The Biochemical Beauty of Retatrutide: How GLP-1s Work
52 points
3 days ago
| 5 comments
| acesounderglass.com
| HN
mchusma
4 hours ago
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Retatrutide 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!

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mtdewcmu
27 minutes ago
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>> 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.

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nose
3 hours ago
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How 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.

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elteto
3 hours ago
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Wellness/Health clinics sourcing from China or compounding pharmacies, which themselves source the ingredients from China.
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SomaticPirate
1 hour ago
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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

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awakeasleep
48 minutes ago
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I don’t think anything you’re saying is outright false but the way you describe cessation as having an incredible rebound effect shows that you haven’t done very much research, that you’re negatively polarized, and that you’re trying to put spin on it
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QuantumGood
1 hour ago
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Start by looking at independent lab test results from multiple vendors, e.g. https://www.finnrick.com/products/retatrutide
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antinomicus
3 hours ago
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Yeah, I hear everyone talk about it like it’s just super easy to get…
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QuantumGood
1 hour ago
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Independent lab test results from multiple vendors, e.g. https://www.finnrick.com/products/retatrutide
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bsamuels
3 hours ago
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they buy it from research peptide vendors
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jfreds
3 hours ago
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I 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?
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the_real_cher
3 hours ago
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I 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.

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icameron
4 hours ago
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Does 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?
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cj
4 hours ago
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If 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!"

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taejavu
2 hours ago
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What’s wrong with eating steak? Biologically I mean, not ethically.
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fintech_eng
2 hours ago
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Absolutely 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.

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tptacek
1 hour ago
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A 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.

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stavros
3 hours ago
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That'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!

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cj
3 hours ago
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> 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.

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stavros
3 hours ago
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For 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?
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stavros
4 hours ago
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Unfortunately, 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.

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cj
4 hours ago
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How 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.

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stavros
4 hours ago
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> 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.

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zemvpferreira
3 hours ago
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Sorry 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.

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stavros
3 hours ago
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Thanks, everyone else I know who's tried it has had great results, I guess I'm just unlucky :/
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gedy
3 hours ago
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Everyone is different but I lost over 40lbs just by taking 5mg over about 5 months
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asdff
2 hours ago
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Now 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?
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ribosometronome
2 hours ago
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The issue is not lack of knowledge about appropriate amounts to eat, it's the physical sensations and mental state of being satiated at those amounts and the self control to limit yourself when you are not.
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cwyers
1 hour ago
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I was on a GLP-1 a few years ago and lost 70 lbs. After I got off, I kept a ton of diet changes (no more Pepsi or Gatorade and a lot of water instead, switching to whole grains and fiber/protein variants on pasta, etc.) and gained the weight back in a year and a half. The literature backs this up: keeping up weight loss is hard.
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n8cpdx
1 hour ago
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I’m hungry right now. I should be working, but all I want to do is to eat. I have already eaten more than enough today, and I would like to lose weight.

I could take more caffeine to reduce my desire for food, but it is already too close to bedtime. I could try to focus on work (I am) but I keep getting intrusive thoughts about the fact that I could just get ice cream/cookies/chicken fingers/burrito/quesadilla/insert food here in just a few moments.

I wish I could take these drugs, unfortunately I cannot. Terrible side effects.

Strangely, after visiting Japan I found it quite easy to eat a healthy low calorie diet for about two weeks. Now I’m back to constant food noise, despite trying to stick to a Japanese-style diet (lots of fish and vegetables and fermented foods).

The people who say “just eat less” don’t understand what the actual problem is.

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malfist
1 hour ago
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The people saying "just eat less" are the same ones telling depressed people "just smile more"
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gpt5
2 hours ago
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All 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.
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asdff
2 hours ago
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Weight 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.
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OkayPhysicist
1 hour ago
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You 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.

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rimunroe
1 hour ago
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> I would think that would be hard to do if you've already seen what appropriate portions are.

This would be true if not knowing what an appropriate portion size is was the one thing keeping most people from losing weight. If that was the case, traditional dieting would have a far better track record with long term weight loss.

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malwarebytess
1 hour ago
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Except if your body is unnaturally screaming at you to eat more. The obesity epidemic is not caused by ignorance or lack of willpower. It's natural differences in how people's bodies work compounded by modernity's changes to physical activity levels and diet.
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glp1guide
2 hours ago
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I 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!).

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malwarebytess
1 hour ago
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These 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-a... https://pmc.ncbi.nlm.nih.gov/articles/PMC11202225/

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caycep
2 hours ago
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Author 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...

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zoba
3 hours ago
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I hope it is more effective that Tirzepatide of which I am a rare nonresponder and have only gained weight.
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