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The Biochemical Beauty of Retatrutide: How GLP-1s Work
- mchusma 6mo agoRetatrutide is incredible in a mind altering way. I know 4 people on it, including myself. And all just love the way it makes you feel. You just don’t want to eat as much and you want to eat healthier. As far as I can tell, that is it. While I’m nervous there could be long term side effects, I think the health benefits of being at a healthy weight mean that for probably 50% of the developed world they would benefit from it. Looking forward to more formal studies though!
- icameron 6mo agoDoes it alter you mind more than just your appetite for healthy food like you said? Is there a buzz or general mood lift as well?
- cj 6mo agoIf there's any mental effect, it's most likely from eating less food (and most likely healthier food) and feeling better because of that. It doesn't increase your appetite for healthy food. It will punish you for eating bad food. "Don't eat that steak, you're going to have crazy stomach pain tomorrow if you do!"
- stavros 6mo agoThat's not my experience with tirzepatide. When it worked for me (which was a brief period, admittedly), it kind of turned me off fatty foods, and I wouldn't want to have pizza, for example, but I'd crave a chicken breast and boiled potato, or salad. When it didn't work, one of the failure modes was that I still craved fatty/fried food, but I got terrible stomach pain from it, which is the worst of both worlds. If I'm still going to be unable to resist food, I don't want to be punished for it any more than I already am by being overweight!
- cj 6mo ago> When it didn't work, one of the failure modes was that I still craved fatty/fried food, but I got terrible stomach pain from it I saw this was a feature, not a bug.
- stavros 6mo agoFor me, it was definitely a bug, because my issue is I can't restrain myself. I don't lose weight, I just get pains. If I could restrain myself, why do I need the medication?
- taejavu 6mo agoWhat’s wrong with eating steak? Biologically I mean, not ethically.
- fintech_eng 6mo agoAbsolutely nothing, if you only eat a few ounces. But a lot of places will server you a 12 oz ribeye steak which has 900 calories all by itself. Add on a side of french fries and a sugary beverage and you get a days worth of calories in a single sitting. When you are on a GLP medication, commonly your digestion slows and will make you really prone to constipation and acid reflux. I've learned to eat just 3-6 ozs when I do steak, and generally opt for the veggies instead of the potatoes now. Feel much better in the morning.
- tptacek 6mo agoA 12oz ribeye is a pretty generous serving; it's not something that sneaks up on you. The surprising thing for me, having settled into a ~1400kcal budget, is how tricky it is to hit protein goals. You go into this thinking it'll be like going low-carb, you'll just eat a lot of beef, but the fun cuts are not efficient protein delivery vehicles. Hitting the kcal budget is effortless; getting the protein in, not so much.
- fintech_eng 6mo agoSame! Keeping a small stock of these has helped me a lot with that: https://fairlife.com/core-power/chocolate-protein-shake-42g/ https://fairlife.com/core-power/chocolate-protein-shake-42g/
- taejavu 6mo agoYeah I think the fries and sugary beverage would be contributing to the “crazy stomach pain” a lot more than the steak. But the person I’m replying to made no mention of those things..
- fintech_eng 6mo ago
- stavros 6mo agoUnfortunately, my experience with tirzepatide doesn't make me hopeful: It either gave me terrible diarrhea and sulfur burps, or it did nothing at all, even on 15mg. Hopefully retatrutide is different, but I'm not holding my breath. It did work for around two weeks, though, and it was great. I constantly felt mildly carsick, so I didn't really want to eat anything, but also didn't have much trouble eating my macros.
- cj 6mo agoHow did you get to 15mg and only had it working for 2 weeks? The starting dose is 2.5mg and it takes many months to titrate up to 15mg. Most people never get to 15mg. I've read hundreds of anecdotal experiences from people on these drugs, and haven't encountered anyone taking 15mg without success.
- stavros 6mo ago> How did you get to 15mg and only had it working for 2 weeks? Shrug, it's a mystery to me as well. It did take many months to get to that point.
- zemvpferreira 6mo agoSorry to hear that. As a counterpoint for the peanut gallery I've been on tirzepatide for 5 months and lost 15 kg in the first 3 months, never going past a 1.25mg dose. I've only creeped up to 3mg since and keep losing around 0.3 kg per week. No side effects except for super mild nausea every now and then. I plan to stay at a similar or lower dose for the next couple of years. I had the good fortune of responding well and being at a great starting point: despite being 40% body fat I exercised a lot and had great labs to begin with. Anecdotally I've found starting metabolic health to make a huge difference in dose response.
- stavros 6mo agoThanks, everyone else I know who's tried it has had great results, I guess I'm just unlucky :/
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- nose 6mo agoHow is everyone purchasing Retatrutide at this moment? It's still in phase 3 trials, and I keep hearing of people being on it. Not really seeing safe options with proper lab testing. Other pharmaceuticals at the phase 3 stage (such as Buntanetap for Parkinson's disease) are super difficult to get, even with the right to try exemption in the US.
- antinomicus 6mo agoYeah, I hear everyone talk about it like it’s just super easy to get…
- QuantumGood 6mo agoIndependent lab test results from multiple vendors, e.g. https://www.finnrick.com/products/retatrutide https://www.finnrick.com/products/retatrutide
- deleted 6mo ago[deleted]
- bsamuels 6mo agothey buy it from research peptide vendors
- elteto 6mo agoWellness/Health clinics sourcing from China or compounding pharmacies, which themselves source the ingredients from China.
- QuantumGood 6mo agoStart by looking at independent lab test results from multiple vendors, e.g. https://www.finnrick.com/products/retatrutide https://www.finnrick.com/products/retatrutide
- SomaticPirate 6mo agohttps://www.ft.com/content/b15407bd-7b86-45c3-9780-0c92117ccbfb?shareType=nongift https://www.ft.com/content/b15407bd-7b86-45c3-9780-0c92117cc... They are buying from Chinese dealers. And sadly, as with most GLP-1s they likely will need to take them for the rest of their life or suffer some incredible rebound weight loss/ negative health effects. These medications are incredible if you are overweight and need them. But they are not a panacea. Also arguably buying these drugs from Chinese dealers means there is no recourse if you get a bad batch. There is a pseudo testing setup around Finnrick but talk to anyone with a PhD in biochemistry and there are numerous ways these molecules can be improperly manufactured. Surprised to see so many on HN being relatively careless with their heath
- jfreds 6mo agoI tried semaglutide and while it was effective for losing weight, it made working out impossible (felt exhausted and very sick as soon as hr went up) and it made hangovers awful. Is retatrutide any different?
- the_real_cher 6mo agoI got food poisoning on a glp2 and it was the worst I've ever felt in my life for like a week because it it slows the digestion. it was an edge case I had not considered.
- zulux 6mo agoAlso, when you need to vomit, GLP1 still makes your body think there's food left to vomit, and you can wind up retching for quite a while.
- the_real_cher 6mo agoNever again!
- ASalazarMX 6mo agoI'm surprised your doctor didn't recommend a laxative, because they know it slows digestion.
- tsol 6mo agoHad the same issue. With reta I have more energy than normal and workout even more than usual. I get great workouts despite eating around 1400 calories a day. I don't wanna act like it's without flaws but I gotta say it does it's job very well
- asdff 6mo agoNow that the drug has shown you what a more appropriate portion is, do you think you can manage that on your own without the drug?
- gpt5 6mo agoAll research points to a "no" answer - weight is regained, and quickly. Which helps explain why obesity is so prevalent - it is something in the brain's chemistry.
- asdff 6mo agoWeight would only be regained if you start eating more, no? I would think that would be hard to do if you've already seen what appropriate portions are.
- OkayPhysicist 6mo agoYou seem to have a fundamental misunderstanding of what GLP-1 agonists help with. In simple terms, they make you less hungry. If you stop the drugs, it's not surprising you go back to being hungry. It would be a miracle drug if you didn't. People, on average, eat until they're no longer hungry. Problem is, there's only a loose relationship between your caloric needs and your hunger response. That's how you end up with underweight people who are trying to put on muscle saying they can't possibly eat any more and still can't put on weight, while having overweight people who eat twice as much as that guy and have to actively choose not eat more. Both people can make a conscious choice to disobey their signals, just like how you can choose to hold your hand to a hot stove. But it takes a lot of energy to keep up that willpower. Effective weightloss drugs solve that problem, by treating the actual problem: the hunger.
- asdff 6mo agoI don't misunderstand. I understand they stop you from feeling as hungry. That is why it is even more perplexing. Eating until you are no longer hungry isn't how most people eat I'd say. Most people eat a given quantity of food. A plate of food. A bowl of soup. An entree with the provided side perhaps. People don't generally order food, eat it, and order more food. Maybe they do I guess, but I haven't seen it personally. I mean I think a lot of people could shove a dozen hotdogs down their gullet if they wanted to, but that reaction isn't a typical expectation. Plus once you've seen normal portions, surely you'd realize when you are going beyond those. Speed of eating might also be an underrated factor in all this. Stretching out ones meals and slowing down the pace might lead to satiety triggers coming before the meal is done, whereas if one scarfs down the plate before that signal happens, well, one already scarfed down the plate and might be working into the next before those signals hit. This meta analysis suggests this is a possibility (1). 1. https://pmc.ncbi.nlm.nih.gov/articles/PMC8156274/ https://pmc.ncbi.nlm.nih.gov/articles/PMC8156274/
- mtdewcmu 6mo ago>> Retatrutide is incredible in a mind altering way >> and all just love the way it makes you feel Maybe it will turn out to be an antidepressant as well. That would be quite a coup.
- rickydroll 6mo agoThere have been some hit pieces on Retatrutide that claim it blunts emotions, period. It was characterized as, "falling out of love with someone." Have you noticed anything like that?
- zoba 6mo agoI hope it is more effective that Tirzepatide of which I am a rare nonresponder and have only gained weight.
- aaron695 6mo ago[dead]
- caycep 6mo agoAuthor spent a ton of time writing this up "for fun"...but glad people are still doing this and old school blogs. The effort required seems substantial... Not sure about the AI style transfer images... sure it's a valid way to get the illustrations you want but I don't have to like it...
- glp1guide 6mo agoI keep track of GLP1s and write a lot about them (looking for negative side effects, research results, etc) and it is amazing how potent retatrutide is. It’s not simply a matter of “more agonists, more better” but it looks like Eli Lilly has really cracked it. There is a large enthusiast community of the body building variety (who are usually first) who are already performing a bit of an unscheduled human trial and I have to say the results are amazing. We have both injectable retatrutide and pill form retatrutide to look forward to (pill form is unannounced but I have a hunch!).
- malwarebytess 6mo agoThese GLP-1 drugs seem to do more than what the article describes. The spontaneous cessation or serious reduction of addictions (chemical, behavioral) and otherwise compulsive behaviors when taking GLP-1s is widely discussed and described. It seems like it does something else. https://sph.brown.edu/news/2025-07-24/brain-science-glp-1s-addiction https://sph.brown.edu/news/2025-07-24/brain-science-glp-1s-a... https://pmc.ncbi.nlm.nih.gov/articles/PMC11202225/ https://pmc.ncbi.nlm.nih.gov/articles/PMC11202225/
- arjie 6mo agoThe magic trick with these is the way to increase half life. It’s really quite an amazing piece of work. I used retatrutide for a while very effectively but then we’ve been traveling a few months and I’ve gained quite a bit of weight back as expected. The drug is pretty much ideal: dose-response curve doesn’t flatten too much, adaptation is present but not extreme, it is entirely reversible when you get off it. The side effects I see are a histamine reaction at the injection site and cold sensitivity. To stop the former I varied duration of injection, temperature of solution, and site. None of these had any effect so I just lived with it in a place it wasn’t too uncomfortable. I haven’t been lifting very much during the period immediately prior due to injury playing sports and reinjury due to inactivity after a motorcycle accident years prior. My peak lifts were @155 lbs: squat 265x5, deadlift 375x2, bench 185x1, ohp 135x5. Stating these so you know where to baseline. Immediately prior to retatrutide schedule: squat non functional (could not squat), deadlift 225x5, bench 125x1, ohp non functional (could not raise arms above head). Weight 199.3 lbs And I was also going to physical therapy. After schedule: squat 135x5, deadlift 325x5, bench 135x10, ohp 135x2. Weight 173 lbs 1.5 months after cessation: I didn’t increase lifts due to not having standard programming. Weight 182 lbs. Overall, an excellent drug. I should note that I ramped up slowly from under 1 mg/week up so my nausea and other symptoms were extremely minor. At lower doses I’d walk up to the fridge as I did in the past and then decide against eating a snack. At higher doses I wouldn’t get up. I already knew I should drink but I drink a lot of Coke Zero so that was fine. I never actually hit a routine dose that was within the tested range, I was always lower.
- UltraSane 6mo agoGaining fat means you are eating a caloric surplus