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.
>pharmaceutical companies very carefully choose that subclass in an attempt to help ensure the clinical trials are successful
You mean that they mainly choose middle class white males with degrees? It's not some racism, it's just an observation (which one may call a clinical meta-study of a sort), that this is the group that follows doctor's advice best of all thus making results the least noisy. Which in turns makes trials many times cheaper because doing otherwise would have required much larger patient groups to compensate for higher noise.
Going beyond that will be many *-isms at once, but google it up.
This is a major factor impacting quality of drugs. For instance, GLP-1 itself should be probably prescribed to Blacks starting with lower threshold BMI because they appear to benefit more from it in 27-30 BMI range, and are more susceptible to weight-related health issues than whites in these "overweight" ranges, and more likely to develop diabetes from it, and overall. Doing so would have increased overall society's benefits from GLP-1 a lot. But no one knows for sure because clinical trials almost didn't include them.
FTFY
(great comment otherwise)
(Also have hEDS.)
It's conceivable that future drug discoveries could safely reduce the amount of lifting required. But the protein requirements will always remain.
These are very new and untested in large populations, but from everything I've heard so far it seems they still won't magically make you gain muscle without lifting heavy things and eating protein. They'll just take the limiter off when you do that so you can gain even more muscle than you would otherwise.
This is my guess as well. It's been eye opening correlating on/off GLP-1s, wearing a CGM (blood glucose monitor), and seeing how that data changes depending on what I eat and how that further impacts what I eat an hour or three later.
Tightly controlled blood sugar was life changing to me - and I wasn't diabetic or at risk to become so.
[1]: https://www.goodrx.com/classes/glp-1-agonists/semaglutide-fo...
Source: currently using GLP and seeing reduced positive feedback from alcohol (incidentally)...
Makes sense
It could absolutely be a factor in the effectiveness.
Placebo is a highly effective drug.
I say this as an extreme evangelist of GLP-1s. Behavior modification and habit building appears to me to be a large part of it. Friends on it who have used to as a performance enhancing drug to change habits have generally stuck with newly developed habits even coming off the drug. Friends who used it as a magic weight loss drug largely returned to previous weights and poor health, even some maxing out the doses over time.
It's frustrating because if this combination of things doesn't line up, being busy so that I skip a workout and then drink a glass of wine to relax in the evening would be totally fine. But add a couple more variables that are out of my control, then a migraine will hit me and I can't do anything for two days.
I can see that a drug which reduced my craving for things like chocolate, coffee, wine, food - especially at times when I'm stressed and my willpower is low - might have large results on reducing my migraines.
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.
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.
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.
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/
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.”
Bingo. Being obese has so many downstream effects. Anything that helps that is tremendous.
All medicines taken for chronic conditions as this way.
The idea that drugs shouldn't be taken forever just doesn't make any sense. There are plenty of forever diseases, naturally those should require forever drugs.
Diet and exercise.
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.
Plenty of people take regular doses of caffeine for their entire lives and we don't moralize at them about it.
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)
I wonder when the first person understood how it worked. (if anyone understands it now?)
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.
(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?)
Yes, inflammation is a thing in the medical world. There are actual tests to measure it. Having higher levels is generally considered a negative indicator.
It's likely going to be true for GLP-1 as well.
Google AI tells me:
> The main downsides of statins include muscle pain, weakness, and fatigue, and a small increased risk of developing type 2 diabetes.
Either that or out-of-touch fitness people who push overly restrictive diets and workout plans. Which work, but actually no they don't, because nobody with a sane mind would want to stick to them. And now you're back at square one but you also have a disdain for food and exercise.
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.
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.
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...
I don't think that framing is right, from another study:
* 17.5% maintained 75+% of their weight loss
* 25% maintained 50-75% of their weight loss
* 23% maintained 25-50% of their weight loss
* 24% maintained 0-25% of their weight loss
At least 75% (possibly more!) maintained some form of weight loss 25% to 75%+. That is tremendous. And 43% maintained 50%+! For reducing being overweight, that is just amazing.
> 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.
I don't think it's possible to "reduce access to the harmful thing" when that thing is "food".
Many people show long term results even stopping it. I don't understand this desire to say "people should suffer!" instead of taking something that helped them.
Plenty of people have tried (me included) but if it was easy to lose weight, nobody would be long term overweight.
A person cannot lose weight that fast normally, losing 70 or 100 pounds at 2-4 pounds a month is alot of time. But I was able to lose it and go from not being able to run, to being able to walk and run all day at festivals. Guess how it's easier to lose weight now...
I think alot of people don't understand how hard it is to exercise or lose weight while fat, just due to the join pain and muscles. Let alone shoes not being meant to support you. Losing that, it becomes alot easier to "just go for a walk", or work on cardiovascular health. I got on it after I went on a trip with a friend and walking for a few hours had me bed ridden the next day and he was like "Ya, I'm tired but I could walk all day if I had to", and he wasn't fit. Now I'm that person and can fit in a whole meal with how much I burn from walking/running.
I will say for the time I was on a GLP-1 at the end, it's amazing. It's almost the same effect as the other pills on appetite, but without the side effects. Phentermine and other stuff will make people manic, paranoid, or make your heart pop out of your chest. This type of drug is a godsend, and anyone who's committed will maintain the weight loss and live a healthier lifestyle.
Religion is my assumption. Or human nature more generically. Gluttony is one of the seven deadly sins in Christianity. So it is a moral issue for many people.
“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.”
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.
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.
Family history of migraines and seizures, which some hypothesize have the same root causes. Would be interesting to see GLP-1 tests on epilepsy.
Why Does Ozempic Cure All Diseases?
I highly recommend 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....
Anecdotal evidence, anyone?
For me, prechewing pasta thoroughly knocked off 12-16 from my glucose level. (Converting carbs to dextrose in the mouth?).
These things do way way more than just appetite and craving suppression.
(Note: FOR SOME, not all, probably a small minority could be all)
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?".
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.