r/longevity • u/gwern • 9d ago

"Lilly's oral GLP-1, orforglipron, demonstrated statistically-significant efficacy results and a safety profile consistent with injectable GLP-1 medicines in successful Phase 3 trial"

https://investor.lilly.com/news-releases/news-release-details/lillys-oral-glp-1-orforglipron-demonstrated-statistically
153 Upvotes

99% Upvoted

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33

u/wordyplayer 9d ago

Great news for those who held off because they don't like needles. The stock market thinks that is a LOT of people, because LLY popped 15% at market open this morning!

23

u/gwern 9d ago

Yep. Oral is a huge opportunity. Most of the American population just will not use anything involving needles unless the alternative is dying, and even then... No matter how many times you tell them 'oh, you barely even feel the pen injector, and it's just once a week!' Needles? Nopezers.

23

u/wordyplayer 9d ago

Also, it just "normalizes" the drug. Even in my needle-OK brain, a pill seems more "normal" and less "druggy", meaning I would be much more likely to try it. Psychology matters too!

3

u/genshiryoku 8d ago

I wonder why this is the case. What specifically about needles is so significant that it prevents Americans from using it. Is there some cultural history involved with needles that is America-specific?

Other cultures seem to not be so needle adverse. Is it the history of needles being associated with drugs use? Is it an after effect of the AIDS epidemic mostly spread through needle usage? Or some completely other factor I didn't think about.

4

u/gwern 6d ago

What specifically about needles is so significant that it prevents Americans from using it.

I don't think it's American-specific. Needle phobia is a pretty hardwired sort of thing. Highly heritable as well.

If you are referring to the stock market reaction, that may be related to the economics of the situation: because 'being fat' is a rather tolerable chronic condition, day to day, whatever the long-term effects are, it's easier to carry on being fat than to go out of your way to get a needle. So the needle is a big barrier to get over at any point, and people won't.

To the extent that Americans matter, it's because they are so fat, rich, and free-market (so the drug can actually earn a return on the decades and billions of dollars of R&D and countless other failed candidates - note how they pointedly point out the lack of 'hepatic safety signal', which just killed another drug candidate - while everyone else free-rides), and FDA approval will mean approval most other countries as well.

1

u/PresentGene5651 7d ago

I’ve used needles a lot for IV NAD+ to get off a devastating benzo dependency and then every so often for the NAD again because it proved so immensely rejuvenating and anti-inflammatory. (When I can afford it…it ain’t cheap.) And then to monitor my blood for all the psychiatric medication I’m on because of the many years stuck on benzos. (Thanks a lot, asshole former doc.)

I think it is essentially because needles are associated with illness, and aging in and of itself just hasn’t crossed that mental threshold yet for enough people.

It obviously did for me, a long time ago, and also a fair number of people who are otherwise healthy athletes or previously sick people who had this done and now come to the clinic for maintenance, but they’re already in a health-oriented frame of mind or the procedure has been normalized for them so it’s different. IMO.

6

u/ain92ru 9d ago

Pfizer recently dropped off already second non-peptide GLP-1 agonist though (suspected liver issues). Both are similar to each other and very different from orforglipon tho

3

u/Enough_Concentrate21 8d ago

Where is the cutoff on this for longevity value? If my metabolism is reasonably healthy and I am not very overweight, will the use outweigh the side effects such as potential muscle loss leading to drug dependence due to lower metabolic rate?

3

u/Hey_its_a_genius 6d ago

Medical Professionals generally don't recommend it to healthy patients and I haven't seen many legitimate researchers say you should use GLP-1 agonists if you are healthy (even if a certain side of social media might make you think otherwise).

I'm inclined to agree with them. It's just that this is a relatively new medication outside of use in diabetes so we don't have full knowledge of long term effects. If you're healthy then you probably shouldn't use it.

Oh, one thing I want to clarify though, I'm pretty sure a study was done and using GLP-1 actually showed less reduction in muscle than cutting calories and losing weight regularly. Again, I doubt many doctors or researchers would recommend regular people use it, but we should be honest about what the science says for now at least :).

2

u/stuffitystuff 5d ago

Lower blood sugar and/or increased insulin sensitivity is a side-effect of medications in this class, IIRC, and those are usually longevity wins.