I keep track of GLP1s and write a lot about them (looking for negative side effects, research results, etc) and it is amazing how potent retatrutide is. It’s not simply a matter of “more agonists, more better” but it looks like Eli Lilly has really cracked it.
There is a large enthusiast community of the body building variety (who are usually first) who are already performing a bit of an unscheduled human trial and I have to say the results are amazing. We have both injectable retatrutide and pill form retatrutide to look forward to (pill form is unannounced but I have a hunch!).
Addiction comes up in anecdata all the time so I've written about it a few times but these papers are a good place to start to find more rigorous data points.
Eli Lilly has taken to calling GLP1s "anti-hedonics" as well
Just stating the obvious -- losing weight (and likely lowering HbA1c/having other benefits) for 18 months is probably infinitely better than never losing weight at all.
> Of the 308 who benefited from tirzepatide, 254 (82 percent) regained at least 25 percent of the weight they had lost on the drug by week 88. Further, 177 (57 percent) regained at least 50 percent, and 74 (24 percent) regained at least 75 percent. Generally, the more weight people regained, the more their cardiovascular and metabolic health improvements reversed.
So weight loss was actually maintained for most people -- the hard part is finding a healthy daily lifestyle which can maintain the drastic effects of GLP1s.
This information isn't new -- weight regain has been studied before and I've written about it before:
The missing piece to this article is just how bad the alternative is -- never having the cardiovascular and metabolic benefits is clearly not the best strategy (and if simply changing patterns was so easy, people would have done it already).
GLP1s don't work for everyone but they're pretty close to miraculous in effect given the balance of positive and negative side effects. Making GLP1s cheaper & more tolerable then figuring out how to actually deal with the complex web of how to keep the weight off sustainably for most people seems like the right way forward here, not avoiding potentially life-saving medication because you may not be able to get off of it as fast as you want (if you can afford it).
BTW, there is already generic Liraglutide, and legal workarounds for getting compounded Semaglutide that already mean no one pays the $1000 that was in the zeitgeist a while ago. Even Lilly Direct and similar outfits from Novo sell for $500/month, with the $150/month pricing coming soon[0].
> So weight loss was actually maintained for most people
Unless I'm mistaken, how can you interpret that from an article that claims that 57-82% of participants regained 25%-50% of their weight loss, with 24% regaining at least 75% of it? In just a bit more than a year and a half, too.
Like others have mentioned, liraglutide already exists as a generic! It's not as good as Semaglutide or Tirzepatide, but.
Also, a lot of people are still getting compounded GLP1, to the chagrin of Eli Lilly and Novo Nordisk.
Separately, 2026 is about to completely change the pricing of this stuff, not even taking into account the Trump administration's recent efforts. The price of injected GLP1 is going to implode due to patents lapsing in Canada and other places -- and for the pill forms that come out soon it looks like the Trump administration is keen on keeping prices for that low as well.
At this point most experts lean more heavily on the effect of GLP1s in the brain rather than delayed gastric emptying -- it's more of a brain drug than anything else which is why it works so well.
Basically, the gastro-intestinal side effects are the biggest issue, along with CVS (not the store) and possibly eye problems.
That said, the negative side effects look to be incredibly rare and manageable (including via stopping treatment) -- and the positives are quite tremendous.
It's not a magic drug, but it is the first of it's kind with such a skew to the positive on side effects.
Not only that, there is a legitimate raft of companies lining up to make generics.
There’s one wrinkle though, legally importing prescription drugs from Canada isn’t really allowed in the US/UK AFAIK. HIMS is probably feverishly figuring out how to do that right now.
Absolutely -- certainly in their biggest markets they'll be able to protect those patents.
Both companies have thus far been unable to really stop compounding pharmacies and/or gray market suppliers from replicating though, and price negotiation with the government is definitely going to happen (Trump recently announced wanting $150 GLP1s, Novo's lawsuit against medicare price negotiation failed)... I do not have much faith in their ability to protect their pricing power for very long, which unfortunate for them is probably what's best for humanity and is very well known at this point.
This was made abundantly clear to me in 2020. It's a mass hysteria fueled by trypanophobia in a vast population of people who aren't very interested in self-analysis and understanding how their own behavior and thought patterns are driven by the amygdala.
One bit of evidence for this: SARMS are huge in the bodybuilding as "gateway steroids". They don't work, they have bad side effects, but hey, they're oral.
A bit late, but thanks for noting this -- I had no idea that this workaround was so well established. I don't often dive into concrete suggestions on how to obtain GLP1s because of how it could be perceived, but maybe I've underestimated how many people know how to do this right now.
Do yourself a favor, and just take GLP1s instead (after talking to your health care professional). The research on the effects is plentiful, they're incredibly effective, and next year by next year you'll have very effective FDA approved (for weight loss) oral GLP1s to take.
Losing weight is almost solved at this point, I'd post links but at this point the substack I run is heavily paywalled -- the research is out there and not hard to find with a quick search.
That sounds like a terrible experience, sorry you and the wife went through that and somehow the negative side effects STILL persist. This is honestly the first case I’ve ever heard of such an adverse effect.
GLP1s are certainly not for everyone, and if she had that reaction on a starting dosage then it certainly is obvious stopping was the way to go.
That said, for the vast majority of people though, GLP1s are likely going to the key to living longer and carrying less weight (including into old age). At this point, the research is behind the drugs being useful for the vast majority of the population, and the literal millions of people taking these drugs do not seem to be running into such horrific side effects, especially ones that continue after stopping the drugs.
Would you mind sharing which GLP1 she was on? This actually sounds like something that should be more widely known. Throwing up forever is quite a crippling side effect, and since GLP1s are more recently considered primarily brain drugs, I wonder if it triggered a persistent chemical imbalance.
There is a large enthusiast community of the body building variety (who are usually first) who are already performing a bit of an unscheduled human trial and I have to say the results are amazing. We have both injectable retatrutide and pill form retatrutide to look forward to (pill form is unannounced but I have a hunch!).