6 ms·

The drug companies are very good at making new drugs with high profit potential look better than they are. I'm worried semaglutides are another fen-phen, Vioxx,

The drug companies are very good at making new drugs with high profit potential look better than they are. I'm worried semaglutides are another fen-phen, Vioxx, Quaaludes, Trovafloxacin or OxyContin. One thing to watch for is effect size: how big of an anti-aging effect does Ozempic confer relative to other good interventions? Were the subjects doing other solid anti-aging interventions like the Fasting Mimicking Diet (FMD)? If not, the 2 interventions might affect the same pathways with the result that if you are doing FMD, you get no additional benefit from Ozempic. Fen-phen is particularly interesting here because people reported that not only did it help them lose weight, it gave them more willpower and changed their personalities for the better.

some_random 1y ago
I think that's a completely reasonable concern to have, it doesn't seem to be the case wrt obesity but for the myriad of other potential effects it's important to keep in mind.
- hollerith 1y ago
  I'm not even ready to concede that it is a good weight-loss drug -- but then I haven't really investigated much, so I'm just repeating what I heard from researcher Ben Bikman and maybe other researchers. I heard that most people choose to discontinue it after 4 or 5 years or less, regain most or all of the weight, then refuse to go back on it.
  - throwforfeds 1y ago
    I've had a few friends on it. They definitely lost weight, but the GI issues were too much and when they went off of it they gained it all back.
    - alistairSH 1y ago
      I've read (anecdotes from people in the fitness/body-building space) that the default dosing could be too high for many people. And the side-effects seem to ramp up with the dose. IE, if you're getting weight loss at 1/2 the default dose, you might want to stay there, even if your MD wants you to increase to the default. [default uses loosely here - people build up from a low dose over the span of weeks/months] And the weight gain is due to a lack of lifestyle change. The drug just numbs your appetite, so you don't eat as much. If you go off the drug and return to over-eating, yep, you gain the weight back. I also suspect many people lose the weight too fast and go too far. "Ozempic butt" is a joke for a reason - people loose a bunch of fat, but the massive calorie deficit also means they aren't exercising (no energy, and they probably weren't before the drug either), so they've probably crashed their metabolism.
      - n8cpdx 1y ago
        I tried it. I started down about 80 lbs from my heaviest, but a good 40 lbs from ideal/20 lb from healthy weight. The first time I tried it I followed dosing guidelines for ramp up; side effects were horrible, didn’t lose much weight, and it just kept getting worse. Second time, after a few months off, I started at lowest dose and stayed there. Side effects were better to start but ramped up again. Eventually my digestion stopped entirely and I couldn’t eat without pain; that actually was good for weight loss but very unhealthy (e.g. despite being hungry and lightheaded the pain kept me from eating more than 400 calories). Eventually it passed but I couldn’t justify taking it after that. Basic side effects: exercise intolerance (higher starting rate, much faster increase exertion, chest pain after ~150bpm when previously I could run nearly an hour and go up past 180 without issue), fatigue in the morning (despite essentially maintaining my pre-ozempic nutrition), significant increase in resting heart rate, significant decrease in HRV, and digestive upset (basically alternating diarrhea and constipation). Many of these side effects are well known, others less so. Ozempic, when micro dosed, did help reduce hunger and make a weight loss diet easier to sustain, until the side effects got so bad I wanted to comfort eat. But mindfulness and healthy lifestyle are similarly effective without crippling side effects.
        alistairSH 1y ago
        Have you looked into Tirzepatide? Basically a combo of ozemspic plus a GIP drug. Again, anecdotes from bro-science, but appears to allow lower dosing and reduced side-effects.
        mapontosevenths 1y ago
        Try Zepbound. You lose more weight with far fewer side effects. Although, you may still have issues. It does just sound like there's something unique about your chemistry. I don't think that many of those side effects are even in the ballpark of normal.
        n8cpdx 1y ago
        I would like to try it, but I don’t think it is available from shady internet doctors and insurance won’t cover it because I’m not diabetic. Shady internet ozempic passes the cost-benefit test (barely, considering I can successfully lose weight without it it’s just hard). Full cost out of pocket it does not. Maybe in a few years. I would worry that the side effects I care about are not the side effects that others report being improved on zepbound.
    - mapontosevenths 1y ago
      > when they went off of it they gained it all back. To make matters worse, even ibuprofen is a scam. I stopped taking it and my headache came right back! More seriously, if you stick to it the GI issues go away after the first month for most people.
  - smiley1437 1y ago
    Tirzepatide (and likely other GLPs) have limitations that are rarely brought up in the general media - Patients have about 72 weeks to reach maximum loss, they don't lose any more weight after 72 weeks even on the highest dose. - Patients appear to immediately gain the weight back as soon as they stop taking it. It's right in the phase 3 trial outcomes paper: https://pmc.ncbi.nlm.nih.gov/articles/PMC10667099/ https://pmc.ncbi.nlm.nih.gov/articles/PMC10667099/ I suspect that this info is intentionally down-played so that it doesn't affect sales.
    - kion 1y ago
      I've been on Zepbound for ~25 weeks now and one of the first things my doctor told me was that this was a lifetime drug. He pointed out that I had a choice, of lifetime drugs. I needed to do something to get my cholesterol under control. That meant start statins now and likely add blood pressure meds and diabetes meds in the next 2-5 years. Alternatively I could start Zepbound, which would likely address all 3 and result in better quality of life in the next year. So far it seems like it is doing exactly that. I'm sure some people are going into this without that knowledge, but people are being told this is a lifetime commitment. What you don't see a lot of is why people stop taking it. There's some cases of people losing and then stopping, but the majority are because insurance is forcing people off of it. Just look at the recent CVS Caremark forced switch from Zepbound (2nd Gen) to Wegovy (1st Gen) in July.
      - pooloo 1y ago
        > Just look at the recent CVS Caremark forced switch from Zepbound (2nd Gen) to Wegovy (1st Gen) in July. This is something I wasn't aware of, are you on 2nd gen Zepbound then? My wife has been plateaued at an undesirable weight and has been wanting to try this, however, the VA refuses to support it regardless of the fact she fits their guidelines and requirements to receive it. They recently banned it due to costs. I prefer her to use Zepbound if we can get it, the question is how? We refuse to use the alternative methods where the drug is hand made to be equivalent to them as that seems very sketchy.
    - mapontosevenths 1y ago
glp1guide 1y ago
Don't worry, GLP1 RAs are nothing like those other drugs. In fact I'd really challenge you to examine even one of the correlations there, the scale of research, use, known side effects, effectiveness is completely different. The idea that people might only benefit from something like Ozempic a little if they were doing some other intervention before is irrelevant, because no one is doing those other interventions. Requiring people to suffer before providing useful, known-safe and well-researched medication is silly. Medication is technology.
reverendjames 1y ago
Quaaludes should definitely make a comeback.
- fuzzfactor 1y ago
  These were too strong a sleeping pill to be safe for driving, if you stayed awake or didn't wait for it to wear off all the way the next day. You could feel it was kind of a goofy intoxicant, but if you took one and laid down you slept like a log. I think there were some early incidents that would keep it from becoming a legitimate blockbuster, other sleep aids became more widespread and Quaaludes ended up more for retired people who didn't drive or didn't drive as much any more. Naturally the condos of South Florida were packed with those type residents like nowhere else. Mostly the old folks would take the first one and the next day feel like it was more potent than they thought. They were potent and most people wouldn't really need one the next night even if they took it for insomnia the night before. These patients weren't taking them every night, just the opposite, only occasionally, if ever again when they felt like they really needed it. One day, after a few years, some wild high-school kid with nothing else but pure rebelliousness and unruly behavior in mind, who will take any pill they find, finds out that grandma has a forgotten bottle in the medicine cabinet with 99 of them still in it. Tries it and likes it. Tells his friends. Within a few weeks hundreds of kids were finding vast repositories, selling them for $1 each and that's when they first started flying off the shelf. They probably cost about $6 a 100 for the prescription at the pharmacy, in 1970's dollars. Interestingly, they became a blockbuster only after it was no longer legitimate. This is also when pharma started to jack up their prices on a per-pill basis, before that the medical world was still like it really had never crossed their mind until then. For a number of years afterward new "patients" started preferring them too, on the black market a renewed prescription yielded over 10x the money the drug company made on the same bottle. Pharma was just cringing about it until they eventually got their skyrocketing underway. Still caught them again with opiates, especially Oxycontin.

some_random 1y ago

I think that's a completely reasonable concern to have, it doesn't seem to be the case wrt obesity but for the myriad of other potential effects it's important to keep in mind.

hollerith 1y ago
I'm not even ready to concede that it is a good weight-loss drug -- but then I haven't really investigated much, so I'm just repeating what I heard from researcher Ben Bikman and maybe other researchers. I heard that most people choose to discontinue it after 4 or 5 years or less, regain most or all of the weight, then refuse to go back on it.
- throwforfeds 1y ago
  I've had a few friends on it. They definitely lost weight, but the GI issues were too much and when they went off of it they gained it all back.
  - alistairSH 1y ago
    I've read (anecdotes from people in the fitness/body-building space) that the default dosing could be too high for many people. And the side-effects seem to ramp up with the dose. IE, if you're getting weight loss at 1/2 the default dose, you might want to stay there, even if your MD wants you to increase to the default. [default uses loosely here - people build up from a low dose over the span of weeks/months] And the weight gain is due to a lack of lifestyle change. The drug just numbs your appetite, so you don't eat as much. If you go off the drug and return to over-eating, yep, you gain the weight back. I also suspect many people lose the weight too fast and go too far. "Ozempic butt" is a joke for a reason - people loose a bunch of fat, but the massive calorie deficit also means they aren't exercising (no energy, and they probably weren't before the drug either), so they've probably crashed their metabolism.
    - n8cpdx 1y ago
      I tried it. I started down about 80 lbs from my heaviest, but a good 40 lbs from ideal/20 lb from healthy weight. The first time I tried it I followed dosing guidelines for ramp up; side effects were horrible, didn’t lose much weight, and it just kept getting worse. Second time, after a few months off, I started at lowest dose and stayed there. Side effects were better to start but ramped up again. Eventually my digestion stopped entirely and I couldn’t eat without pain; that actually was good for weight loss but very unhealthy (e.g. despite being hungry and lightheaded the pain kept me from eating more than 400 calories). Eventually it passed but I couldn’t justify taking it after that. Basic side effects: exercise intolerance (higher starting rate, much faster increase exertion, chest pain after ~150bpm when previously I could run nearly an hour and go up past 180 without issue), fatigue in the morning (despite essentially maintaining my pre-ozempic nutrition), significant increase in resting heart rate, significant decrease in HRV, and digestive upset (basically alternating diarrhea and constipation). Many of these side effects are well known, others less so. Ozempic, when micro dosed, did help reduce hunger and make a weight loss diet easier to sustain, until the side effects got so bad I wanted to comfort eat. But mindfulness and healthy lifestyle are similarly effective without crippling side effects.
      - alistairSH 1y ago
        Have you looked into Tirzepatide? Basically a combo of ozemspic plus a GIP drug. Again, anecdotes from bro-science, but appears to allow lower dosing and reduced side-effects.
      - mapontosevenths 1y ago
        Try Zepbound. You lose more weight with far fewer side effects. Although, you may still have issues. It does just sound like there's something unique about your chemistry. I don't think that many of those side effects are even in the ballpark of normal.
        n8cpdx 1y ago
        I would like to try it, but I don’t think it is available from shady internet doctors and insurance won’t cover it because I’m not diabetic. Shady internet ozempic passes the cost-benefit test (barely, considering I can successfully lose weight without it it’s just hard). Full cost out of pocket it does not. Maybe in a few years. I would worry that the side effects I care about are not the side effects that others report being improved on zepbound.
  - mapontosevenths 1y ago
    > when they went off of it they gained it all back. To make matters worse, even ibuprofen is a scam. I stopped taking it and my headache came right back! More seriously, if you stick to it the GI issues go away after the first month for most people.
- smiley1437 1y ago
  Tirzepatide (and likely other GLPs) have limitations that are rarely brought up in the general media - Patients have about 72 weeks to reach maximum loss, they don't lose any more weight after 72 weeks even on the highest dose. - Patients appear to immediately gain the weight back as soon as they stop taking it. It's right in the phase 3 trial outcomes paper: https://pmc.ncbi.nlm.nih.gov/articles/PMC10667099/ https://pmc.ncbi.nlm.nih.gov/articles/PMC10667099/ I suspect that this info is intentionally down-played so that it doesn't affect sales.
  - kion 1y ago
    I've been on Zepbound for ~25 weeks now and one of the first things my doctor told me was that this was a lifetime drug. He pointed out that I had a choice, of lifetime drugs. I needed to do something to get my cholesterol under control. That meant start statins now and likely add blood pressure meds and diabetes meds in the next 2-5 years. Alternatively I could start Zepbound, which would likely address all 3 and result in better quality of life in the next year. So far it seems like it is doing exactly that. I'm sure some people are going into this without that knowledge, but people are being told this is a lifetime commitment. What you don't see a lot of is why people stop taking it. There's some cases of people losing and then stopping, but the majority are because insurance is forcing people off of it. Just look at the recent CVS Caremark forced switch from Zepbound (2nd Gen) to Wegovy (1st Gen) in July.
    - pooloo 1y ago
      > Just look at the recent CVS Caremark forced switch from Zepbound (2nd Gen) to Wegovy (1st Gen) in July. This is something I wasn't aware of, are you on 2nd gen Zepbound then? My wife has been plateaued at an undesirable weight and has been wanting to try this, however, the VA refuses to support it regardless of the fact she fits their guidelines and requirements to receive it. They recently banned it due to costs. I prefer her to use Zepbound if we can get it, the question is how? We refuse to use the alternative methods where the drug is hand made to be equivalent to them as that seems very sketchy.
  - mapontosevenths 1y ago

glp1guide 1y ago

Don't worry, GLP1 RAs are nothing like those other drugs. In fact I'd really challenge you to examine even one of the correlations there, the scale of research, use, known side effects, effectiveness is completely different. The idea that people might only benefit from something like Ozempic a little if they were doing some other intervention before is irrelevant, because no one is doing those other interventions. Requiring people to suffer before providing useful, known-safe and well-researched medication is silly. Medication is technology.

reverendjames 1y ago

Quaaludes should definitely make a comeback.

fuzzfactor 1y ago
These were too strong a sleeping pill to be safe for driving, if you stayed awake or didn't wait for it to wear off all the way the next day. You could feel it was kind of a goofy intoxicant, but if you took one and laid down you slept like a log. I think there were some early incidents that would keep it from becoming a legitimate blockbuster, other sleep aids became more widespread and Quaaludes ended up more for retired people who didn't drive or didn't drive as much any more. Naturally the condos of South Florida were packed with those type residents like nowhere else. Mostly the old folks would take the first one and the next day feel like it was more potent than they thought. They were potent and most people wouldn't really need one the next night even if they took it for insomnia the night before. These patients weren't taking them every night, just the opposite, only occasionally, if ever again when they felt like they really needed it. One day, after a few years, some wild high-school kid with nothing else but pure rebelliousness and unruly behavior in mind, who will take any pill they find, finds out that grandma has a forgotten bottle in the medicine cabinet with 99 of them still in it. Tries it and likes it. Tells his friends. Within a few weeks hundreds of kids were finding vast repositories, selling them for $1 each and that's when they first started flying off the shelf. They probably cost about $6 a 100 for the prescription at the pharmacy, in 1970's dollars. Interestingly, they became a blockbuster only after it was no longer legitimate. This is also when pharma started to jack up their prices on a per-pill basis, before that the medical world was still like it really had never crossed their mind until then. For a number of years afterward new "patients" started preferring them too, on the black market a renewed prescription yielded over 10x the money the drug company made on the same bottle. Pharma was just cringing about it until they eventually got their skyrocketing underway. Still caught them again with opiates, especially Oxycontin.