5 ms·

I'm surprised that this article doesn't appear to mention the RCT on semaglutide and alcohol use disorder by Hendershot et al. that was published in JAMA Psychi

by dynm 7mo ago

I'm surprised that this article doesn't appear to mention the RCT on semaglutide and alcohol use disorder by Hendershot et al. that was published in JAMA Psychiatry in early 2025 (though it's possible I missed it) https://doi.org/10.1001/jamapsychiatry.2024.4789 https://doi.org/10.1001/jamapsychiatry.2024.4789 This was largely portrayed as a great result in the popular press although personally I think it was a bit of a disappointment given all the amazing anecdotes https://dynomight.net/glp-1/ https://dynomight.net/glp-1/

llm_nerd 7mo ago
What made it a disappointment? Over only 9 weeks, which is a very short time for habit changes to take hold, there were measurable, statistically significant effects. And at the highest dose was just 1mg / week for one single week at the end, where the maintenance mode for many is 2.4mg / week. Seeing such an effect in just 9 weeks, 90% of that time being at low ramp up doses, is astonishing.
- dynm 7mo ago
  The results for how much people actually drank in daily life were basically zero. No effect at all. The effects you're talking about are for a weird lab experiment where they sort of had people sit there in the lab and drink (or not). A huge percentage of people declined to participate in that experiment, too, which makes causality non-obvious.
  - llm_nerd 7mo ago
    The effects you're talking about are for a weird lab experiment where they sort of had people sit there in the lab and drink (or not). Where people on GLP-1s -- in a randomized, double-blind study, notably -- chose to partake of less. I cannot fathom how you dismiss this. It's a 9 week study at very low doses, and already a significant measurable effect was seen. Now if this wasn't a double-blind study I would dismiss it, but otherwise yeah, it matters. People who have drinking habits will take a long time to adopt new habits. I would never expect to see baseline behaviour changes in so short a time. But their non-habit desire for alcohol clearly was diminished, hence the lab outcomes.
    - dynm 7mo ago
      When you have lots of non-randomized dropouts from a randomized trial, that greatly weakens the causal link. The results are effectively non-randomized. Meanwhile the evidence from actual drinking levels was much stronger (far fewer dropouts) and showed zero effect. Before this trial was done, you may have predicted that there would be positive results for the lab experiment but zero results in ecological conditions. But I think that prediction would be quite unusual. For anyone who expected results in ecological conditions (like me), this was disappointing.
      - llm_nerd 7mo ago
        It was a tiny study, and one arm had someone dropout because they had COVID. The difference was minuscule. You are being bizarrely selective in discarding the part you don't like, while holding the rest as demonstrative. "But I think that prediction would be quite unusual." Would it? Who in the world would guess that small ramp-up doses of a semaglutide (0.25, 0.5, and 1mg, the first two doses over 89% of the study duration. The average maintenance dose is 2.4mg) would immediately undo long-earned core habits over just two months? It's a rather absurd study.

by dynm 7mo ago

llm_nerd 7mo ago

What made it a disappointment? Over only 9 weeks, which is a very short time for habit changes to take hold, there were measurable, statistically significant effects. And at the highest dose was just 1mg / week for one single week at the end, where the maintenance mode for many is 2.4mg / week. Seeing such an effect in just 9 weeks, 90% of that time being at low ramp up doses, is astonishing.

dynm 7mo ago
The results for how much people actually drank in daily life were basically zero. No effect at all. The effects you're talking about are for a weird lab experiment where they sort of had people sit there in the lab and drink (or not). A huge percentage of people declined to participate in that experiment, too, which makes causality non-obvious.
- llm_nerd 7mo ago
  The effects you're talking about are for a weird lab experiment where they sort of had people sit there in the lab and drink (or not). Where people on GLP-1s -- in a randomized, double-blind study, notably -- chose to partake of less. I cannot fathom how you dismiss this. It's a 9 week study at very low doses, and already a significant measurable effect was seen. Now if this wasn't a double-blind study I would dismiss it, but otherwise yeah, it matters. People who have drinking habits will take a long time to adopt new habits. I would never expect to see baseline behaviour changes in so short a time. But their non-habit desire for alcohol clearly was diminished, hence the lab outcomes.
  - dynm 7mo ago
    When you have lots of non-randomized dropouts from a randomized trial, that greatly weakens the causal link. The results are effectively non-randomized. Meanwhile the evidence from actual drinking levels was much stronger (far fewer dropouts) and showed zero effect. Before this trial was done, you may have predicted that there would be positive results for the lab experiment but zero results in ecological conditions. But I think that prediction would be quite unusual. For anyone who expected results in ecological conditions (like me), this was disappointing.
    - llm_nerd 7mo ago
      It was a tiny study, and one arm had someone dropout because they had COVID. The difference was minuscule. You are being bizarrely selective in discarding the part you don't like, while holding the rest as demonstrative. "But I think that prediction would be quite unusual." Would it? Who in the world would guess that small ramp-up doses of a semaglutide (0.25, 0.5, and 1mg, the first two doses over 89% of the study duration. The average maintenance dose is 2.4mg) would immediately undo long-earned core habits over just two months? It's a rather absurd study.