[HN Gopher] GLP-1 therapeutics: Their emerging role in alcohol a...
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       GLP-1 therapeutics: Their emerging role in alcohol and substance
       use disorders
        
       Author : PaulHoule
       Score  : 119 points
       Date   : 2025-10-28 02:00 UTC (1 days ago)
        
 (HTM) web link (academic.oup.com)
 (TXT) w3m dump (academic.oup.com)
        
       | t-writescode wrote:
       | Technology and discovery are so cool.
       | 
       | One breakthrough and then a WHOLE BUNCH OF NEW STUFF happens all
       | at once now that this new idea or new pathway is created.
       | 
       | mRNA vaccines break away and now they're testing them in
       | everything. GLP-1 showing signs of use in obesity and now it's
       | being tested for a whole gamut of other things. All very
       | exciting!
        
         | fullshark wrote:
         | This was the framing behind James Burke's Connections if I
         | recall, a wonderful documentary series.
        
       | tracker1 wrote:
       | All I will say, is if/when you start noticing digestive issues,
       | it's probably the GLP-1 even if it's after a year of taking the
       | stuff... and woah boy, coming off the stuff is anything but fun.
        
         | tanvach wrote:
         | How so? Can you describe more of your experience if you don't
         | mind sharing?
        
           | tracker1 wrote:
           | Started developing gastroparesis issues after about a year on
           | Trulicity... over the pandemic, due to shortages I was
           | switched to Ozempic for a few months which was less effective
           | with my diabetes mgt. I didn't actually lose weight on the
           | medication(s).
           | 
           | After seeing several doctors about the issue including a
           | couple specialists, only one of about half a dozen
           | medications tried actually worked to help the gastro issues,
           | which included fecal vomiting, rotted fermented food coming
           | up, both regularly. No actual blockages. The medication that
           | did work wasn't covered by my insurance. After a couple years
           | of suffering, I saw a news report about the Trulicity lawsuit
           | related to gastroparesis issues. Over the same period, I
           | started to develop retina issues, several retina bleeds and
           | regular injections to treat it.
           | 
           | When I found out about the lawsuit, I stopped taking the
           | medication going back to straight insulin injections (long
           | and short) currently Lantis and Novalog. For close to a year
           | after coming off, I experienced a feeling of starvation
           | 24/8... didn't matter if I was physically full up to my
           | throat, the ravenous feeling of hunger would not subside. I
           | gained about 80# during this time (again, didn't lose weight
           | on the meds).
           | 
           | I'm a few years off and my digestion is inconsistent and
           | unpredictable... sometimes I'll have a few days where things
           | flow normally... others I'll be backed up for close to a week
           | and have to take a heavy magnesium laxative to get things
           | going again. I stay pretty close to carnivore as just about
           | anything else can range from discomfort to pain. Not to
           | mention legume allergies and really sensitive to wheat... I
           | still cheat about once every other week, and I pay for it
           | physically.
           | 
           | Because I was on more than the one medication, I cannot
           | participate in either the Trulicity or the Ozempic class
           | action lawsuits. These medications have kind of ruined my
           | life. I'm now about half blind and using 45" monitors to
           | work, and even then have to zoom text and lean in to be able
           | to function.
           | 
           | Over the years, I've been on several drugs for diabetes that
           | I'd built up a quick tolerance to, that may have had other
           | negative effects... Byetta, Victoza and others... I've always
           | had digestion sensitivities, these just turned it up to 11.
           | When I started Trulicity, my insulin use was pretty minimal
           | and I was already on a Keto diet and had been losing
           | weight... I wish I'd stuck with that and never even heard of
           | the stuff.
           | 
           | Some of the recollections are a bit jumbled, apologies for
           | that, I'm just kind of writing as it comes to mind.
           | 
           | Aside: along with the medical issues has been some employment
           | inconsistencies the past few years with a few contract roles
           | spread a few months apart. I had hoped to maintain my income
           | level as many available jobs were lower pay. Currently, my
           | insurance is "emergency" coverage based, and doesn't even
           | cover the 3 doctors I'm seeing regularly and doesn't help
           | much with the medications I am still taking. Let alone the
           | eye injections I haven't been able to get for about a year
           | now ($7k/eye/injection). Tried working 2 jobs for a while,
           | but couldn't keep up with the load after a few months. I'm
           | depressed and angry. Prior to about 8 years ago, I never
           | carried debt... now I'm maxed out and staring at bankruptcy.
        
             | ArnoVW wrote:
             | That sounds pretty awful. Hang in there. Hope you have a
             | support network of sorts and find a way out.
        
             | ogogmad wrote:
             | Holy crap, I'm sharing this. Hang in there.
        
         | titanomachy wrote:
         | What was your comedown like? After 6 months of taking
         | subcutaneous semaglutide, I just stopped taking it one day and
         | it was fine. Need a bit more effort to be mindful of snacking
         | now, though.
         | 
         | EDIT: saw your other comment that you felt you were starving.
         | that sucks. the whole thing experience sounds awful.
        
       | sghiassy wrote:
       | As an alcohol enthusiast on 12.5mg of Zepbound for the last
       | several months, my ethanol consumption hasn't diminished much
        
         | sghiassy wrote:
         | I can also add I have little to zero side effects from Zepboubd
         | if that adds anything
        
         | bluescrn wrote:
         | As a beer enthusiast drinking unhealthy amounts rather too
         | frequently, my drinking went _way_ down when on Mounjaro.
         | 
         | (Maybe it wouldn't have made the same difference if I was into
         | whisky instead of beer - with beer, I suspect it's the
         | relatively large volume of drink involved that may have made it
         | less appealing?)
         | 
         | Recently switched to Wegovy since the big Mounjaro price hikes
         | here in the UK, and it seems rather less effective overall.
         | Both beer and snacks are somewhat more appealing again :(
        
       | dynm wrote:
       | > A more recent RCT showed that low-dose semaglutide reduced
       | laboratory alcohol self-administration, as well as drinks per
       | drinking days and craving, in people with AUD [72].
       | 
       | I think this quote is... wrong? Or at least extremely misleading?
       | Here, citation 72 refers to a paper by Henderson et al. That
       | paper did (sorta) reduced laboratory alcohol self-administration,
       | but did _not_ find _any_ reduction in the amount that people
       | drank. https://dynomight.net/glp-1/
        
         | dynm wrote:
         | OK looking at the original abstract:
         | 
         | > Semaglutide treatment did not affect average drinks per
         | calendar day or number of drinking days, but significantly
         | reduced drinks per drinking day (b, -0.41; 95% CI, -0.73 to
         | -0.09; P = .04)
         | 
         | So they didn't find any reduction in (1) drinking, or (2) in
         | the number of days that people drank, but they did technically
         | find (3) a reduction in the number of drinks that people
         | consumed on the days that they drank. So I guess what they said
         | is technically correct... but I still think it's very odd not
         | to mention the headline result that there was no actual
         | reduction in _drinking_!
        
           | wrs wrote:
           | I don't understand the math here. The average per calendar
           | day didn't go down, so the total drinking is the same. That
           | total is distributed among the drinking days, which are also
           | the same. So how can the drinks per drinking day have
           | changed?
        
       | hbosch wrote:
       | Much has been said about the GLP drugs and their interactions
       | with all kinds of addictive disorders. Alcohol, drugs, even
       | gambling... Anecdotally, I "struggled" at times with gaming (not
       | joking). I would find myself skipping meetings at times or
       | ducking away to play online sometimes. It never became a real
       | issue but I knew I did it and it was embarrassing.
       | 
       | Once I started on tirzepatide, and then with retatrutide, the
       | "urge" to swap over to my PC between meetings and load up a game
       | is pretty much zeroed out.
       | 
       | Is this an "addiction" or a form of "abuse" similar to alcohol or
       | other drugs? I would have said no some time ago, but now I'm not
       | sure. I definitely feel like, looking back, I was more or less
       | "addicted" to video games. I don't want to romanticize it as some
       | sort of "escape", it just is what it was.
       | 
       | This was an unintended side effect (benefit?) of the drug for
       | sure, in addition to acute weight loss of course.
       | 
       | Unlike many others, even after titrating down and coming off the
       | GLP's, I have not felt the urge to binge food, video games, or
       | anything else. I maintain a healthy, active lifestyle and have
       | kept my weight exactly where I prefer it. My relationship with my
       | body and my time has massively improved. I feel like I am at risk
       | of sounding like a complete shill, obviously, but in my mind
       | these drugs can be something that absolutely has the potential to
       | turn life around for many, many people.
        
         | georgeburdell wrote:
         | I'm going to put on my Boomer pull-yourselves-up-by-the-
         | bootstraps hat, but are you concerned about the loss of grit
         | resulting from changing your behaviors without the drug?
        
           | afthonos wrote:
           | Definitely not GP, but I think it's pretty clear that
           | whatever grit there was to have, GP did not have it. "Die an
           | early death due to being overweight or build the grit" is
           | strictly worse than "lose the weight without building the
           | grit, or build the grit", and it's even more so when you
           | realize that "or build the grit" was never in the cards.
           | Because then the choice becomes "die an early death or
           | don't". Building the grit can be done on other, hopefully
           | less lethal, projects.
        
           | inopinatus wrote:
           | Turns out that this attitude was bullgrit all along.
        
           | hiddencost wrote:
           | _wet farting noise_
        
         | dalyons wrote:
         | side question - has retatrutide been different enough to
         | tirzepatide for you that you would recommend going to the extra
         | effort to source it?
        
         | Rudybega wrote:
         | I think it's probably still useful to distinguish addictions
         | with hardcore substance related barriers to quitting (think
         | withdrawals) from addictions where the barrier is a lack of
         | dopamine or serotonin or simple habituation.
         | 
         | For people with normal executive function, the second category
         | of problems should be fairly tractable to overcome, whereas the
         | first is still quite difficult.
         | 
         | The second only really becomes an issue when you have a bit of
         | executive dysfunction.
         | 
         | Maybe that distinction is important and one merits the term
         | addiction while the other doesn't? Though both categories seem
         | to be relatively treatable with drugs that massively improve
         | executive function, so the parallels are pretty glaring.
        
       | lordofgibbons wrote:
       | I've noticed that when I'm on Zepbound 2.5mg, I don't have the
       | strong urge to play video games and can focus on my projects.
       | Even if I do play video games while on it, I lose interest after
       | a maximum of half an hour.
        
       | jtrn wrote:
       | I hate these articles so much. The title should be: "Speculation
       | on how GLP-1a drugs could theoretically reduce alcoholism while
       | waiting for any real evidence".
       | 
       | 99% of promising mice studies does not result in clinical
       | practical application in humans. And theoretical associations and
       | mechanisms of action should not be promoted without huge asterisk
       | to contextualize how often such speculation are wrong.
       | 
       | If you complain about AI slop and don't see how this is just as
       | bad science slop, please go listen to Sabine Hossenfelder. This
       | is just as bad, and create just as much useless noise as AI
       | content does on the nett.
        
       | jnsaff2 wrote:
       | Just a single datapoint here. About 8 months after starting on
       | semaglutide I took a month off alcohol and by the time the month
       | was over had lost all interest for alcohol.
       | 
       | Almost 2 years now. I'm not religious about it and will
       | occasionally drink the celebratory glass of bubbles or a beer
       | (alcohol free if available) when it's hot outside.
       | 
       | Very interesting how it has worked.
        
         | themafia wrote:
         | I'm not trying to pick on you because I've seen this anecdote
         | on many occasions; however, it strikes me that people are quite
         | willing to walk past "personality changes" as a side effect of
         | a drug.
         | 
         | Does anyone else feel a slight sense of worry about this?
        
           | jnsaff2 wrote:
           | Worry about a positive side effect? No.
        
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