[HN Gopher] Discontinuation and reinitiation of dual-labeled GLP...
___________________________________________________________________
Discontinuation and reinitiation of dual-labeled GLP-1 receptor
agonists
Study: https://pubmed.ncbi.nlm.nih.gov/39888616/
Author : siquick
Score : 79 points
Date : 2026-03-20 21:42 UTC (1 days ago)
(HTM) web link (nautil.us)
(TXT) w3m dump (nautil.us)
| Robotbeat wrote:
| Kind of makes sense that stopping taking a drug that reduces
| heart attack and stroke risk leads to a return to the higher risk
| of before.
| ErroneousBosh wrote:
| 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.
| malfist wrote:
| Your comment is all kinds of wrong.
|
| A) it does have cardio protective effects.
|
| It does reduce your appetite, and for most people have very
| few side effects. If you get nausea you're titrating up too
| fast. Most people, because it slows gastric emptying, it
| doesn't make them shit themselves "inside and out". GLP1s are
| a decent option for treating ibs-d or bile acid issues and is
| better tolerated than your bile acid sequesterants.
|
| > You could also reduce heart attack and stroke risks by not
| eating crap and going for a walk every so often.
|
| This victim blaming advice has been given for decades and
| obesity rates have been climbing for decades. Only glp-1s
| have reduced that.
| cthalupa wrote:
| We see risk reduction for heart attack and stroke for people
| on GLP-1s even without weight loss, which belies the idea
| that the protection only comes from losing weight.
|
| Edit: In fact, from the study -
|
| BMI went from 35.86 (Continued) to 34.57 (Discontinued) to
| 35.48 (Interrupted),
|
| Heart failure percentage was 11.57% for continued use, 12.73%
| for discontinued, 11.92% for interrupted
|
| NICM went 3.10% for continued, 3.36% for discontinued, 3.31%
| for interrupted
|
| BMI was higher for the continuing users and they still had
| lower heart failure and NICM rates than the discontinued and
| interrupted groups. (Also a bunch of other things including
| stroke and heart attack but I didn't want to write all of
| these out)
| ErroneousBosh wrote:
| Have you got a link to the study those figures are actually
| from? I'm not saying their wrong but I would like to read
| and understand them for myself before I change my mind.
|
| > BMI went from 35.86 (Continued) to 34.57 (Discontinued)
| to 35.48 (Interrupted),
|
| So, what, was 35.86 the BMI at the start, 34.57 the BMI
| when they stopped taking the drug, and 35.48 after some
| interval?
|
| For someone of a fairly average height, say 1.86 metres
| (that's a little under how tall I am) a BMI of 35.86 would
| be 124kg which is ridiculously fat and 34.57 would be
| around 119.6kg so you're looking at a loss of around 4.5kg
| or so.
|
| That's a good shit and a haircut, in the grand scheme of
| things. It's fairly normal for someone's weight to
| fluctuate by a kilo up or down (a range of 2kg over normal)
| and not utterly off the map for a range of four kilos on a
| day-to-day basis, especially in obese people. That's why
| you're not supposed to keep weighing yourself and obsessing
| over the weight.
| rootusrootus wrote:
| What is it about GLP1s that bring out the kooks who suddenly
| think diet and exercise are the only valid medical treatment?
| Is it a moral issue?
| cthalupa wrote:
| As best as I can tell, people are very attached to having
| achieved their body weight through whatever means they have
| determined are valid and derive self value from it, and
| believe that GLP-1s are cheating to achieve a result they
| worked harder for.
| sublinear wrote:
| Unless we're talking about emergency care, most
| pharmaceuticals are completely unnecessary and carry
| serious risks.
|
| There's not a single qualified doctor out there that would
| promote drugs before preventative measures.
| cthalupa wrote:
| Pretty much every adult fat person has attempted diet and
| exercise to resolve their weight issue.
|
| Saying they should try this first at this point in the
| game is like having your support case escalated 5 times
| already and them saying "have you tried turning it off
| and on again"
| ErroneousBosh wrote:
| > Pretty much every adult fat person has attempted diet
| and exercise to resolve their weight issue.
|
| If it's not working for you, it may be because you
| haven't sorted the "diet" bit.
|
| Are you eating "low fat" or "low calorie" things? Because
| those are not food and they will make you fat.
|
| Eat food, just a bit less of it than you do now.
| array_key_first wrote:
| Yes, it's a moral issue.
|
| What you need to understand is there are a lot of people
| where all they have is being skinny and appearing to be
| healthy. Without that, there's nothing left for them.
|
| For a long time, there has been a moat that they can use as
| a justification for why they're better. They can say "well
| I work hard, I eat right, I put in effort!" The idea that
| others can achieve that without any of that means... well,
| they did it all for nothing. In their heads.
|
| The dirty little secret? Many of them _don 't_ do any of
| that, it's just a delusion. Always has been. I'm skinny,
| you think I go to the gym? Fuck no! I should, but I don't.
| And I eat whatever I want.
|
| But if a lot of people have to face the reality that their
| most redeeming quality is nothing of their doing, that
| would ruin them. Ruin them. They could just, like, get
| achievements or something but that's hard. Continuing the
| delusion is easy.
| shlant wrote:
| > 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??
| ErroneousBosh wrote:
| 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.
| TaupeRanger wrote:
| 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!!!"
| gpt5 wrote:
| 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.
| cthalupa wrote:
| The discontinued and paused groups in the actual study had
| lower BMI than the continuing groups - so it seems like this
| is at least partially independent of any weight regain.
|
| Which makes sense since we have strong evidence for the
| GLP-1s providing significant protective benefit even without
| weight loss.
| watermelon0 wrote:
| 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...
| gpt5 wrote:
| 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.
| techjamie wrote:
| A tale older than the use of GLP-1. People do X to lose
| weight, they hit a target weight, declare victory and
| continue the habits that got them in trouble in the first
| place. You can go a little bit heavier on the meals and
| loosen the exercise if you desire, but you still have to keep
| yourself within maintenance threshold or the weight comes
| back.
|
| GLP-1 masks the problem and people don't realize their
| actions aren't ideal once the mask is removed.
| smallnix wrote:
| It's not useless. It might be expected, but now it's more
| certain. This allows planning with it.
| esperent wrote:
| Scientifically it's valid, and good scientists and doctors
| would immediately pick up on the nuance.
|
| The issue is shameless "science" reporting like this which
| packages up the results for non experts, _without_ explaining
| the nuance because they know the sensational headlines will
| get more attention, and they _know_ non-expert readers will
| get scared and share the article on places like HN or
| Facebook.
|
| It's such an obvious play: find one doctor who'll make a
| loaded statement with the word "whiplash", write on this one
| study as if it's gospel truth, get everyone reading it as
| scared as possible. Throw in links to other emotional
| articles like " _Can you die of a broken heart?_ " throughout
| the text to trigger secondary emotional reactions that will
| get confused with the main ones. Boom, social media sharing
| heaven, who cares if the science was valid or not?
|
| And to be clear, the science underneath _might_ be valid,
| probably even is, but it would need the expertise of someone
| who understands statistics and medicine to decide whether you
| should take action based on this or not.
| ajam1507 wrote:
| The doctor using the word "whiplash" is one of the authors
| of the study.
| r-johnv wrote:
| 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.
| rayiner wrote:
| 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. Moreover, the effect of
| restarting taking the drug seems attributable to the study
| design. Those who took a break had higher risk at the end of the
| study than those who don't. But those who took a break took the
| drug for less total time than those who took it for the entire
| study.
|
| You could characterize these same facts in the opposite way.
| GLP-1s don't permanently change your body. They provide benefits
| while taking them but quickly clear out of your system when you
| stop taking them. Arguably, that's a good thing in a drug.
| IAmGraydon wrote:
| >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.
| kube-system wrote:
| 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
| conception wrote:
| Could.
| r-johnv wrote:
| Reverse the benefits != increase the net risk
|
| It took a while going through the data in the results
| section to see this.
| post-it wrote:
| It certainly does not. To make that claim, the study would
| need a control group of people who had never taken the drug.
| They didn't have that:
|
| > Participants Veterans Affairs users with type 2 diabetes
| who started treatment with GLP-1RAs (n=132 551) or
| sulfonylureas (n=201 136), followed up for three years.
| Veterans Affairs users were defined as having at least two
| visits to Veterans Affairs and having used the Veterans
| Affairs outpatient pharmacy within a year before receiving
| treatment with GLP-1RAs or sulfonylureas.
| embedding-shape wrote:
| > They didn't have that
|
| So, why not? Seems very obvious to everyone here on HN that
| it's "kind of useless" unless they did have that, yet they
| didn't. What reason would there be for ignoring that?
| post-it wrote:
| They were testing what happens when you stop taking
| Ozempic compared to what happens when you don't stop
| taking it, and also what happens when you start taking it
| again.
|
| Assembling a control group of people who have never taken
| Ozempic could be difficult. How do you control for the
| fact that people not on Ozempic are less likely to need
| Ozempic? You'd need to figure out some criteria by which
| to include and exclude patients before sorting by whether
| they take Ozempic or not, so you'd have a smaller sample
| size of people who are taking Ozempic.
|
| Best not to allow scope creep.
| ldayley wrote:
| How much of this could attributed to simply having less
| artificial hormonal support for not overeating after
| discontinuing treatment, and falling back into old habits? I'd
| love to see more research focused on these mechanisms.
| 46493168 wrote:
| In veterans with T2 diabetes:
|
| > To find out what happens when people stop taking GLP-1s, Al-
| Aly's team of researchers tracked the health of more than 333,000
| United States veterans with type 2 diabetes for three years.
| actuallyalys wrote:
| The same thing happened when the same researcher did studies on
| Covid using similar datasets. There's likely some
| generalizability but part of the reason the absolute risk is so
| high is because VA patients are a group already at high risk.
| It's partly a failure of science journalism this caveat gets
| missed but seems like it is also one Al-Aly is happy to allow.
| bethekidyouwant wrote:
| Studies get worse every year.
| jimbokun wrote:
| Or articles that try to convey the content of studies have
| always been poor and continue to be poor.
| jryio wrote:
| We finally found the first morbidity signal of GLP-1s (or lack
| thereof).
|
| These are life changing drugs, but like plastic we'll see their
| effects in force within this generation:
|
| > The longer time spent off GLP-1s, the greater the risk of major
| cardiovascular events--up to 22 percent for those who abstained
| for two years.
| stavros wrote:
| Doesn't it make sense that, if you were taking a drug that
| reduces morbidity, you'll get increased morbidity if you stop
| it?
| jryio wrote:
| Not if having a heart attack within 1 year at a higher rate
| is an co-morbidity factor when the primary treatment was for
| obesity or diabetes (not stating that obesity and heart
| disease are not positively correlated).
|
| To use a dense analogy: if I stopped brushing my teeth I
| would not expect to die of gum disease.
| malfist wrote:
| I don't think you read the study. The people returned to
| their pre treatment risk profile after ceasing treatment
| cthalupa wrote:
| You are misunderstanding the study (largely because the article
| heavily misrepresents it, would be my guess)
|
| They do not see an increase against their pre-GLP1 baseline
| risk - they see a reversal of the cardioprotective benefits the
| drug provided while they were on it.
| TaupeRanger wrote:
| You failed to understand the results of the study and quoted a
| passage that does not in any way support your assertion.
| bradleyy wrote:
| The actual study states in the summary that it's the cardiac
| protective improvement that reverses, not that you're worse off
| for having taken a GLP-1.
|
| So yeah, when you stop taking something that protects your heart
| and kidneys, it stops protecting... your heart and kidneys.
|
| There's an increasing body of work that indicates that long-term
| GLP use (initially higher doses for weight loss, then tapering
| down) retains the cardiac and kidney benefits and can actually
| lead to additional weight loss.
| nisegami wrote:
| This makes it even more fantastic that the supply of GLP1s from
| my country's only legal importer is spotty and I've been suddenly
| cut off twice already
| rootusrootus wrote:
| One benefit of going gray is that you can stock up. If I could
| not get any more, it would be a number of years before I ran
| out.
| 0x3f wrote:
| Others have addressed the clickbait nature of the title
|
| I'm just surprised the food industry or whoever is willing to
| fund FUD content that ostensibly has such an indirect effect on
| their bottom line.
|
| Although I guess they spend a ton on ads which are also of
| dubious value, so maybe it's to be expected.
| Aboutplants wrote:
| Also News I guess - People who pick up smoking again after a
| period of cessation, regain all negative effects of smoking that
| they previously experienced during that past smoking periods,
| eliminating the positive effects of the smoking cessation.
| Aboutplants wrote:
| The most capitalistic drug ever! Take the drug forever and lose
| weight but stop taking it and you'll die.
| devin wrote:
| That isn't what this says at all.
| mh- wrote:
| _(off-topic, but since the thread already is..)_
|
| HN felt like one of the last places on the internet I could
| have good-faith conversations with intelligent people who
| would form thoughtful, on-topic replies.
|
| And now it feels like the user base here has shifted enough
| that the voting system no longer consistently elevates the
| interesting comments, but the comments that reinforce
| people's worldviews.
| TaupeRanger wrote:
| What do you mean? All of the comments that misunderstand
| the study are downvoted from what I see.
| arjie wrote:
| Everyone feels Eternal September sooner or later. I
| recommend blocking users on this site. Having hit about 800
| or so blocks I find that the conversation quality has
| skyrocketed. You still get one or two low quality users on
| a thread like this (I hadn't blocked this guy) but the
| truth is that it's usually a few people.
|
| Any time a user gives me a flash of annoyance with a
| nonsensical comment that's the last time I see them. This
| isn't a native feature but Claude will implement it for you
| in a really short amount of time. If you want a feature set
| to copy or a list of users to seed, you can just copy mine
| (in profile).
| mh- wrote:
| Yeah, unfortunate that it's come to that, but I think
| you're right.
|
| I started to write a comment about having some
| (additional) ideas for a Chrome extension, clicked your
| profile, watched the YouTube video. Fantastic. I think it
| already does everything I wanted.
|
| Thank you for making and open sourcing this!
| rootusrootus wrote:
| Everyone feels this way about HN at some point, it is
| normal. It is probably true that the user base has grown
| and so you see more low-value comments in absolute numbers
| as time goes on, but I still think the overall quality is
| decent and the community moderation solid.
|
| It is also a Friday afternoon, and HN's weekend (and to
| some extent overnight) 'personality' is noticeably
| different than during typical business hours. I enjoy
| coming here on weekends but it gets a bit more wacky.
| Teknoman117 wrote:
| 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 you've got mental health
| struggles that feed into your eating patterns, GLP-1s might not
| help with your weight problems.
| bradleyy wrote:
| Hey, I can identify. Sending good thoughts your way.
| cthalupa wrote:
| That's unfortunate! It might be worth checking out Tirzepatide
| or Retatrutide once it is released. The GIP and Glucagon
| receptors might be better targets for you, even if the GLP-1
| receptor seems to not help.
| pitched wrote:
| 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.
| phil21 wrote:
| 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.
| brap wrote:
| Wegovy/Ozempic didn't do anything for me for months. Then my
| doc put me on Tirzepatide+Phentermine combo and I forgot what
| being hungry even feels like.
| bobsmooth wrote:
| How long have you been on Phentermine? For me it stopped
| working after only a couple weeks.
| vladgur wrote:
| Do you have to remind yourself to consume things like
| proteins, etc to prevent muscle loss?
| cthalupa wrote:
| I couldn't hit my macros on tirzepatide - couldn't get
| enough protein without feeling sick to my stomach. One of
| the reasons I swapped to reta.
|
| (though as a general note for anyone reading, just getting
| enough protein isn't enough - you need muscle stimulus too.
| Getting enough protein will help reduce the amount lost but
| if you really want to stop it, you gotta do resistance
| training)
| amelius wrote:
| Did you try those zero-sugar candy bars (often labeled as
| protein bars)? They work quite well for me, no messing with
| GLP-1 necessary.
| j-conn wrote:
| 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
| bitwize wrote:
| Munk Pack is a good brand. They're like Kind bars but
| sweetened with allulose.
| amelius wrote:
| 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
| bitwize wrote:
| I don't consume more than like a few grams per day to
| sweeten things like coffee, as well as the 5g or so in a
| single Munk bar. I seem to tolerate it well.
| amelius wrote:
| I'm a Barebells Coco Choco "fan", though I'm aware of the
| stories around sugar alcohols. I think those bars are way
| too sweet anyway. They could use far less sweeteners. Would
| love to hear about more responsible options.
| 01100011 wrote:
| It lets me more or less skip a meal but holy hell I am craving
| sugar more than ever. On the whole I'm cutting calories and
| have lost a lot of weight, I just wish I didn't want sugar this
| much.
| Teknoman117 wrote:
| I've always been more of a savory kind of person myself. I'd
| take biscuits and gravy or a steak over sweets any day!
|
| But I feel you on sugar. Took me a long time to cut sugar
| cravings. A decade ago I cut _regular_ soda out of my diet,
| which a few years later led to me cutting out pretty much
| anything sweetened. Realistically it wasn't the sweetness for
| me, it was the "mouthfeel" or doing something with your
| mouth. Just straight sparkling water satisfied the entire
| craving for me.
|
| The hardest thing for me to give up / heavily cut back on was
| fried things. Maybe that's the result of my parents using
| french fries as the reward food when I was a kid...
| bitwize wrote:
| Try allulose-sweetened stuff. Allulose is a sugar your body
| doesn't metabolize like sucrose. It has zero calories and
| does not increase your blood sugar. It's a component of maple
| syrup and so does taste a bit maple-y, but better than most
| artificial sweeteners and even stevia leaf extract (stevia
| and aspartame have a "tang" to them I dislike).
| rootusrootus wrote:
| You missed out on both of the weight suppression tricks, which
| really does suck. Appetite suppression (or reduction of food
| noise) is pretty useful, but GLP1s also tend to punish you
| mightily if you overeat. For me, even if I were hungry,
| overeating will make me hurt for hours. I could not gain weight
| on this even if I _wanted_ to.
|
| There are some difference, too, between the various drugs. I
| never tried ozempic, I went directly to tirzepatide (zepbound).
| And then to retatrutide. I will say that reta is in some ways
| the most interesting, because it has less appetite suppressing
| activity than tirzepatide (this is common, not just me), but it
| still cuts my stomach capacity quite a lot, and ramps up my
| metabolism. I had stalled at about 90 pounds down with
| tirzepatide, and reta immediately knocked off another 15. I
| track calories, and I had changed nothing. Felt more hungry,
| still lost more weight. Wild.
|
| From one rando to another, I recommend trying tirzepatide. Or
| try semaglutide again but stacked with cagrilintide -- some
| people get pretty great results with that, similar to tirz.
| Teknoman117 wrote:
| Yeah I might just have to go get it out of plan. Kaiser
| covers Ozempic, but none of the Tirzepatide based
| medications. (Edit: looks like that might have changed)
|
| I am a big guy (6'4, 330 lbs), but I was amazed that Ozempic
| just seemed to do nothing. I was having the gastric side
| effects, but I could still eat 3000 calories a day if I
| cheated without feeling anything.
| gedy wrote:
| I highly recommend Zepbound, you might try it.
| AussieWog93 wrote:
| 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.
| rootusrootus wrote:
| 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.
| Teknoman117 wrote:
| When I was on Ozempic in the US (Bay Area), it was a
| dial-a-dose Ozempic branded pen. Came with 4-6 single use
| needles you'd screw onto the end before use, and discard
| into a sharps bin after.
| phil21 wrote:
| 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.
| sublinear wrote:
| I went down from 390lbs to 240lbs gradually over 5 years. I
| have maintained a weight of 240lbs since then (6'1" tall).
|
| The first year was the most dramatic loss of 100lbs. I was
| miserable and didn't know what I was doing other than counting
| calories. The rest of it was more considerate of total
| nutrition, and that's what made my good eating habits stick.
|
| I say this because while I'm not a doctor I think GLP-1 is
| probably unnecessary for the vast majority of patients. Better
| food and information is more available than ever before.
|
| I would strongly advise to watch your A1C and get out of the
| diabetes danger zone if you are. Most people can drop a few
| percent in as little as 6 months and it makes a massive
| difference in mental health. Blood glucose has a direct impact
| on the brain and overall cardiovascular health. If you drink
| alcohol, you might want to take a break also to let your
| liver/kidneys/pancreas do their jobs properly and restore
| insulin sensitivity and other hormones. Look into the "fruit
| paradox", and more generally get a good salad in for lunch to
| address nutrient deficiencies. Not crappy salads either. You're
| not a rabbit. Treat them like the amazing sandwiches without
| bread that they are.
|
| Sounds like old advice, because it is, but I find people aren't
| listening because they want to more deeply understand why to do
| it and what the effects are. Convenience and unintuitive
| pricing are false bargains that get in the way of healthier
| habits. Focus on nutrition and not quantity. Change your
| groceries, change your life.
| rootusrootus wrote:
| > I say this because while I'm not a doctor I think GLP-1 is
| probably unnecessary for the vast majority of patients.
|
| We have mountains of evidence that willpower fails for
| something like 99% of everyone, which is far from a vast
| majority. I applaud anyone's efforts to become healthier,
| however (though 240 at 6'1" is still obese, I would still
| explore medicine if I could not get any lower "naturally").
| sublinear wrote:
| Thanks for the reply. Your perspective framing this as
| "willpower" is precisely what I'm concerned about.
|
| I didn't need any willpower to do this and I'm not even
| humblebragging nor think of myself as a tough guy. I'm
| saying that healthy habits are simply a matter of
| understanding. If someone wants to take GLP-1 on top of
| that, it's their call. Many seem to be under the impression
| it's so vital for their specific situation to lose weight
| or avoid a heart attack and I think that's plainly false.
| We shouldn't be feeding fear, and humans aren't that
| unique.
|
| I did not change my diet. If anything I just added more
| variety with a specific intent and it worked. Even just
| changing the order in which one eats things (fiber before
| sugary foods) can make a big difference. Once I got the
| blood glucose under control all the strong cravings and
| eating mistakes basically went away on their own without my
| conscious effort. The body is all connected and driven by
| hormones.
| cthalupa wrote:
| > I'm saying that healthy habits are simply a matter of
| understanding.
|
| Plenty of people have heard everything there is to hear
| on this, understand it, and still fail to implement it.
|
| > I did not change my diet.
|
| You plainly did. You do not lose weight without your diet
| changing.
|
| > If anything I just added more variety with a specific
| intent and it worked.
|
| This is changing your diet.
|
| > Even just changing the order in which one eats things
| (fiber before sugary foods) can make a big difference
|
| Changing your diet to eat more filling foods is a very
| frequently recommended thing, yes.
|
| > Once I got the blood glucose under control all the
| strong cravings and eating mistakes basically went away
| on their own without my conscious effort.
|
| My blood glucose has always been excellent. It did not
| stop me from having food noise and cravings.
| sublinear wrote:
| 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 existing recipes. Why force
| nasty carrots onto the plate when I can eat spinach,
| cantaloupe, pumpkin, sweet potato, etc.?
|
| I guess I also didn't emphasize enough that I took things
| super slowly? Taking 5 years to do what I did is a really
| modest goal. I just wanted to manage risk with minimal
| change. This is the pareto principle in action.
|
| If we're really going to argue over stats, the effects of
| GLP-1 is meaningless noise in comparison and probably way
| harder to commit to. I just wanted to eat good and not
| feel like shit all the time. Isn't that what everyone
| wants? What if instead of there being "one weird trick"
| or a "miracle drug", we consider that basic nutrition is
| simply misunderstood and full of _hundreds of weird
| tricks_ that are proportionally much easier to implement
| and they 're damn tasty too?
| cthalupa wrote:
| 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 the _overwhelming_ majority of
| people that are obese and go on GLP-1s have tried other
| interventions before and failed at them. ~70% of all
| obese people have tried to lose weight in general, ~50%
| have recurring attempts, and while I don 't have stats to
| back it up I am confident that the sort of people who are
| willing to go and inject themselves every week are the
| sort of people that have tried to lose weight in other
| ways.
|
| > probably way harder to commit to.
|
| A subcutaneous injection once a week is nothing. Dealing
| with constant food noise? I could maintain that if the
| rest of my life was stress free, and that's how I would
| drop 30lb. Once stress came back? So did the weight.
| Because for me, rearranging food doesn't matter if I
| still can't stop thinking about it even if I'm not
| actually hungry.
|
| I'm on reta. It does barely anything to suppress my
| appetite - physical hunger has never been my issue. And I
| can easily eat however much I want - most days I am below
| 2k calories, but Saturday was an annual event with
| friends and I'm sure between food and alcohol I was
| probably at 5k calories for the day. But what reta does,
| is absolutely murders my food noise. I don't think about
| food constantly. I don't go eat because I got bored. The
| only thing I have to commit to for it is, once a week,
| put a needle on my injector pen, twist the dial to the
| right dosage, poke it into a spot where I still have
| subcutaneous fat, depress the twist top. Once a month I
| reconstitute a new vial.
| walletdrainer wrote:
| > 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.
| jakevoytko wrote:
| My doctor, who is on the older side, told me that he went
| through his records when GLP-1s started being prescribed
| for weight loss. He wanted to calculate what percentage of
| his patients (a) he had advised to lose weight, (b) reduced
| their weight to healthy levels, (c) and kept it off.
|
| From the starting population of overweight people, only 3%
| of people dropped down to, and stayed, a healthy weight.
| rjurney wrote:
| So try Mounjaro. It works better.
| tsoukase wrote:
| Try Fluoxetine 20mg, first 1 per day, later 2. Glp-1 doesn't
| work in stress related obesity.
| mullingitover wrote:
| I mostly feel bad for job losses due to AI, but I won't shed a
| tear for journalists who make a living spreading misinformation
| about the results of research.
|
| > They found that the risk of heart attack and stroke _jumped_ in
| those that paused GLP-1 treatments for as little as six months,
| compared to those who continued taking the medication.
|
| (Emphasis mine) The 'jumped' would more correctly say 'tended to
| revert to baseline' if you just had a basic LLM summarize this
| study for you...but then that wouldn't drive clicks and shares on
| your article.
| amazingamazing wrote:
| Honestly don't understand it. Feels like a lack of discipline. I
| was 250. Plugged in a bunch of numbers into an app and it gave me
| a calorie count per day. I brought a scale with me everywhere,
| used ChatGPT to guesstimate calories, I added 50% for good
| measure. A year later I'm 175. You can't do this even with drugs
| you're gonna get fat anyway.
|
| I'm most curious about someone like me vs someone who lost the
| same amount on glp1 with respect to these stats
| rootusrootus wrote:
| We know that GLP1s have benefits that are disproportionate with
| just weight loss, so someone who is otherwise like you in terms
| of weight loss would probably have better cardiovascular
| markers.
|
| Probably the biggest difference, though, is that an average
| "you" will be back at original weight, plus a little, in about
| a year, while the average GLP1 user will (assuming they keep
| taking it) be the same weight, or even a bit lighter.
| renewiltord wrote:
| Everything is discipline. If you just always do the thing
| you're supposed to you will win at life. People can't always do
| the thing they're supposed to so they supplement with drugs
| that help them do it: caffeine, amphetamine, SSRIs, GLP-1RAs
| and related drugs.
|
| In fact, everything is discipline. If you were disciplined
| enough to always put the basketball in the net from anywhere on
| the court you'd be Steph Curry. The thing is most people don't
| have that kind of discipline. Someone runs up to them and puts
| their hand up in the air? They shoot wide or balk. Curry shoots
| true. Discipline.
|
| Just always do the right thing and never do the wrong thing and
| you'll be fine at literally everything.
| amazingamazing wrote:
| Some things require talent like your examples, weight loss
| does not imho. The disparities in obesity and culture within
| country says it all.
| cthalupa wrote:
| The ability to be disciplined about eating is also a
| talent.
|
| Or do you think that somehow genetics don't play one of the
| largest roles in your ability to be disciplined when it
| comes to food?
| amazingamazing wrote:
| If you can be disciplined about taking a drug you can
| about food. How do you explain correlations in obesity
| across cultures? Genetic superiority? Again, imho just
| making excuses for laziness. The same logic you're
| applying here also applies to even taking the drug and
| picking up refills from the mail...
|
| Also look at obesity rates across time within the same
| country. It's clearly not an issue of discipline, it's an
| issue of what's being eaten.
| cthalupa wrote:
| Why in the world do you think that taking a once a week
| injection requires even remotely similar levels of
| discipline to dealing with daily hunger and food noise?
| There's like, a dozen orders of magnitude in between.
| This is a silly argument.
|
| > How do you explain correlations in obesity across
| cultures? Genetic superiority?
|
| Every developed nation in the world except Japan has been
| seeing obesity and overweight rates rising at significant
| rates, including countries that have fairly similar
| cultures, such as Korea. You also see people move to
| America and stay in relatively isolated pockets of their
| culture and still gain weight.
|
| So no. It's a matter of access to hyper palatable calorie
| dense food. The more of it around, the more likely people
| are to get fat. The fatter you get, the more of a
| feedback loop you end up in for a wide variety of known
| and relatively well understood mechanisms. GLP-1s help
| short circuit that feedback loop.
| amazingamazing wrote:
| > It's a matter of access to hyper palatable calorie
| dense food. The more of it around, the more likely people
| are to get fat.
|
| Now there's something we agree on. If only we could agree
| that no one is stuffing cheeseburgers down people's
| throat other than themselves. So close.
|
| Once the shame around disgusting fattening food has
| reached a critical mass the problem will solve it self.
|
| Ironically the excuses you make for them only worsen the
| issue. If fat people and the food they ate were
| appropriate shamed they both would cease.
|
| FYI in Japan fat people are ruthlessly bullied. Fat
| people are rare. Food for thought, pun intended.
|
| Stop tolerated junk.
| cthalupa wrote:
| > Now there's something we agree on. If only we could
| agree that no one is stuffing cheeseburgers down people's
| throat other than themselves. So close.
|
| No one is saying that it is forced. What I am saying is
| that your sense of moral superiority for the fact you
| aren't is misplaced.
|
| Let's give you an anecdote: Up until 18 or so, I was a
| stick. I went from being a stick to getting into
| powerlifting. I spent the first chunk of my 20s with a
| pretty great physique. Then as I had more and more
| responsibilities in life, I had less and less bandwidth
| to apply to things like cooking, exercise, etc. I slowly
| lost muscle mass. I slowly gained fat. I had never had
| food noise when I was skinny - I had never compulsively
| felt the need to eat, regardless of hunger. I had never
| had food just constantly occupy my brain. After my slow
| descent into obesity, something fundamental about my
| relationship with food had changed. When my stress was
| lower and I was skinny or later fit, staying that way was
| easy. It didn't require great mental fortitude, massive
| discipline, any of that. And when I got fat, it wasn't
| because I was craving food - it was because I had shit to
| do and couldn't take the time to cook. Or because I was
| going outwith friends or my SO and eating out was a huge
| part of my social life.
|
| When I looked at myself and decided I had to change, I
| though I just needed to stop doing those things. Stop
| going out, force myself to take the time to cook and let
| other things fall on the backburner, etc. Except now I
| thought about and craved food in a way I never had
| before. I went from thinking exactly the same as you to
| realizing 'Oh shit. This wasn't as simple as I thought it
| was.'
|
| I lost weight plenty of times. Significant weight - not
| just a few lb, but 30+. Multiple times. And then I'd get
| busy at work, I'd have family members going through
| problems and need help, I'd have a rough patch with an SO
| - as soon as my mental bandwidth got divided, the weight
| loss stopped and regain started.
|
| Even if an individual is just always able to resist, it's
| almost entirely based on their genetics. If you want to
| feel superior because of something you had no control
| over, I guess that's your perogative.
|
| > Once the shame around disgusting fattening food has
| reached a critical mass the problem will solve it self.
|
| I think shame is a useful human emotion. We evolved it
| for a reason. But we also know that it has limits and
| that once those are reached more shame on top, it becomes
| counter productive.
|
| > Ironically the excuses you make for them only worsen
| the issue. If fat people and the food they ate were
| appropriate shamed they both would cease.
|
| No. Fat people experience plenty of shame, and for a huge
| amount of them, it only worsens the problem. Once you
| shame a person too much - once you make it about them and
| not about the action - they start to feel that they are
| unable to make a change because they have less worth than
| those people that can, and often end up losing even more
| control in their relationship with food or whatever else
| they are being shamed about.
|
| > FYI in Japan fat people are ruthlessly bullied. Fat
| people are rare. Food for thought, pun intended.
|
| This is not universally true - it is highly regional,
| though the most populated portion of Japan is definitely
| an area where this is largely the case. But even in areas
| where this is not the case, they still have significantly
| lower obesity rates. Osaka and Hokkaido are significantly
| more laid back about it than the Tokyo area, for example,
| but they still have relatively flat obesity rates.
|
| Basically every fat person in the developed world
| receives more than the maximum effective dose of shame
| over their body and it hasn't made them stop being fat.
| renewiltord wrote:
| You just have to be disciplined to always shoot accurately
| at the basket. Most people send it one way or the other but
| if you are disciplined enough in your aim at the basket no
| matter the constraints you will be the best basketballer of
| all time.
| array_key_first wrote:
| Weight loss of course is helped by talent, because genetics
| are talent.
|
| Metabolisms fluctuate, although granted not by much. But
| what _really_ varies is your response to food. And it 's
| not just genetics. It's food scarcity, early childhood,
| your environment.
|
| The (maybe) sad reality is that there will be people
| skinnier than you will ever be who have put in zero effort.
| Nada. That's life. Just like there's people who can sing
| better than me off the rip and I took vocal lessons for 10
| years. Life's not fair.
|
| But the bright side is, I can drink and not be an
| alcoholic. Maybe they're just lazy or something. Or, maybe
| this mentality is one people feed themselves (ha) to feel
| better about the circumstances of their life.
|
| Wouldn't we all like to believe we're the way we are
| because we're strong, brave, and hard-working?
| AussieWog93 wrote:
| I'll bite!
|
| A decade or so ago, when I was still in uni, I managed to get
| similar results naturally too - ~100kg down to ~65kg in around
| 18-24 months just by eating healthy and exercising more.
|
| I put back all of that weight and then some during the COVID
| pandemic (I'm in Melbourne, Australia - we had the worst
| lockdowns on planet Earth) and this time struggled for years to
| lose it until trying GLP-1 drugs a few months back.
|
| For me, what made it harder the second time around wasn't so
| much of a difference in discipline skills (if anything, they've
| improved) but the fact that there was so much more going on in
| my life - young family constantly getting sick, small business
| that started struggling, relationship/social issues, health
| issues (sleep apnoea) etc. etc.
|
| I'd get on the weight loss train, lose a couple of kilos, then
| the whole family would get sick with the flu and I'd put it all
| back on again while recovering. Or maybe I'd be forced to shift
| my focus to the business so that we could keep the lights on.
| Or any number of things.
|
| I guess my point is that it's not difficult to lose weight
| naturally (or any self-improvement, really) in and on itself,
| but it's completely different ballgame when you're fighting a
| war on 6 different fronts. Having one of those problems simply
| just disappear through GLP-1 drugs genuinely feels like a
| miracle.
| storus wrote:
| Isn't GLP-1 creating a "feel-good" starvation? Patching the
| receptors telling the brain one is not hungry and then just
| letting the body starve happily, leading to significant muscle
| loss and aged face? Contrary to e.g. water fast where the body
| switches to 100% ketosis that can run as long as there is any fat
| in the body and one supplements electrolytes (Mg/K/P/HCO3) and
| vitamins (predominantly B1/B2/B3), leading to a much more healthy
| appearance?
| mrtesthah wrote:
| There is nothing inherent in your description that would
| support your implied claim about facial aging.
| storus wrote:
| "Emerging research suggests GLP-1 receptors are present on
| adipocytes and fibroblasts. Some animal studies indicate that
| GLP-1 agonism may promote lipolysis in subcutaneous fat more
| aggressively than in visceral fat, leading to
| disproportionate loss of facial fat. It also may affect
| collagen synthesis or skin architecture, though human data
| are still evolving."
| rootusrootus wrote:
| GLP1s do not themselves cause any worse muscle loss than you
| would experience if you lost the weight by watching calories
| the old fashioned way.
|
| "Ozempic face" is almost certainly an artifact of people who
| spent their life significantly overweight having somewhat
| looser skin than they would if they had maintained a low weight
| throughout their life.
|
| Also, not everyone gets the face effect, not by a long shot.
| gedy wrote:
| Yeah exactly, what people call Ozempic Face is often just
| wrinkles. I look a bit older now that I lost 40 lbs, but much
| healthier shape. Fat does fill in your face some
| storus wrote:
| Not really, Ozempic face is the same face as one gets when
| starved of food for a longer period of time from low caloric
| diet that contains carbs. Ketosis on the other hand doesn't
| cause this unless one has almost no fat left as it doesn't
| switch body to the starvation mode.
|
| There are two modes the human body operates normally -
| insulin-driven, active when carbs are in the food, and
| ketone-driven, active when there is a lot of fat storage and
| no food intake, or food has no carbs. Insulin-driven
| operation switches to starvation when food intake has caloric
| deficit but still enough carbs for insulin to be triggered;
| ketones on the other hand lead to zero insulin activity and
| pure fat burning; starvation is only activated when humans
| reach around 4% body fat while in ketosis.
| cthalupa wrote:
| This is a bunch of pseudoscience.
|
| "Starvation mode" as people talk about it is generally
| nonsense - the exceedingly low bodyfat you mention for keto
| is the same place you would see it in a non-keto diet when
| we talk about actual starvation mode and not whatever
| you're talking about with a non-ketogenic diet.
|
| The only real difference when it comes to the biology here
| is that fat mobilization into glucose is significantly
| slower and less efficient, which keeps your blood sugar
| levels more constant, which results in fewer post-meal food
| cravings. Which isn't nothing, but it's not muscle sparing
| in and of itself.
|
| We have plenty of studies here. Keto diets are not better
| for sparing lbm.
|
| https://pubmed.ncbi.nlm.nih.gov/38934469/
|
| In fact, if you already have significant muscle mass, it
| might be worse. Glycogen is hugely important when doing
| resistance training, and keto significantly impacts your
| glycogen stores. People perform worse with their resistance
| training on keto than regular diets.
|
| https://pmc.ncbi.nlm.nih.gov/articles/PMC9244428/
| https://pmc.ncbi.nlm.nih.gov/articles/PMC8469041/
| storus wrote:
| I suspect you have no idea that your body has two
| independent energetic circuits - one driven by insulin
| and glucose, the other driver by ketones. Just please
| dump this to any decent LLm to give you ELI5. Muscles
| obviously need glucose for their best performance which
| is why strength training is not recommended during
| ketosis; OTOH ketosis is naturally muscle-sparing.
| cthalupa wrote:
| > I suspect you have no idea that your body has two
| independent energetic circuits - one driven by insulin
| and glucose, the other driver by ketones.
|
| I am fully aware - I have spent several years of my life
| following a ketogenic diet. None of that is relevant for
| "starvation mode" and insulin within that context. I was
| replying to your specific points - not providing an
| explanation on how ketosis works from end to end.
|
| Unless you are claiming that your body just doesn't
| produce glucose/glycogen and insulin when in ketosis?
| Which would also be incorrect.
|
| > Muscles obviously need glucose for their best
| performance which is why strength training is not
| recommended during ketosis;
|
| Strength training should 100% still be done in
| ketosis/while following a ketogenic diet. It will be
| suboptimal compared to a regular training, but being in
| ketosis doesn't magically make resistance training
| optional if you want to be healthy.
|
| > OTOH ketosis is naturally muscle-sparing.
|
| It is not and the study links in my post show consistent
| data here. There might be an exception if you are an
| endurance athlete but that is based on far more limited
| data than the rest of the research. So... if you're a
| high level endurance athlete that is also somehow fat,
| keto might be a better option when it comes to sparing
| muscle, but for the rest of us, not the case.
| storus wrote:
| You keep mixing normal carbohydrate metabolism with
| functional starvation mode when in low caloric high carb
| diet, i.e. elevated insulin in a low-energy/tired mode
| with increased cortisol, ramping up gluconeogenesis from
| muscle tissue, catabolic state from elevated stress
| hormones, T3 thyroid hormone underproduction, adrenaline
| spikes leading to insulin resistance beta-andregenic
| sensitivity downregulation, none of which is present in
| ketosis from e.g. water fasting.
|
| As for ketosis sparing muscles that comes from a wide
| range of effects like low insulin, preserved/increased
| GH/IGF-1, BHB-inhibited muscle proteolysis and low
| leucine oxidation.
|
| https://pubmed.ncbi.nlm.nih.gov/41035089/
|
| Your super confident attitude is likely going to lead
| nowhere for any people following your advice and when
| they confront you about not reaching any fat loss goals,
| your response will be likely "it's you", instead of
| understanding the gaps in your own knowledge.
| cthalupa wrote:
| Muscle loss is determined by your protein intake, muscle
| stimulus, and rate of weight loss. Plenty of people start
| lifting for the first time (or after having stopped for
| extended periods of time) when going on GLP-1s and actually put
| on muscle mass.
|
| It might result in more loss of buccal fat than otherwise but
| even that is not definitive. Activating the receptors is not
| the same as burning fat - there are GLP-1 receptors all over
| your body in all sorts of organs. If you activate them in your
| brain you're not burning your brain for energy.
| warmedcookie wrote:
| n=1, been lifting weights for 25 years and lost 40 lbs on
| Zepbound and counting.
|
| I can still do my routines easily with no issues. My muscles
| look slightly smaller I think, but maybe that's the fat
| around them that's been diminished.
| r-johnv wrote:
| This is the study that the article references. (The linked one on
| the post is an older study)
|
| https://bmjmedicine.bmj.com/content/5/1/e002150
| jeremie_strand wrote:
| The same patern plays out with statins and antihypertensives --
| discontinuation events are well documented. The real question is
| whether we frame GLP-1s as a treatment 'course' or a maintenance
| medication, and the medical system seems largely unprepared for
| the latter.
| camillomiller wrote:
| We built a world where food is so processed and toxic that it
| makes you easily fat, but instead of fixing that we invented a
| drug that makes you eat less. Why not invent a drug that makes
| you less thirsty for those whose water is contaminated by
| fracking?
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