I do have a medical degree although I no longer work in that field. In the end it is the very long slow and extremely expensive research that produced these medications and other peptides.It is a bit of a pity the drug companies have chosen to price glp medications at illegal drug prices, which inevitably leads to a black market in them if there is demand, the market for mostly ineffective over the counter weight loss medications is enormous. For weight loss therapies that actually work, I suspect a very large percentage of the first world population will end up taking them with a decade or so, once there are so many competing medications that the prices have to come down. But at the moment a pretty large percentage of the population cannot afford their current prices, including me.
In the end it is the science that makes the existence of these medications possible, and does trials on hundreds or even thousands of people to find out if they work and how safe they are. There is zero doubt that semaglutide and tirzepatide are safe, it has been proven your chances of dying overall are lower if you are taking them than not taking them. Retatrudide is most likely safe, the first set of studies are done but the biggest scale stage 3 trials are not, and a lot of potential drug candidates still fail at this stage, even after good phase 2 results and usually because of unanticipated adverse effects. Pretty unlikely for reta, given the similarity to the others and the way it works is well understood. Nearly everything else on the price lists I have seen is far less well studied, and I spent a couple of weeks looking up most of them on google scholar. Some are outright lethal like DMP, but most show interesting potential in animal trials and most have not been tested in humans, which makes them medically unsafe. If you want to use them anyway, I actually have no problem with that, but unexpected and unpleasant side effects are definitely possible. And placebos are often very effective therapies for the peptides that don't really do much.
I am not claiming to be an expert in pharmacology, but I don't see much evidence for tolerance being an issue with these medications. People do develop tolerance to many different drugs like alcohol or opiates and more , but tolerance is not an issue for the vast majority of medically used drugs. People do not need to stop and start or change their blood pressure or heart or diabetes medications due to tolerance. I am trying to think of drugs it applies to that are not sedatives or opiates and not coming up with other examples.
Individual experiences can vary. I was pretty surprised when I swapped to tirzepatide, after a year of dosing ozempic at 0.2mg every 2 days to try to get less hungry without feeling too nauseous. And I expected from the research that tirzepatide would be a bit better. I managed to get the dose up to 15mg/week in a month with less nausea than 0.8mg/week of semaglutide and it is probably about as good at suppressing hunger. Which I cannot possibly afford at Australian prices of nearly $200 a week. Which led me to this forum.
Subjective experiences of medications or drugs are important, but there are some things that you cannot determine that way, only by objective testing and often only by enormous very expensive large scale trials, especially if you want to be sure one in every 1000 people who take something will not develop a serious unexpected problem. And even semaglutide and tirzepatide can and have caused deaths, most commonly in diabetics who develop nausea and vomiting, get dehydrated then develop renal failure and eventually die. Not common but is is not especially rare, in the general order of about 1 per 1000 to 1 per 10000. And this is an acceptable risk if it is proven that the benefits significantly outweigh the harms, and people give informed consent, although I doubt many doctors actually tell their patients of this particular risk. I know mine didn't.
