From blood sugar to brain relief: GLP-1 therapy slashes migraine frequency (medlink.com)

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.

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.

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.

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.

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.

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.

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.

It's Gila monster venom. You may become a druid while taking it.

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?)

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.

Anything dealing with the signaling systems of the body (GLP-1 agonists, DP-XX binders like Keytruda, IL-XX binders like Humira, etc and even HRT) all fall under this bucket. We have a great understanding of some effects of some signaling systems and we use that understanding to our advantage. But the fact is these signaling molecules and receptors do a lot, more than we know, and in overlapping and complex ways, that we are always finding “new indications” and “new side effects” with roughly equal frequency.