Yes, I have experienced it first hand, years ago, along with others with me experiencing a similar effect. It was so much weaker than my first "cycle", I was under the impression my second batch of Semaglutide was bunk, yet 2 others using it for the first time disproved that impression.
This was years before I came across other's anecdotes of similar experiences.
Then during a study of Tirz, researchers noticed a subset of subjects who had used short acting (diabetic treatment) GLPs and stopped, years before, uniformly had a weaker response to Tirz.
Now here and there clinicians will mention their patients hit a plateau and take a "break" to "reset" what they think is tolerance, a fundamental misunderstanding of the way the drug works. Again, like a "diet pill", and not a hormone. Only when they return, higher doses are required to recover the same level of weight loss.
This is hardly going to draw a lot of "high powered" research when there's a list a mile long of other aspects of these compounds waiting to be looked more deeply into. Just like you shouldn't expect research on the effects of stacking Reta and Sema or any other non-pharma protocol any time soon.
As for "it stopped working", did it? "Stopped working" means regaining the weight lost while on the same dose, and I don't hear that. In fact, the 3-4 year extended clinical trial phases of Tirz & Sema, with more than 10,000 subjects show nothing like that happening.
I keep using this analogy because all the clinical evidence and patient experience aligns with this.
GLP class drugs lower your metabolic "thermostat" on a dose dependent basis. When that weight "setting" is approached, appetite suppression weakens, then stops. But if you regain weight, on the same dose, appetite suppression returns as the body regulates appetite to return to homeostasis. This is why users of a maintainance dose maintain the same weight (roughly) for years, without further appetite suppression or side effects. It's not a diet pill. To lose more, increase the dose, the "setting" is lowered further, and appetite suppression returns until weight drops to whatever equilibrium level for the new dose is reached.
As to whether the observed weakening effect is only related to appetite or the other health benefits as well, that's a compete unknown. It'll probobly be years before we get answers as to how and who this affects. Diabetics aren't jumping on and off, so there's not much to be discovered with them. Pharma weight loss users aren't typically starting and stopping repeatedly. They either get to a maintenance dose as advised in the prescribing instructions, or they just come off.
And intentionally doing this to subjects when the research is of a potential harm will make it hard to get approved.
I will say this. The "failure" rate and "non responders", seem to be exponentially higher among the "do it yourself" crowd than those on the pharma protocols.
