That’s pretty bleak. Imagine losing 100, 200 pounds, maintaining for a few years at a lowish dose, then it stops working and you slowly regain all that weight. That’s some Flowers For Algernon shit right there.
Not a phenomenon observed in 10,000+ participants in the pharma trials, including the multi year extended phases. No loss of efficacy with continuous exposure.
However, "it stopped working" is a common theme among non-pharma users.
It's important to understand that immunogenicity isn't usually binary, ie, it happens or it doesn't. It's often there but just kept in check. With x dose, diluted to x ratio, at x frequency, without interruption, it doesn't rise to a level where it compromised efficacy.
So you take one dose, the immunogenic reaction peaks at, using an arbitrary scale of 1-10, 5. A week later it's dropped to 3. You take another dose (another "exposure event") it peaks at 5, drops to 3 by the next weekly dose, and back up to 5 and so on, remaining at a stable level.
Now you take a "drug holiday", an extended break from use, immunogenicity drops to 0, but in the absence of exposure to the peptide your immune system builds up a nice supply of "memory T-cells", a "rapid response team" for future "invasions".
You take another dose after long break. immunogenicity response jumps to 8 and the drug is much more rapidly cleared from your system. A week later it's down to 5, and with the next dose it's back to 8, rapidly neutralizing the peptide, so the only way to get the same effect as previously is to increase the dose.
And there are other factors. We know from the trials there isn't a problem with 1 "exposure event" per week, but microdose and now you've got 7 exposure events, giving your immune system daily practice on ridding itself of this "infection". And ironically, small doses are often worse in terms of creating immune responses than larger ones.
So that's why screwing around with what's proven effective long term is so risky. In some individuals, this unwanted "enhanced immune response" can last for years. or even a lifetime.