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Discontinuation and reinitiation of dual-labeled GLP-1 receptor agonists

nautil.us

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Re: Discontinuation and reinitiation of dual-labeled GLP-1 receptor agonists

#101

Post by watermelon0 »

gpt5 wrote: post #41
TaupeRanger wrote: post #3

Kind of a useless analysis if it doesn't compare the risk after stopping GLP-1s to the risk of NEVER taking GLP-1s in the first place. We probably don't know the numbers yet, but one can easily envision a scenario like: risk of CE without GLP-1 weight loss: 20%. Risk after taking GLP-1s for 2 years: 10%. Risk after stopping GLP-1s: 12%. "Your heart attack chance goes up 20% after stopping GLP-1s!!!"

Especially since every GLP-1 study shows almost complete regain to original weight after stopping. It’s like stopping a blood pressure medicine and then being surprised that people have more heart attacks afterwards.

There is a recent one, which shows that the weight was generally stable after 1 year of discontinuation of GLP-1.

> In this cohort study of adults with overweight or obesity who initiated treatment with injectable semaglutide or tirzepatide and discontinued the index medication between 3 and 12 months after initiation, 19.6% restarted the index medication and 35.2% received an alternative treatment in the year after initial treatment discontinuation. The average weight change 1 year after index medication discontinuation was relatively small; however, there was considerable individual-level variability.

https://dom-pubs.pericles-prod.literatumonline.com/doi/10.11...

Re: Discontinuation and reinitiation of dual-labeled GLP-1 receptor agonists

#102

Post by walletdrainer »

cthalupa wrote: post #94
sublinear wrote: post #92

Earlier quoted context omitted.

Sorry, you're right. I meant that I did not make significant changes to my diet. My point was I didn't really change what I eat, but how I eat. I still hate certain vegetables like carrots, kale, brussel sprouts, etc. and just added more of the nutritionally equivalent and culinarily far superior vegetables I was already eating. That's not willpower. That's looking things up in the USDA database and tweaking my exist…

I'm not knocking anyone meeting their goals without GLP-1s. It's obviously possible in absolute terms - people have been making great body transformations for as long as we've had fat people. But everything you did, plenty of people try to do and fail at it. You are making it sound like this is all it takes and that it's easy. It might have been for you! But it might not be for other people. The fact of the matter is…

> A subcutaneous injection once a week is nothing

I do at least one a day, sometimes up to four if things happen to line up exactly right.

Even four subq injections amounting to around 2ml of stuff is nothing, doing all four of them after a shower takes about as long as brushing my teeth.

If you use correct technique and good quality needles, you will feel essentially nothing. If your needles are not sharp enough, there might be very slight discomfort when initially piercing the skin.

Re: Discontinuation and reinitiation of dual-labeled GLP-1 receptor agonists

#103

Post by gpt5 »

watermelon0 wrote: post #101
gpt5 wrote: post #41

Earlier quoted context omitted.

Especially since every GLP-1 study shows almost complete regain to original weight after stopping. It’s like stopping a blood pressure medicine and then being surprised that people have more heart attacks afterwards.

There is a recent one, which shows that the weight was generally stable after 1 year of discontinuation of GLP-1. > In this cohort study of adults with overweight or obesity who initiated treatment with injectable semaglutide or tirzepatide and discontinued the index medication between 3 and 12 months after initiation, 19.6% restarted the index medication and 35.2% received an alternative treatment in the year after…

Thanks for sharing. Note that the data quality from this study is quite low because 54.8% of the cohort eventually restarted their medication or transitioned to an alternative therapy (mostly a different weight loss medication).

I don't know why a study that focuses on discontinuation didn't split the groups that restarted or transitioned against the group that actually just stopped.

Re: Discontinuation and reinitiation of dual-labeled GLP-1 receptor agonists

#105

Post by r-johnv »

TaupeRanger wrote: post #3

Kind of a useless analysis if it doesn't compare the risk after stopping GLP-1s to the risk of NEVER taking GLP-1s in the first place. We probably don't know the numbers yet, but one can easily envision a scenario like: risk of CE without GLP-1 weight loss: 20%. Risk after taking GLP-1s for 2 years: 10%. Risk after stopping GLP-1s: 12%. "Your heart attack chance goes up 20% after stopping GLP-1s!!!"

They actually do compare against a control group. This is the study that is being referenced.

https://bmjmedicine.bmj.com/content/5/1/e002150

The data on the results section shows almost parity between the control group and participants who discontinued for 2 years.

Note that while it is a well conducted study at the US VA with 300,000+ patients, it is not a randomized study so fully eliminating confounding variables and reverse causality is hard.

Re: Discontinuation and reinitiation of dual-labeled GLP-1 receptor agonists

#106

Post by r-johnv »

kube-system wrote: post #9
IAmGraydon wrote: post #7

Earlier quoted context omitted.

>This is a very odd phrasing that makes it seem like heart attack and stroke risk are higher for those who stop taking the drug than those who never took the drug. That does appear to be the case, according to the study.

The conclusion of the study says: > This study showed that discontinuing and interrupting GLP-1RA treatment could erode and might reverse the cardiovascular benefits of the drug in a duration dependent manner, increasing the risk of cardiovascular events. emphasis mine

Reverse the benefits != increase the net risk

It took a while going through the data in the results section to see this.

Re: Discontinuation and reinitiation of dual-labeled GLP-1 receptor agonists

#107

Post by ErroneousBosh »

shlant wrote: post #85
ErroneousBosh wrote: post #16

Earlier quoted context omitted.

It doesn't reduce heart attack and stroke. It reduces appetite, kind of, and gives you a sore stomach while making you shit yourself inside out. All this can, with care, help contribute to weight loss. Weight loss can reduce heart attack and stroke, but GLP-1 does not. You could also reduce heart attack and stroke risks by not eating crap and going for a walk every so often.

> You could also reduce heart attack and stroke risks by not eating crap and going for a walk every so often. Oh wow it's so simple! why has nobody thought of this before??

You've been being told this your whole life.

You still think mass-marketed "low fat" foods are good for you.

You still think you can pop a pill to make your problems go away.

Re: Discontinuation and reinitiation of dual-labeled GLP-1 receptor agonists

#108

Post by phil21 »

pitched wrote: post #29
Teknoman117 wrote: post #26

I’m always kind of envious of the people who were able to lose weight on GLP-1 drugs. I lost a bunch of weight a few years ago, and still need to lose a lot more (430 lb -> 330, goal 240), but I fell out of the good habits for, well, no good reasons… Decided to try Ozempic and was on it for about 6 months. Didn’t do a single thing for my appetite unfortunately, even on the max dose. Sample size of one here, but if yo…

I really had thought (with no research) the correlation between mental health and glp1 effectiveness went the other way around. Thank you for this check-your-biases moment, you probably just saved me a ton of embarrassment down the line, if these drugs ever enter my life.

I don’t think there is remotely enough data on the subject to make any confident statements either way yet.

I think the only very confident thing I can say after watching and helping dozens of folks get started on these drugs is that everyone’s biology is vastly different.

I have friends who have lost close to a hundred pounds on the starting doses of their chosen GLP-1. I have other friends who barely lost anything after a year at max dose. Some of these people in both groups are highly motivated to lose weight and some are simply taking the drug as a magic fix and expending zero other effort into changing their lives. Some have very difficult mental issues and relationships with food, some have very few hangups on the subject.

I have never been able to predict with high confidence how any particular person is going to react to taking them. By and large the results are close to magical for the majority of folks, and there may be some correlation with folks who combine the drug with other lifestyle changes - but those are just general averages I see and certainly not scientific.

Re: Discontinuation and reinitiation of dual-labeled GLP-1 receptor agonists

#109

Post by phil21 »

rootusrootus wrote: post #70
AussieWog93 wrote: post #67

Earlier quoted context omitted.

Similar experience here with Tirzepatide. Overeating is punished swiftly and painfully. If it works for you, look into getting one of the 15mg pens and counting clicks in order to get more doses per vial. I've been on the one pen for 3 months now and it's still got plenty of juice left.

One of the quirks of buying brand name GLP1s in the US is that we don't get the dial-a-dose pens, every autopen is one-shot. Some people disassemble them to get multiple doses, but at that point you might as well get the cheaper brand name vials or go with compound or gray.

Lilly Direct sells zepbound in “single use” vials you make draws from. Very trivial to add bacteriostatic water to them and do some simple math to divide the dose. I have a few friends who do this.

You can also take apart the pens and do the same thing, but it’s a lot more involved and you’ll need to source some sterile reusable vials for it.

Re: Discontinuation and reinitiation of dual-labeled GLP-1 receptor agonists

#110

Post by amelius »

bitwize wrote: post #51
j-conn wrote: post #35

Earlier quoted context omitted.

Which do you like? Barebells salty peanut and chocolate dough over here. Though the sugar alcohols certainly aren’t great for you either, I think they were recently linked to stroke risk

Munk Pack is a good brand. They're like Kind bars but sweetened with allulose.

Thanks for the link. I also hate the sugar alcohols.

However:

> But allulose isn’t approved for use in Canada or Europe. There, it’s considered a “novel food,” which means it hasn’t been available long enough for sufficient testing, according to those governments’ standards.

> And it’s important to know that the FDA’s GRAS status doesn’t mean that allulose has been rigorously tested.

> “We don’t have studies regarding the safety of allulose at this time,” Dr. Hazen shares. “But if it follows similar trends to what we see in some other sugar substitutes that are sugar alcohols like erythritol, I would suggest there’s reason to be cautious about how much of it you consume.”

https://health.clevelandclinic.org/what-is-allulose

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