What Ozempic does to the gut-brain axis

I personally believe you are right to be weary about holding off on long term use before the long term efficacy and risk profile of a drug has been established, but GLP1 class drugs have been around for a long time now.

GLP1 agonist type incretins have been available for over 20 years at this point. The first marketing approval was in 2005 for exenatide (Byetta), indicated for T2DM. Exenatide was the first in class for GLP1 agonists. Then came Liraglutide (Victoza) for the same indication around 2010, and received marketing approval for weight loss (as Saxenda) 4 years later. After that around 2017 was semaglutide (Ozempic & Wegovy).

T2DM is a chronic disease, so patients who started exenatide had to stay on it life long.

These drugs are nothing new and were already being used for T2DM. It only caught public attention because semaglutide achieved double the mean BW loss over liraglutide, making it meaningful for weight loss. Novo Nordisk first got approval for Ozempic for T2DM in 2017 and then received approval for it to be marketed for weight loss under Wegovy only in 2021, but by then clinicians were already prescribing it off-label, strictly speaking, for weight loss.

I don't know how much we could extend this "they've been around for a long time" to tirzepatide (Eli Lilly: Mounjaro & Zepbound) because it's the first dual agonist. It targets GLP1 and GIP, and thus it's meaningfully separated from the others. This goes for retatrutide (again Eli Lilly) as well if it eventually comes to market as it would be the first triple-agonist targeting the aforementioned + GCGR, the glucagon receptor.

Not really, healthy person can easily handle that amount of sugar. Has plenty of fiber to balance.

I have lost 30lbs this year and even the difference between .5 and .7 is noticeable to me.

There is also the variable that you can work out too much. I did a brutal 30 minute glycolytic conditioning session on Friday and it just doesn't matter how much protein I consume the next day. Something with ghrelin goes off the chart and the next day takes huge will power to not just eat everything.

I think it is even worse with max effort weight lifting.

Definitely not a good idea to be on it longer than 2 months. If we can't treat the underlying condition and the patient needs life-long acid suppression therapy, we switch to H2 receptor antagonists, like cimetidine.

Long term PPI use has non-trivial risks, including magnesium and other micronutrient deficiencies, and can lead to things like SIBO and other primarily gut related morbidity.

I would definitely suggest sitting down with your doctor if you were not specifically instructed to take it for that long.

I think you are ignoring the selection bias, when looking at people who seek out professional help for losing weight, even more so when it's about people who can then become jacked.

Note that I'm not speaking as someone who has just accepted being overweight/obese. I was hovering around 105kg in my early 20s, then I gathered the motivation to go down to ~75kg over the course of a year, then maintained myself around 80-85kg for the next 5 years, then in a bad period went back to overeating and was hovering around 100kg again for a few years, and now I'm in the process of going back down (currently around 86-88kg after 6 months of actually working on losing weight - so about two thirds of the way to where I'd like to be, given I've also been building some muscle mass).

So I'm not someone who just throws up their hands and says "I'll always be fat", or maybe pushes themselves for a fad diet one month and is proud of losing 5kg that come back right away. My experience though is that appetite control and managing food cravings are the most important parts of managing my own weight, and that the nutrient content of food has virtually nothing to do with it. I can eat a whole steak with 400g of steamed peas and some asparagus, with some butter and cheese, and then feel hungry and unsatisfied 4-6h later when the stomach isn't as full. And if I'm not in a good headspace, I may well then grab a McDonald's menu to get rid of the feeling of hunger and get some satisfaction that the steak and vegetables didn't actually address on that day - and the exact opposite can happen on other days.

This is why for me things like One Meal A Day (OMAD) has been mucn more useful than actual careful nutrient tracking. Being able to tell myself "it's OK that I'm feeling hungry right now, I'll eat that X tomorrow and be satisfied" has been the single biggest helper. I've not yet been tempted to try out GLP-1s (afraid of the side effects, the food problem isn't that bad), but I imagine they could be a huge help if they removed the need for such willpower-based mechanisms.