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.
Currently the only people experimenting with it are the underground gray market peptide enthusiasts (you can find them on reddit and elsewhere), but the results are quite intense.
[EDIT] Just to be clear, gray market Retatrutide is illegal, I'm not encouraging you to buy it or do even take GLP1s in general. The point is that we have a preview of anecdata from people (with obviously high risk tolerance) taking this drug.
> If Eli Lily is the only producer, how is the gray market being supplied? This makes no sense...
It turns out enterprising chemists and pharmacists are capable of reverse engineering.
I don't think it's that hard to figure out how someone might do it -- imagine having to reverse engineer food you've received, given many samples. Imagine some of those samples might have "fallen off the back of a truck".
> That being said, I'm waiting for oral GLP1 agonists. Injections are a hassle and gray market ones even more so
This is really going to be the second leg of adoption and will catapult GLP1s even further IMO. Rybelsus has not really seen a ton of popularity compared to the injections. That said, Orforglipron is Eli Lilly's upcoming oral GLP1 and it looks to have really good results:
Yes, chemists don't need to reverse engineer that (although they can) because it will be in the patent. I'm not sure if the production process is though.
It's completely illegal -- the drug is not for sale, obviously is not FDA approved, and is not manufactured anywhere, the only safe/legal way to get it is a via an ongoing trial:
As one might imagine though, capitalism found a way. A LOT of compounding pharmacies are now very good at manufacturing GLP1s (not necessarily the case that the knowledge transfers, but I imagine networks/knowledge sharing groups do), so gray market has sprung up to supply adventurous people with Retatrutide.
I don't know about how hard it is to manufacture GLP-1 agonists specifically, but there's an existing enormous grey/black market for peptides for bodybuilding.
It started in the 90s with synthetic GH and since then the number of research peptides has exploded, all of which are readily available on the grey market.
So all the infrastructure for producing and distributing peptides was already there before GLP-1s were a thing, which probably explains why it didn't take long
Why is it illegal? Are drugs illegal by default or has it been specifically controlled/scheduled?
I looked up which drugs are scheduled in the UK and found the list is about 100x longer than I thought it was and in fact the government don't even publish a definitive and exhaustive list of all substances.
At least in the UK, drugs are legal by default in the sense that a specific chemical has to be classified under the misuse of drugs act to be a "drug".
However, specific classes of drugs (synthetic cannabinoids and substituted phenylethylamines etc.) are banned in their entirety by designer drug legislation. This is to stop people producing stuff like mephedrone etc., because there's an almost endless potential for minor chemical substitutions while still retaining the effects.
AFAIK peptides are not covered by any of that legislation, so they are a grey area, hence why they get sold as "research chemicals" "not for human use" etc. Separately it's probably illegal to produce patented drugs like semaglutide through non-official channels, but that would be a civil/commercial matter, not a drugs offence per se
Well for one they're flying in the face of the patent protection in place for Retatrutide -- that said the legalities around distributing prescription drugs or unknown chemical substances is murky (hence "gray" market).
Why use something which appears to have very similar results to tirzepatide/mounjaro but hasn’t been used by tens of millions on people without obvious issues like tirzep?
Yes, so far my preference has been Tirz. Though cost for Sema is significantly less.
It could also be the case that the dose on the Reta I used was too low. I've had a few people mention that they also felt it was fairly weak mg-for-mg, maybe 10mg would have been better.
There is a newer formulation, combining Sema with Cagrilintide that is probably the most effective option atm:
This is a valid concern but the subreddits I'm thinking about are not quite that -- no one is selling or trying to push you to some distributor, it's a lot of the bodybuilding/peptide crowd. More like walking into a classic forum thread than modern reddit. You can tell by the comments.
Just to be very explicit here, my profit incentive is selling newsletter subscriptions not selling drugs, if that was the worry.
The thing is that we just won't get any high quality data from the official trials for a very long time, but it looks like it's going to be even better than Tirzepatide which is the current king.
Outside of being simply well-researched, the best thing about GLP1s is that they are safe enough to be taken by millions of people (and they are) -- so anecdata is valuable. It's valuable to know what the "first adopters" are doing and what they're finding and what trends show up there.
[EDIT] Maybe I'm reading the comment wrong -- to answer with good intent assumed, I think GLP1s are basically the answer to obesity on any reasonable time frame.
GLP1s not the answer we wanted (most people would have preferred better food ingredient regulation, more people choosing healhtier lifestyles, etc), but it's the solution we're getting, it seems like.
Right now the only thing I think most can do to help this wave along (unless you're a drug manufacturer, insurer, or politician) is to share as much information as possible on positive and negative side effects, how the drugs work, why they work, etc.
[EDIT2] - Clearly there was no positive intent. I guess it's my own fault I took the time to seriously respond.
The original comment (now edited) was a question about me seeming like a disinterested third party and asking why I am discussing a gray market drug.
> I'm not a fan because it's expensive and once you go off of the drug the weight comes back on (at least from what I've read). That's not a trade-off I want to take lightly.
The rest of the incorrect points other people have basically covered, so won't repeat.
Is teaching the discipline lesson worth the shorter life people would live without this medication? Maybe we could find another way to teach people discipline that doesn't maintain a threat to their health?
> I don't find any of that unreasonable to me. I'm saying this as a type-2 diabetic who could stand to lose a lot of weight.
Gonna be incredibly blunt, but talk to your doctor and get on GLP1s. Take a low dose if you want.
GLP1s are incredibly well researched and effective. Imagine dying of a heart attack early because you refused to properly research effective, low-risk medication that is being used by millions and recommended by professional organizations and doctors widely. Real Steve Jobs energy.
We also like to keep track of all the bad ones too[0] (tl;dr they're actually pretty reasonable).
It's amazing what lowering inflation, reducing body weight can do to the body. It's almost becoming irrelevant that GLP1 Receptor Agonists were originally for type 2 diabetes (i.e. reducing HbA1c) -- the effects are profound. Kidney health, heart health, overall health, longer lives -- all for the low low cost of gastrointestinal problems (which can be serious, especially if dehydrated).
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