Hacker News Reader

Comment by cj | Hacker News Reader

After using them, I think GLP-1’s will eventually be rebranded as a weight management / weight maintenance drug rather than a weight loss drug in order to appeal to the masses.

It’s a very interesting feeling to feel like you’re in full control of what you eat, not influenced by random cravings or hunger.

In my case I’m planning to only stay on it another month or 2 to drop 10lbs. I can easily see people cycling on/off this drug throughout the year to keep weight in check while removing will power from the equation completely. It’s quite remarkable.

View on HN

They might be branded that way, but that's not what they are. They have dramatic effects on the metabolic pathway and insulin response that need to be carefully considered if you're not actually diabetic.

I recommend that you listen to the most recent Peter Attia podcast, which is a 2+ hour interview with Ralph DeFronzo (diabetes expert) where he goes deep into the effects of GLP-1 agonists on insulin response and other metabolic pathways. I came away with the impression that we're being too casual with how these drugs are being used -- if you're overweight these impacts are probably all for the good, but if you're not, it's more questionable.

https://peterattiamd.com/ralphdefronzo/

I’ll have to rewatch that video. Saw it a couple days ago and walked away with the opposite take. DeFronzo spent a whole lot of time heavily praising the generation of drugs (including the next generation in phase 2 trials)

If there’s a specific part you remember talking about the negatives I’d be interested to hear.

I legitimately have a difficult time finding anything negative when researching the drug, other than tolerable side effects like GI upset.

He's praising them for people with clear metabolic syndrome, and I'm reading between the lines as someone with prior knowledge. As a simple example, while it's probably good to inhibit gluconeogenesis in people with elevated A1c, doing so in a healthy person could lead to hypoglycemia.

I don't have a list of exact timestamps, but there are multiple places where he discusses the impacts of the GLP-1 agonists (of various generations) on insulin signaling, glucose transport etc., and the conversation is generally complex, nuanced, and wide-ranging. We don't understand everything these drugs are doing, but they're clearly banging around a complicated metabolic/hormonal system with a big, blunt hammer.

Specific part of the interview that talks about GLP-1 safety with DeFronzo and Attia: https://www.youtube.com/watch?v=QGIFdakceHM

Yeeeeah, he says that "they're quite safe", but it's in the context of a wider conversation focused on people with metabolic syndrome. I wouldn't be eager to extrapolate from that comment to "let's put this in the water supply" (exaggerating for the sake of argument).

A rebranding to a non-prescription drug will depend on how the prevalence × severity of side effects [0] turns out longer-term. I hope that you are right, but it seems too early to tell.

[0] https://www.sciencedirect.com/science/article/pii/S266736812...

https://www.gov.uk/drug-safety-update/glp-1-receptor-agonist...

"Gastrointestinal side effects" I assume that is code for excessive and frequent evacuation of watery feces.

People seem to handle it very differently, according to my doc. I never had issues while taking Mounjaro or Synjardy (a prescription pill for diabetes management with similar side effects) alone, but the two together meant I could count on a couple of bad days a week.

Sidebar: Mounjaro changed my life. I'd been very diabetic (300 units of insulin a day) for years on end. Taking that much insulin, my normally large frame got very large indeed. A couple of months into the Mounjaro and I was off insulin; a year into it and I was down 75 lbs and healthier than I'd been in 20 years.

It’s actually the opposite. GLP-1s slow down the digestive tract, so my shits are far more well formed than before. This isn’t like olestra, where excess fat caused diarrhea.

Ok I'd been considering it already, but now I'm sold. I have the transit time of a canid.

fwiw tirzepatide (likely the GIP component) cleared up my lifelong IBS within days of my first dose.

I consider it a likely lifelong medication now simply due to that night and day difference to my life. It’s extremely rare I have a day where I need to be within 5 minutes of a restroom now.

My primary care doctor mentioned this might be a side effect when I first started, and she ended up being more correct than even she expected to be.

It’s wild. I’ve never experienced burping food and tasting what I ate earlier, food just kinda rolls right through. Now, I get to really enjoy it a second time.

Who needs an appetite suppressant when they have comments like these?

Let me know when you need a little appetite adjustment. Free of charge!

“common gastrointestinal side-effects of GLP-1RAs treatment (including nausea, vomiting, diarrhoea and constipation) can persist for several days and may affect more than 1 in 10 patients”

For me, nausea only appears when I eat poorly - poor quality, or more than I should. Also increasing a dose can cause a bit of nausea for a few hours.

In this sense, I see adoption among some people as akin to nootropics or attention management drugs like modafinil. A way to have more control over your own mind. Interesting times, I guess, but caveat emptor.

Reply on news.ycombinator.com