?)
I agree with most of what you are saying but we should also be clear that there some sources of inflammation that are not caused (or fixed) by diet and lifestyle. There is huge upside for some serious chronic conditions that may be helped by GLP-1 but we are still early on in studies for these things.