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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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?".

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.

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.

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."