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Comment by ramoz | Hacker News Reader

Can you explain what sucks about being on the prescriptions?

Hi there - Mounjaro user here. I've been using it for about a year at this point.

I feel sick for three days in a row after taking it. Even after several months on the same dose. I get horrible gut cramps, sour stomach, near constant nausea, and occasionally vomiting and diarrhea. I have to take my shot on Thursday night because I'll feel bad the next day and supremely sick the next two days. If I took it earlier or later in the week it would absolutely impact my ability to work during the work week.

It has had amazing effects. I've lost about 60 lbs in the last year and my A1c is now around 6.2.

It's a very effective drug, but it is brutal on my body. I'm not sure anything in the medication is causing the weight loss. It just makes me feel so sick that even if I'm hungry I don't feel like eating.

I mean no offense, but you have a fairly substantiated body of evidence that something in the medication is causing the weight loss. The side effects do sound really shitty though.

These medications don't work in the way many people think. The drug doesn't make you "lose weight" in the sense that it causes the body to excrete fat. Rather it interferes with the constants in the gut/brain signaling/programming system such that your brain doesn't want to eat as much. That in turn leads typically to weight loss.

I dont think there is any confusion about that. How would "excreting fat" even work?

DNP makes you burn fat, so technically it’s possible. It’s also dangerous as hell.

It makes you feel less hungry. It doesn’t burn fat. Eat less + exercise = weight loss

I am aware of the mechanics, thanks.

Ok, my mistake

The effects of the drug have helped me lose weight in two ways - one intentionally and one as a side effect.

The medication does make me feel fuller faster, so I eat less when I do eat, and I stay fuller longer. This helps me lose weight because it reduces the number of calories I consume.

The side effects make me feel so sick in those days after that I am effectively fasting all day (I have a small dinner, but keep drinking water so I don't dehydrate). That helps in losing weight.

That said, my original comment was meant slightly tongue in cheek - I know it is effective, but sometimes it's kind of darkly funny to think feeling bad from it is having the highest impact.

I’m curious what your diet is like, especially at the end of the week when the medicine is weakest. If I eat dairy, sugar, etc in the day or two before my semaglutide, I feel similarly.

It's typically a salad for lunch, usually lean protein over a complex carb for dinner (latest this week was slow cooked pulled chicken over brown rice), and typically a piece of fruit and a hard boiled egg for breakfast.

The hardest part about this diet for me has been finding sources of protein that get me at my goal with the small sizes of the meals I do eat.

Well that’s pretty clean.

I don't know how overweight you are, but could you not just reduce the dose to get fewer side effects & still have reasonable weight loss? & Did you try other GLP-1s?

I've lost 120 lbs from my peak weight. I have about 130 to go before I'm comfortable with my weight. I was severely overweight, now I'm just very overweight.

I am at the second dose up from the starting dose (5 mg vs 2.5mg), and the side effects are about the same between the two doses. They didn't start out that way, but they ended up at about the same level of misery.

I tried Trulicity when it first came out. It was not as effective, but the side effects for me personally were less.

I'm on Mounjaro for type 2 diabetes, not weight loss, so my main focus is on how it treats my t2d. The weight loss is a nice side benefit.

wow 120 lbs is amazing.

Good for you, that's incredible

These are pretty extreme side effects for being on the drug thus long.

What dosing are you on? If you’re still doing 2.5mg (smallest available in the auto injectors) perhaps try a compounding pharmacy for a month or two and you can experiment with lower doses and a different dosing schedule?

During my peak weight loss period I found that matching my injection schedule to the 5 day half life of Tirzepatide and adjusting the dose downwards to match this schedule helped with any side effects - including the “fading” of effects those last 2 or 3 days for me. There are half life calculator spreadsheets available on the internet that can help dial it in and keep your theoretical concentration more flatline vs peaks and valleys.

The current dosing regime is based on the single FDA trial that LLY did and is certainly not going to be the common practice a decade from now. It’s largely designed around patient compliance than anything else.

That said - everyone responds to this drug much differently. My little group I’m in is all over the map. Some folks lose weight consistently with tiny doses every 2 weeks, some are going above the recommended maximum weekly dose.

I also found food choices matter. A lot. The best part of tirz for me was being given mental space to stop eating shit food and start eating “clean” consistently. When on high dosing I absolutely would have a bad day if I decided to take my shot and then eat a typical American diet later.

The primary mode of action from the drug is simply you eat less. But it shouldn’t be due to you feeling too sick to keep anything down. That sounds pretty horrible.

I wouldn't trust a compounding pharmacy with making this given some of the truly horrible horror stories I've heard, and I'm on it primarily for type 2 diabetes. This is the minimal dose that keeps my A1c and blood sugar where my internal medicine doctor wants them. The weight loss is a welcome side effect. That said, I have lost about 120 lbs in the last two years, so something I was doing before I got on Mounjaro was working. Mounjaro just helped make it consistent.

tbqh being extremely overweight sucks in a whole lot of ways. While the side effects sound miserable, they will only be temporary. The damage done to my body and metabolism as a result of being this heavy for this long piles up every day, so if I have to suffer like this then I'd rather do that than have a stroke and die in front of my family.

Tried to list them all here:

https://glp1.guide/content/are-glp1-side-effects-all-the-sam...

It was a while ago, but IMO the list still plays

Oh also, the side-effect category is a good place to watch:

https://glp1.guide/tag/category-side-effects/

https://glp1.guide/tag/category-risks/

I try to tag all the new news of negative side effects there

Which of these are issues that diabetic/pre-diabetic/obese people would be likely to suffer from anyway?

And which of them are issues that people massively changing their diet and dropping weight, while also making lifestyle changes like exercising more (due to finding it easier after losing weight) would be likely to experience?

I'm just reporting my cached knowledge of people saying they experienced some adverse side effects. Also injections are not fun, even though they are probably a lot less annoying than they look.

In the 10 or so people I know who are on it, nearly all actually seem to enjoy it - reduced addictive tendencies/bad habits, appetite control, and reduced allergies seem to pretty well outweigh the minor side effects.

I was a heavy alcoholic, and the ability to quite drinking was... amazing. Now that I'm off, I just remind myself I never want to get back at that dark place, but I'm so very glad it made quitting just... happen. It's wild how easy it was. A little mental control in terms of "no, don't go to the liquor store" but it was habit more than physical addition at that point. This was with Rybelsus. Sober 4.5 years now. It was definitely not an intended side effect but I'm glad I was rx'd when I was. I was not in a good state.

Crazy to hear all these stories. My wife’s friend was a pack a day smoker for a decade that had transitioned into a heavy vape smoker, normal weight but couldn’t get off vaping despite trying. She tried Tirz to see if it would help and after only about 3 months she quit entirely, now completely smoke free for two months.

I'm on semaglutide for weight loss purposes, while having no other health issues relevant here.

I don't think it's made any difference to any addictive tendencies or my bad habits (and with ADHD, those certainly exist). It certainly helps with the appetite of course.

This is definitely anecdotal evidence, but it's wise to hold on longer for more data to come in before advocating for it on those grounds alone.

Too many miraculous stories so far I’ve heard, numerous people close to me quitting lifelong addictions cold turkey within months of starting.

I’ve never had an addictive personality but I also found I gave up a couple habits while on it.

I wonder if ADHD specifically isn’t as prone to positive effects there.

I’m INVESTING more. I’ve paid off like $15,000 in debts this year. I swear it’s because of the Zepbound.

Strange side effect, but maybe because you are happier? :)

I’ve lost 80 pounds before GLP-1s were a thing and didn’t gain this superpower, and the last time I lost weight (about ten years ago) I went from front line desktop support to teaching myself to code and getting a job as a software engineer, so honestly maybe it’s just “not having sleep apnea”, then when I regained the weight it felt like I lost some IQ points. So you may be on to something. Also it seems to generally reduce inflammation.

My heartburn I suffered from is completely gone but that’s because I just absolutely stuffed my face, I felt like I could never eat enough food.

A once-weekly subcutaneous injection is not a big deal for most people I think, outside of those who are very afraid of needles. It's a tiny needle and you don't even feel it. I've given injections to people who are afraid of needles, and they sometimes close their eyes in fear and are begging me to "just get it over with" without even realizing that I'm already done. Anyway, all this to say that outside of needle-phobic people I think the annoyance of the injections is probably not the reason people stop taking GLP-1 agonists.

> It's a tiny needle and you don't even feel it.

I'll add that while it isn't a big deal, I definitely feel the needle; sometimes worse than others. (I'm using 8mm 30 gauge needles.)

You have to inject it correctly, it needs to be injected in the fat and with the right angle.

If you have very little body fat, your glutes are probably a better place.

Source: I take HCG and have to use injection 2x a week. 27G is my favorite..

https://medneedles.ca/products/1ml-27g-x-1-2-sol-care%E2%84%...

It’s mostly random and some people do feel it more than others.

It’s a rapidly absorbed peptide suspended in water, it could even be used with a transdermal patch, so it doesn’t matter that much where it gets in or how deep. Best to avoid painful areas though.

It is correct (belly). :-) I think I remember it being less painful when I was fatter? The 30G/8mm needles I'm using are smaller than your 27G/13mm needles in both dimensions; should be better, if anything. Again, it's not a big deal, but I feel it.

As someone who is mildly needle-phobic, I'll agree it's no big deal, but you definitely can feel it, and if you hit a blood vessel by accident, there's a (mostly painless) bump and 2-3 week bruise at the injection site, which might be a major issue for some.

Be sure to pull back on the plunger and ensure there the needle is not in a blood vessel (pulling back will draw blood into the thing and you will see).

You do not want the drug meant to subcutaneous to go into the blood steam. This is true for GPL-1s (all peptides for that matter), as well as insulin, and definitely mRNA vaccines.

Mounjaro uses a single use fully autometed injector--clean your skin, remove the cap, press the injector against your skin, then press a button. A springloaded needle penetrates you skin and a spring loaded plunger injects the medicine. You have no way to pull backthe plunger to see if you are in a vein/artery.

I've never used Ozempic, but my understanding was it used a device similar to insulin pens--dial you dosage, attach needle, insert needle, press at the base of the pen to inject the selected amount. Also no way to pull back to see if you hit a vein/artery.

This is right. It's all or nothing, and there's no "pull back" functionality.

Only on the autoinjectors. Not true with the vial and insulin needles.

Yeah, both Ozempic and Trulicity have automated systems like this, just press a button and pop. Is there even a way to hit a vein? The needle is not very deep (it's subcutaneous, just barely under the skin). And it's the stomach, which AFAIK, doesn't have a lot of exposed veins?

Either way super simple and quick. Fairly painless. I had a weird rash one time, but apart from that a total of about 15 injections haven't had any issues on either Ozempic or Trulicity in terms of injections. Others may have difficulties, but it's been super easy IMO.

You can get these drugs with a vial and needles and it’s cheaper that way. Not familiar with the autoinjectors, but the instructions when using a vial and insulin needles is definitely to pull back.

Peptides don’t have the same negatives as say insulin, but preferable to not have them in your bloodstream nonetheless.

> And it's the stomach, which AFAIK, doesn't have a lot of exposed veins

And it's mostly for people who have plenty of stomach fat, so even less chance of hitting something else.

Mounjaro uses very different designs across the world. The UK has an included needle; here in Germany you need to get them yourself, and neither is an auto-injector.

Absolutely do not do this.

I understand if you have an autoinjector, you _can't_ do this, but this is how I was trained to give injections as an EMT-B (and paramedic training provided by the Army, as I was an Army medic).

It was common practice at some point, and keeps being taught, but it's no longer recommended even for IM by most medical associations (unless your injection site is considered high risk; but that pretty much is never the case for SubQ 4-6mm with 4-6mm needles).

I went down this rabbit hole after being handed a 100 pack of insulin needles and an estradiol vial with zero instruction - seemed irresponsible at first, but it turns out it's pretty hard to mess up.

This is incorrect, always do this. Its called aspiration and it ensures you are not in a vein or artery.

It's no longer recommended by most medical associations or the WHO.

https://www.cmh.edu/siteassets/media-documents-for-depts-sec...

SubQ has an even lesser risk of hitting a blood vessel.

Not sure why you are being downvoted. Some of the people using the brand name medication have some sort of auto-pen style injection but anyone using generics simply injects with an insulin pin. I always just pull back on the plunger (aspirate) before injecting. I currently take 18 shots a week (I'm very pro better living through chemistry) and do this every time. No issues.

You can get a vein finder to avoid that

You don’t feel it most of the time, it’s actually random with the sparse placement of nerves. Maybe 1 in 5 still sting a bit.

I take 18 shots a week - Big fan of better living through chemistry I don't even notice the SubQ shots anymore. The only annoying part is I have to lean forward to find enough belly fat when I shoot there. Still not a huge fan of the IM injections into my legs but we all suffer for our art.

Subcutaneous shots with insulin needles are basically painless. You don't even feel a prick, it's just a little pressure and then it slides in. When you get a shot at the doctor it's painful because they're intramuscular.

Once daily pills will very likely replace injections in the near future.

Eli Lilly will soon release key data on its weight loss pill orforglipron - https://news.ycombinator.com/item?id=43465346 - March 2025

https://en.wikipedia.org/wiki/Orforglipron

There's already Rybelsus. It's a bit more of a pain though as it needs to be taken on an empty stomach and you then need to wait 30-60 minutes before eating.

Looks like the benefit of orforglipron is you can take it whether you’ve eaten or not.

I've taken these and self injected, and it was surprising that I really felt nothing - no pain at all. I suppose because they recommend in stomach, and it's not in muscle, etc.

There's an auto-injector mechanism, at least with my brand; you don't need to needle yourself

Ah, auto-injectors, a curious piece of technology. I've always wondered how it is to actually use one since we had these in everyone's medkit in the German army, loaded with nerve agent antidotes. Just slam it on you leg and inject through the pants were the instructions... Kinda grisly, I guess it's less emotionally charged for a weight loss drug!

For drugs like these it isn't that different from a normal injection.

The pen has about 4 doses in it so you twist it to set your dose. You attach a needle tip to the pen and give yourself a poke, press an inject button on the top and a spring loaded ratchet system pumps in the dose amount you set (making a wonderful ticking noise as it progresses). Pull out and toss the needle and put it back in the fridge for next week.

I do manual injection which involves doing the full prep work. It takes about 3x as long to setup but is still only about a 3-5 minute process in total.

Thanks!

These tend to cost more than self-injecting. Maybe your insurance covers it and you don't care.

I had terrible side effects with Ozempic but have had minimal side effects with Zepbound that have disappeared over time. I just wake up on Thursdays and inject it first thing.

The auto pen misfired the other day and I called Eli Lilly and they immediately emailed me a voucher for a free 4 pack of the shots. It’s also eliminated my sleep apnea (via the weight loss).

I cant think of anything. I take 18 shots a week, including the GLP-1 shot once a week. I don't even notice it. I even give my wife her shot. Gotten to the point where I don't have a lot of belly fat to inject into so I have to lean forward but that's really it. I've never had a side effect from GLP-1. No nausea, nothing. Only side effect is I now have the will power not to kill a pint of ice-cream after 6pm. Its been 100% a willpower increase for me vs a physical change. Started in January at 240lbs. 210.8lbs as of this morning. Every ab is defined. Stuff is great, no idea why anyone would want to come off.

I can still eat whatever I want I just choose not to. For example, had burgers, fries and ice-cream for lunch on Saturday with the family and then just a protein shake for dinner.

I also don't snore anymore. I used to snore terribly, my wife would wake me up at least once a night to tell me to roll over. Not at all now.

Most importantly, even though I am on a ton of test and deca, my blood pressure is normal, and my cholesterol has actually gone down.

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