[HN Gopher] From blood sugar to brain relief: GLP-1 therapy slas...
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From blood sugar to brain relief: GLP-1 therapy slashes migraine
frequency
Author : Anon84
Score : 113 points
Date : 2025-11-26 15:49 UTC (7 hours ago)
(HTM) web link (www.medlink.com)
(TXT) w3m dump (www.medlink.com)
| blakesterz wrote:
| "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 wrote:
| 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 wrote:
| Interesting to hear as someone who gets the aura thing, but
| never the migraine pain, and has good blood pressure
| znd wrote:
| 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 wrote:
| 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 wrote:
| 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 wrote:
| 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 wrote:
| 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/s
| preading-...)
|
| 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 wrote:
| I wonder if the drug itself reduces CGRP or perhaps the altered
| diet is the cause.
| neom wrote:
| 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 wrote:
| 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 wrote:
| 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)
| llm_nerd wrote:
| 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.
| borski wrote:
| 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?)
| barrenko wrote:
| "Incretins" is the keyword here.
| borski wrote:
| Indeed! Thank you!
| snarf21 wrote:
| 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.
| mikhailt wrote:
| 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.
| borski wrote:
| > 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."
| Topfi wrote:
| > [...] 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/
| throwawaysleep wrote:
| > 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.
| redwall_hp wrote:
| Oh no, my psoriasis will come back if I stop taking my
| psoriasis biologic. Oh wait, why the fuck would I want to
| do that?
| aetherson wrote:
| Do you know what else stops working if you stop taking the
| therapy?
|
| Diet and exercise.
| inglor_cz wrote:
| Benefits of reading, swimming, walking, playing an instrument
| etc. will go away too if you stop doing that thing.
|
| Biology rarely awards something "forever". Maybe one day we
| can "fix" obese metabolisms permanently by killing off some
| receptors etc., but in that case, I would be afraid of
| intractable long-term effects even more.
| borski wrote:
| 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.
| pfdietz wrote:
| Metformin's side effects are pretty minor, I find. So don't
| let that possibility stop you if you think you could benefit.
| borski wrote:
| I agree with you. My point was simply that most physicians
| only prescribe if the potential benefits are obvious and
| outweigh the potential risks / side effects. Doing nothing
| is something better than doing something without an obvious
| benefit.
|
| If you're obese, have metabolic syndrome, have T2D, or any
| other number of issues that we've seen GLP-1s (or
| metformin) help with - then the medications can be a
| godsend.
| zug_zug wrote:
| 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.
| cjbgkagh wrote:
| 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.
| throwfish3000 wrote:
| Does having uncontrollable weight gain help you get jacked?
| Being jacked and fat is tons of fun, better than being
| skinny.
| cjbgkagh wrote:
| No, it's the worst, just fat but also because I was dieting
| so much I couldn't tell if I was tired from not eating
| enough or if I had ME/CFS. After I gained the weight people
| would blame my fatigue on me being fat, ignoring that I was
| fatigued before gaining the weight.
| mattgreenrocks wrote:
| GLP-1s seem to induce/mimic gastroparesis, which also can
| occur with hEDS. Has that been an issue? Also, do you have
| MCAS?
|
| (Also have hEDS.)
| cjbgkagh wrote:
| Yeah, that's one of the reasons I waited for usage data is
| that I was pretty sure people with hEDS would have an
| overly strong reaction, and that did happen in my case and
| appears to have happened with other with hEDS. I started at
| 0.025mg (1/20th the 0.5mg starting dose at the time) and
| still got temporary gastroparesis which was indeed very
| uncomfortable. I had done long term fasting prior to
| semaglutide so I had to just stop eating for a long time
| while the effects started to wear off. Over the first year
| I ramped up linearly to 1mg and I've been at that dose
| since.
| mattgreenrocks wrote:
| Wow. Glad it panned out for you.
| asafira wrote:
| 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.
| bigiain wrote:
| > but I suspect an LLM can hallucinate several more examples.
|
| FTFY
|
| (great comment otherwise)
| bparsons wrote:
| 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.
| tracker1 wrote:
| 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.
| mikaraento wrote:
| I'm sorry you went through that
| basisword wrote:
| Curious how you tied the side effects to GLP-1 when they
| didn't appear for a year and took so long to go away after
| stopping? Is it possible it was unrelated?
| doctoboggan wrote:
| 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.
| johnfn wrote:
| One reported benefit from Ozempic is that it improves self
| control. For instance, there are some studies that show it's
| easier to stop smoking on Ozempic[1]. I can't think of any
| way that would be modulated just by being less overweight.
|
| [1]:
| https://www.goodrx.com/classes/glp-1-agonists/semaglutide-
| fo...
| testing22321 wrote:
| Once you have proven to yourself you can eat less and lose
| weight, you believe you can do the same with other things
| like smoking.
|
| Makes sense
| barrenko wrote:
| That's not how it works.
| sheepdog wrote:
| Correct. Reduced smoking, alcohol, and other behaviors have
| been documented. There's a complex relationship between the
| gut and certain behaviors. These drugs slow down gut
| processing, and delay the reward mechanism. With slightly
| less reward from the body, the scales may tip slightly in
| favor of self control.
|
| Source: currently using GLP and seeing reduced positive
| feedback from alcohol (incidentally)...
| yieldcrv wrote:
| so its a cure for the body positivity movement and all of the
| proponents reverted back to default understanding of health
| renewiltord wrote:
| It's just that when something is widespread enough you can
| actually study other effects it has. Sort of like how
| psilocybin and weed had all these other effects but we couldn't
| study them till they got a little less criminalized. All sorts
| of shit does stuff, but we grandfathered in substances and
| froze everything for a while. Then COVID came along and a bunch
| of people started doing telemedicine and before you know it
| compounding pharmacies were handing out GLP-1RAs as a
| substitute for the phentermine they were passing out. Not
| scheduled, absolutely effective, great stuff.
|
| Then with all that use in the wild you could rock and roll.
| Only problem is that off-label use like me with my retatrutide
| makes some population studies less effective than before.
| ascorbic wrote:
| There are currently several hypotheses. Some say that it's just
| because it helps you lose weight, and obesity increases the
| risk of so many things. However while this is true, there are
| lots of examples where there are effects even when you control
| for weight loss. One of the more interesting theories is that
| it's down to their anti-inflammatory effects, because chronic
| inflammation is linked to so many conditions.
| jorvi wrote:
| The Alzheimer """cure""" claim was already disproven by another
| study. Aside from that, the people who stop taking GLP, 75%
| gain 50-75% of their bodyweight back and lose all concomitant
| cardiovascular, cancer etc. risk benefits.
|
| No research out on, say, alcoholism yet, but I'd hazard a guess
| the results are the same.
|
| This is not a cravings loss drug but largely a cravings
| management drug. Which is still pretty great but it saddles
| healthcare funding systems with an enormous burden for the next
| 20 years. Or you keep it private, which means you introduce an
| enormous gulf of health inequality.
|
| I hate that our solution to obesity is not the way Iceland
| treated it's youth drinking problem: reduce access to the
| harmful thing, give people money and support to do the healthy
| thing. Stick with it instead of cancelling the program if it
| doesn't show results in 4 years.
|
| Modern food (started in the 80s) has carefully been engineered
| to be as addictive as possible, health consequences be damned.
| Let's start fixing the problem there.
| leoh wrote:
| Effects on Alzheimer's have not been disproven; it was shown
| that there wasn't a perceivable benefit from oral semaglutide
| at the doses prescribed for folks with a certain degree of
| progression of the disease.
| SubiculumCode wrote:
| It should be treated like other important drugs. The U.S.
| buys the patent (or other variant) letting it become generic
| philipkglass wrote:
| _This is not a cravings loss drug but largely a cravings
| management drug. Which is still pretty great but it saddles
| healthcare funding systems with an enormous burden for the
| next 20 years._
|
| Semaglutide goes off-patent in 2032 in the US, and in 2026 in
| Canada and China:
|
| https://journals.library.columbia.edu/index.php/stlr/blog/vi.
| ..
|
| https://www.ncbi.nlm.nih.gov/books/NBK602920/table/t03/
| jorvi wrote:
| Wait, what? I thought these were extremely new drugs, only
| approved for a couple of years now.
| mise_en_place wrote:
| It's Gila monster venom. You may become a druid while taking
| it.
| m463 wrote:
| Reminds me of aspirin. It started from willow tree bark
| thousands of years ago. I'm pretty sure it was not understood
| for most of that time either.
|
| I wonder when the first person understood how it worked. (if
| anyone understands it now?)
| didibus wrote:
| It's too soon to really know the downsides. Statins for example
| only recently are better understood and there's a lot more
| downsides we know about now.
|
| It's likely going to be true for GLP-1 as well.
| fudged71 wrote:
| Is there a centralized tracker for all these off-label benefits
| of GLP-1? Besides meta-reviews and one-off Deep Research reports
| jodje wrote:
| how is 26 people statistically relevant??
| ender341341 wrote:
| 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 wrote:
| 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 wrote:
| how is 26 people statistically relevant???
| PKop wrote:
| 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 wrote:
| 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 wrote:
| 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 wrote:
| 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 wrote:
| 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.
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