Is there a centralized tracker for all these off-label benefits of GLP-1? Besides meta-reviews and one-off Deep Research reports
From blood sugar to brain relief: GLP-1 therapy slashes migraine frequency
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Re: From blood sugar to brain relief: GLP-1 therapy slashes migraine frequency
#22“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 th…
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.
My wife has chronic migraines which are successfully mitigated by rimegepant (gepants are CGRP antagonists), and didn't have any particular change in headaches from GLP-1.
What has helped, interestingly, is supplemented creatine HCl (she went with hcl because it's absorbed substantially faster than monohydrate). We've learned that depletion of neural ATP levels can result in an energy crisis which results in cortical spreading depression, which stimulates the release of CGRP. (https://www.sciencedirect.com/topics/neuroscience/spreading-...)
She's found that a) daily supplementation of creatine has reduced her headache days, and b) an immediate dose of creatine upon onset of a headache frequently aborts or mitigates it. Her need for the gepants has dropped to a tiny fraction of what it was prior to starting creatine.
She's tried everything under the sun, had all the scans, tried all the meds and procedures, and creatine and gepants are the only things she's found that have worked. She's not a placebo responder, and hasn't responded to about a zillion other therapies, so we're pretty sure it's not just placebo effect.
Re: From blood sugar to brain relief: GLP-1 therapy slashes migraine frequency
#23Is 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 dru…
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.
It patches the reward center in the brain, which improves everything downstream of that (as mentioned in llm_nerd's sibling comment to yours).
https://news.ycombinator.com/item?id=45907422 (citations)
(i am hopefully that probiotics might be a future path to curating gut microbiota that meets an individual's GLP-1 in vivo production needs based on target metabolic outcome, but immediate intervention is welcome for obvious health reasons at scale)
Re: From blood sugar to brain relief: GLP-1 therapy slashes migraine frequency
#24Is 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 dru…
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 ga…
Does having uncontrollable weight gain help you get jacked? Being jacked and fat is tons of fun, better than being skinny.
Re: From blood sugar to brain relief: GLP-1 therapy slashes migraine frequency
#25Is 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 dru…
There is large-enough consensus on this drug for its main use cases (treating diabetes and obesity), but more importantly for this conversation: it's actually quite common for drugs to get new indications after their initial one --- at which point, there might be a new, broader consensus on what the drug is good for.
Clinical trials are designed to treat a very specific subclass of individuals; pharmaceutical companies very carefully choose that subclass in an attempt to help ensure the clinical trials are successful, which is a combination of the following:
- Positive, statistically-significant results. - FDA approval with those results. - Insurance companies willing to pay for the given treatment. - A decent-sized addressable market.
Examples of drugs/medical technologies later getting other indications: - Minoxidil was a drug that only later got its approval to be used as a hair loss treatment; there are currently clinical trials for a more "advanced" minoxidil oral pill for this use case. - Re: GLP-1s: Tirzepatide later got an indication that it effectively treats sleep apnea. There are very many other clinical trials ongoing for GLP-1s, but perhaps most recently, Semaglutide (ozempic) failed to show statistical significance as a treatment for Alzheimer's. - The Galleri blood screening/test. The initial indication they are going for is folk who are at highest risk for cancer (I believe that's individuals between the ages of 50 and 70); however, that's not to say it would be bad for individuals younger or older. But, this is a way to help ensure the earliest product has a successful outcome.
These are ones I know off the top of my head, but I suspect an LLM can give several more examples.
Re: From blood sugar to brain relief: GLP-1 therapy slashes migraine frequency
#26Is 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 dru…
There is a growing body of evidence that this is the most significant class of drugs since the introduction of statins. Whatever it is doing, it is delivering tens of millions of quality adjusted life years.
Re: From blood sugar to brain relief: GLP-1 therapy slashes migraine frequency
#27Is 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 dru…
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…
> Keep in mind that a lot of the benefits go away once patients come off GLP-1
All medicines taken for chronic conditions as this way.
Re: From blood sugar to brain relief: GLP-1 therapy slashes migraine frequency
#28Is 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 dru…
All I know is I had some miserable side effects that started after a couple years that just progressively got worse while on them... when I found out it was the Trulicity/Ozempic I stopped, and the effects coming off were nearly as miserable... took almost a year to recover coming off and still dealing with the fallout.
Re: From blood sugar to brain relief: GLP-1 therapy slashes migraine frequency
#29Is 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 dru…
I had just assumed that all these new things this is a cure for are just down stream affects of being overweight, and losing the weight also reduces the incidence of these other issues as well.
Re: From blood sugar to brain relief: GLP-1 therapy slashes migraine frequency
#30Is 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 dru…
There is large-enough consensus on this drug for its main use cases (treating diabetes and obesity), but more importantly for this conversation: it's actually quite common for drugs to get new indications after their initial one --- at which point, there might be a new, broader consensus on what the drug is good for. Clinical trials are designed to treat a very specific subclass of individuals; pharmaceutical compani…
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