7 ms·

From blood sugar to brain relief: GLP-1 therapy slashes migraine frequency

156 points by Anon84 11mo ago

blakesterz 11mo ago
“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?
- llm_nerd 11mo ago
  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.
  - awakeasleep 11mo ago
    Interesting to hear as someone who gets the aura thing, but never the migraine pain, and has good blood pressure
  - znd 11mo ago
    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.
    - RossBencina 11mo ago
      Agree. Candesartan was one of the first line of migraine treatments given to me. Propranalol was the other one. Neither worked in my case.
  - Bloating 11mo ago
    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.
- RossBencina 11mo ago
  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.
  - cheald 11mo ago
    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-cortical-depression 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.
- francisofascii 11mo ago
  I wonder if the drug itself reduces CGRP or perhaps the altered diet is the cause.
  - apple4ever 11mo ago
    I was wondering the same thing. Might be a mix depending on person.
neom 11mo ago
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.
- michaelbuckbee 11mo ago
  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.
  - toomuchtodo 11mo ago
    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 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)
- llm_nerd 11mo ago
  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.
fudged71 11mo ago
Is there a centralized tracker for all these off-label benefits of GLP-1? Besides meta-reviews and one-off Deep Research reports
jodje 11mo ago
how is 26 people statistically relevant??
- ender341341 11mo ago
  It's relevant in that it's enough to cause them to plan to do a bigger study so we can say with more clarity how if it actually helps.
- arjie 11mo ago
  Well, that depends on the effect size etc. right? There's a chocolate bar in front of you and your two buddies. You split it in thirds. As soon as one of your buddies eats his, he drops dead. Your other buddy says "Sample size of 1. Psh. Billions have eaten chocolate.". He eats his. Drops dead. The sample size is now 2. You eat yours or not? If the answer is yes, well all right. If the answer is no, weaken the effects until you see what crosses the threshold of "should we study this more?".
jodje 11mo ago
how is 26 people statistically relevant???
PKop 11mo ago
Obesity is associated with increased rate of migraine, so their symptoms could have gone away by virtue of losing weight. Let's see what it does for non obese.
- gbalint 11mo ago
  The article specifically mentions that the weight loss was not enough to explain the effect on the migraine: "Importantly, while participants’ body mass index declined slightly (from 34.01 to 33.65), this change was not statistically significant. An analysis of covariance confirmed that BMI reduction had no effect on headache frequency, strengthening the hypothesis that pressure modulation, not weight loss, drives the benefit."
- Tarsul 11mo ago
  When I developed pre-diabetes symptoms (having to drink a lot - like 5-6l per day, consequently having to pee a lot, when not doing the first: getting headaches), I noticed that cutting on sugar meant (next to other benefits) that the thirst-induced headaches were the first thing that went away. Not the thirst itself (still have it). However, not an expert on headaches and can't say if it has anything to do with the migraines in the article. But the point that reducing sugar helps in a myriad of ways, stands and is worth repeating.
Night_Thastus 11mo ago
Oh man, I'd love for a reduction in that. I sort-of deal with it. As a kid I had nearly daily migraines - go into a very dark quiet room and be happy when I fell asleep, since I knew the migraine wouldn't be there when I woke up. These days it's just headaches, 99% sure it's muscle tension in my neck. Kinda doubt GLP-1 could do anything for that, but I'd be pleasantly surprised....
- asciimov 11mo ago
  Get your magnesium level checked. Those that suffer from chronic migraines often are deficient in magnesium and will see a significant reduction in events after 4-6 weeks on a daily Magnesium supplement.
- totallykvothe 11mo ago
  I had very similar issues, both as a kid and an adult. I now take 500mg of Magnesium (Malate or Glycinate. NOT Citrate, as that is a laxative) nearly every night, and my headaches are almost completely gone now. I still get one every once in a while, but it's infrequent enough that I no longer worry about my use of Ibuprofen to manage it.
frankest 11mo ago
These medicines reduce the cravings for sugar. Is it possible that all of these beneficial side effects are just benefits from not abusing sugar.
- kion 11mo ago
  retaglutide is the next gen (3rd) GLP-1 which is in phase 3 trials now. It is a triple antagonist (current are dual GLP-1/GIP). It adds glucagon, and apparently that comes with not only greatly increased weightloss, but also wicked sugar cravings. These things do way way more than just appetite and craving suppression.
  - fragmede 11mo ago
    Interesting! how does that work though? I thought reduced sugar craving was part of how GLP-1s aid in weight loss as the paitent craves sugar less and thus eats less.
    - kion 11mo ago
      I'm not a biochemist, so I can't say with any authority, but presumably its to do with the 3rd antagonist and its impact on glucagon. Most of what I have heard is through Reddit communities for the on-market drugs (1st and 2nd gen peptides). The anecdotes from Retatrutide sound like it has way less impact on appetite and for some people that's actually a downside even though the weight loss effects appears to be significantly more powerful.
throwaway2037 11mo ago
I cannot believe this (related) article from 2024 never got posted to HN: (I just posted it now) Why Does Ozempic Cure All Diseases? https://www.astralcodexten.com/p/why-does-ozempic-cure-all-diseases https://www.astralcodexten.com/p/why-does-ozempic-cure-all-d... I highly recommend it.
ThinkBeat 11mo ago
I know several people who struggle with migraines carry tablets of grape sugar and if taken early they do say it helps a lot. (Note: FOR SOME, not all, probably a small minority could be all)
kouunji 11mo ago
My partner suffers from migraines and also suffered a traumatic brain injury in a car accident. I got her to try glp-1 based on some of the research I’d been reading…and it has been an absolute game changer.
egberts1 11mo ago
Surely some enterprising prediabetic individuals can experiment on these drugs with Bluetooth-glucose monitoring devices. Anecdotal evidence, anyone? For me, prechewing pasta thoroughly knocked off 12-16 from my glucose level. (Converting carbs to dextrose in the mouth?).

156 points by Anon84 11mo ago

“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?

llm_nerd 11mo ago
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.
- awakeasleep 11mo ago
  Interesting to hear as someone who gets the aura thing, but never the migraine pain, and has good blood pressure
- znd 11mo ago
  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.
  - RossBencina 11mo ago
    Agree. Candesartan was one of the first line of migraine treatments given to me. Propranalol was the other one. Neither worked in my case.
- Bloating 11mo ago
  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.
RossBencina 11mo ago
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.
- cheald 11mo ago
  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-cortical-depression 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.
francisofascii 11mo ago
I wonder if the drug itself reduces CGRP or perhaps the altered diet is the cause.
- apple4ever 11mo ago
  I was wondering the same thing. Might be a mix depending on person.

neom 11mo ago

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.

michaelbuckbee 11mo ago
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.
- toomuchtodo 11mo ago
  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 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)
llm_nerd 11mo ago
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.

fudged71 11mo ago

Is there a centralized tracker for all these off-label benefits of GLP-1? Besides meta-reviews and one-off Deep Research reports

jodje 11mo ago

how is 26 people statistically relevant??

ender341341 11mo ago
It's relevant in that it's enough to cause them to plan to do a bigger study so we can say with more clarity how if it actually helps.
arjie 11mo ago
Well, that depends on the effect size etc. right? There's a chocolate bar in front of you and your two buddies. You split it in thirds. As soon as one of your buddies eats his, he drops dead. Your other buddy says "Sample size of 1. Psh. Billions have eaten chocolate.". He eats his. Drops dead. The sample size is now 2. You eat yours or not? If the answer is yes, well all right. If the answer is no, weaken the effects until you see what crosses the threshold of "should we study this more?".

jodje 11mo ago

how is 26 people statistically relevant???

PKop 11mo ago

Obesity is associated with increased rate of migraine, so their symptoms could have gone away by virtue of losing weight. Let's see what it does for non obese.

gbalint 11mo ago
The article specifically mentions that the weight loss was not enough to explain the effect on the migraine: "Importantly, while participants’ body mass index declined slightly (from 34.01 to 33.65), this change was not statistically significant. An analysis of covariance confirmed that BMI reduction had no effect on headache frequency, strengthening the hypothesis that pressure modulation, not weight loss, drives the benefit."
Tarsul 11mo ago
When I developed pre-diabetes symptoms (having to drink a lot - like 5-6l per day, consequently having to pee a lot, when not doing the first: getting headaches), I noticed that cutting on sugar meant (next to other benefits) that the thirst-induced headaches were the first thing that went away. Not the thirst itself (still have it). However, not an expert on headaches and can't say if it has anything to do with the migraines in the article. But the point that reducing sugar helps in a myriad of ways, stands and is worth repeating.

Night_Thastus 11mo ago

Oh man, I'd love for a reduction in that. I sort-of deal with it. As a kid I had nearly daily migraines - go into a very dark quiet room and be happy when I fell asleep, since I knew the migraine wouldn't be there when I woke up. These days it's just headaches, 99% sure it's muscle tension in my neck. Kinda doubt GLP-1 could do anything for that, but I'd be pleasantly surprised....

asciimov 11mo ago
Get your magnesium level checked. Those that suffer from chronic migraines often are deficient in magnesium and will see a significant reduction in events after 4-6 weeks on a daily Magnesium supplement.
totallykvothe 11mo ago
I had very similar issues, both as a kid and an adult. I now take 500mg of Magnesium (Malate or Glycinate. NOT Citrate, as that is a laxative) nearly every night, and my headaches are almost completely gone now. I still get one every once in a while, but it's infrequent enough that I no longer worry about my use of Ibuprofen to manage it.

frankest 11mo ago

These medicines reduce the cravings for sugar. Is it possible that all of these beneficial side effects are just benefits from not abusing sugar.

kion 11mo ago
retaglutide is the next gen (3rd) GLP-1 which is in phase 3 trials now. It is a triple antagonist (current are dual GLP-1/GIP). It adds glucagon, and apparently that comes with not only greatly increased weightloss, but also wicked sugar cravings. These things do way way more than just appetite and craving suppression.
- fragmede 11mo ago
  Interesting! how does that work though? I thought reduced sugar craving was part of how GLP-1s aid in weight loss as the paitent craves sugar less and thus eats less.
  - kion 11mo ago
    I'm not a biochemist, so I can't say with any authority, but presumably its to do with the 3rd antagonist and its impact on glucagon. Most of what I have heard is through Reddit communities for the on-market drugs (1st and 2nd gen peptides). The anecdotes from Retatrutide sound like it has way less impact on appetite and for some people that's actually a downside even though the weight loss effects appears to be significantly more powerful.

throwaway2037 11mo ago

I cannot believe this (related) article from 2024 never got posted to HN: (I just posted it now) Why Does Ozempic Cure All Diseases? https://www.astralcodexten.com/p/why-does-ozempic-cure-all-diseases https://www.astralcodexten.com/p/why-does-ozempic-cure-all-d... I highly recommend it.

ThinkBeat 11mo ago

I know several people who struggle with migraines carry tablets of grape sugar and if taken early they do say it helps a lot. (Note: FOR SOME, not all, probably a small minority could be all)

kouunji 11mo ago

My partner suffers from migraines and also suffered a traumatic brain injury in a car accident. I got her to try glp-1 based on some of the research I’d been reading…and it has been an absolute game changer.

egberts1 11mo ago

Surely some enterprising prediabetic individuals can experiment on these drugs with Bluetooth-glucose monitoring devices. Anecdotal evidence, anyone? For me, prechewing pasta thoroughly knocked off 12-16 from my glucose level. (Converting carbs to dextrose in the mouth?).