If I understand it correctly, GLP-1 drugs help people with weight loss. People are more healthy when they're not overweight, and GLP-1s help people get down to a healthier weight. So when we ask questions about do GLP-1s help this or that, isn't there a giant confounding variable here? That being overweight causes a litany of health issues has been common knowledge forever now. Thus, my (uninformed, intuitive) guess would just be that GLP-1s, which cause weight loss, also include the subsequent effects of healthy weight loss.
So why are we surprised then that people going from overweight to a healthy weight slows aging, or betters cardiovascular health as I've seen elsewhere? Aren't these already well-studied effects of healthy weight loss? Shouldn't these positive effects obviously just be attributed to weight loss, rather than the thing that causes the weight loss? And why are there articles about this stuff acting like this is unexpected?
I admit I'm a laymen and I hope don't sound too snide or critical here. I'm just kind of puzzled by this out of genuine curiosity.
2. Hunger signalling isn't the only thing GLP-1s do, so no, we should not just assume every effect stems from weight loss alone. E.g. the blood sugar regulation that makes them very effective for diabetes is not purely about weight management.
The best paper I've seen on this was the recently published and very aptly named:
"Pleiotropic effects of GLP-1 receptor agonists — a narrative review of extra-metabolic outcomes in adults" (2026)
https://journals.viamedica.pl/medical_research_journal/artic...
GLP-1 then addresses factor X, and the problems it causes, including weight gain.
Not that obesity doesn't independently cause problems but very plausible causality runs more than one way.
Then there are the mental effects, such as people reporting that they lost various addictive habits (gambling, compulsive shopping etc.)
https://www.health.harvard.edu/heart-health/weight-loss-drug...
I get that science has to be thorough, but how is it at all worth writing about that losing weight makes your risk of heart attacks lower? That GLP-1s are involved suddenly makes this news?
Again, not trying to be snide. I'm on the side of science here, but there's gotta be something the scientists are looking at that I'm not.
"GLP-1s cause an improvement in cardiovascular health"
if you said
"GLP-1s cause an improvement in cardiovascular health more than as would be expected by equivalent weight loss"
would that be more specific? Is this right?
>Building off this research, Deanfield is the lead author of a new study recently published in the journal The LancetTrusted Source that provides further evidence of semaglutide and lowered major cardiac event risk, regardless of how much weight a person loses while taking the GLP-1 medication.
>“Semaglutide has previously been shown in the SELECT trial to significantly reduce major adverse cardiovascular events in overweight/obese patients with known heart disease but without diabetes,” Chen explained. “This study analyzed the information from the SELECT study, and found that this benefit to cardiovascular health did not depend on how overweight patients were or how much weight they lost.”
>“This interesting finding suggests that the cardiovascular benefits of semaglutide act through a biochemical mechanism not dependent simply on changing the body weight of an individual,” he continued. “This may open up other avenues of research and therapies that could improve heart health.”
https://www.medicalnewstoday.com/articles/weight-loss-drug-h...
https://www.ehlers-danlos.com/effective-doses-of-low-dose-na...
Every gram of body weight needs energy to stay alive. If you are in a caloric deficit, you will lose weight until your energy expenditure matches the caloric intake. If you stay in "caloric deficit" forever you will actually starve by definition.
Properly defining what you mean (comparatively low caloric intake without defining it via the current weight) is actually quite tricky, as your height, body composition and physical activities are all inputs to what counts as a "normal" caloric intake.
Guess what we all here are doing. Using the magic keyboard.
Interesting, I wonder if someone will do a study where they pair a GLP-1 with tesamorelin to see if there's any synergy there in terms of fat reduction and reduced aging.
There seems some promise at times but I also struggle to see the recent slew of "GLP-1s cure X", where X is seemingly any ailment known to man, as much more than the next Big Pharma gold rush where the profits dwarf any eventual regulatory fines, and taxpayers and real patients are left with the costs.
- Marketing, to learn what / whom / how to sell: “They spend more on TV ads than R&D!”
- Basic R&D: “Look at all the conflicts of interest in this academic research!”
- Commercial R&D: “They’re just looking for ways to extend the patent lifetime of drugs that only exist because of government-funded basic R&D!”
- Back to the shareholders (mostly pensions and retirement accounts): “Billions of stock buybacks for Wall Street!”
What should the pharmaceutical companies with billions coming in from GLP-1’s be spending their money on?
(If anyone reading this feels inclined to say something like "But how would that benefit them?" -- well, if you restrict consideration to things they could do that benefit them, then it no longer seems so unreasonable if all their options look bad to the critically-minded. Maybe they should be doing things that benefit the rest of the world more and themselves less.)
Criticism does not have to mean preventing work, we can be critical especially of work that we find important.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.MR...
> Sponsorship of drug and device studies by the manufacturing company leads to more favorable efficacy results and conclusions than sponsorship by other sources. Our analyses suggest the existence of an industry bias that cannot be explained by standard 'Risk of bias' assessments.
And no! It's not unusual, nor does it mean the results are wrong. It just means there's a known bias towards results that favor the sponsor's interests that needs to be taken into account when evaluating the research. Again, that doesn't make it wrong. But it should make you cautious before thinking that a single study (in a very specific sub-population, at that) is necessarily going to generalize. It might. I hope it does! GLP-1's are awesome. But cautiously.
But ok, sure, drug companies bad. Man hn is really turning into Reddit these days.
"Competing interests G.A.M. serves as a research consultant for Merck, GlaxoSmithKline/ViiV, and Gilead. M.J.C. serves as a scientific advisor for TruDiagnostic. V.D. and R.S. are employees of TruDiagnostic. All other authors declare no competing interests."
These are known risk factors. I've never said drug companies are bad. I literally take corporate funding for my own research. But you also don't get to stick your head in the sand and ignore the competing interests that all make the research more likely to show favorable results. Again for those in the back: These results probably _are_ correct! But do they generalize? Will they hold up on replication with a larger population? Do they matter, or is the proxy they're measuring not actually relevant for long term things in humans? Dunno. That's the thing about a _statistical likelihood of bias_ -- you have no idea exactly how to apply it to a single paper other than to say "ok, known possibility of bias, interpret accordingly."
Again, what’s the evidence that this research in particular should be suspect? It looks a lot like all the other research that goes on in this space. Experimenting with biological systems & real humans is expensive, even when you’re mostly doing data collection. It needs funding!
I'll offer cystic fibrosis as an example. Trikafta may as well be a miracle drug. And CRISPR-based gene editing and replacements are being researched that could be an outright cure, as opposed to a 90% cure.
That puts most Western governments with limited budgets in a pickle, having promised their citizens modern medicine equitably at affordable cost, tax or otherwise.
Even though I personally expect them to be readouts of things that don't affect healthspan much, I don't have any more evidence than those trying to work out what they are. I've been wrong before, and also most tech development does not end up living to its promises, but without the investigation we'll never know.
> Big Pharma gold rush where the profits dwarf any eventual regulatory fines
With pharma malfeasance, the penalties are actually big enough, unlike most other fields. Unless you have something particular in mind?
I hear that word and I immediately think of "that" guy that runs the cocktails of additive interventions to "improve" it.
What would you propose instead? Who will do this research, with what funding, and why will they want to do it? And why would we trust that research more than this? Wouldn’t we scrutinize research carefully regardless of the source?
There are multiple alternative systems, as we see in other countries. But they all have tradeoffs and some really only make sense if some international entity is doing research somewhere else under a different set of rules.
And if you don’t have HIV?
Even in the highest-risk scenario (receptive anal sex) the risk is ~138/10,000 per exposure.
If your risk is 138/10000 per exposure and you have sex with your partner once a week for a year, that's about a 50% chance of infection overall. (Assuming the infection risks are independent, which they might not be.)
If it's 4/10000 per exposure then that's a 2% chance of infection after a year, which for sure isn't huge but I personally would take an annual 2% risk of getting HIV quite seriously.
(Obviously the "once a week" figure is an arbitrary choice for the sake of simplicity, and I am well aware that some people have a lot more sex than that and some have a lot less.)
but that's not really how the risk should be considered.
Medical marijuana was different, though. The negatives were known medically before and after. The push was almost entirely political and on social media. The few places medical marijuana were medically pushed were either for highly specific applications or as a harm reduction measure: Either as an alternative for patients who demanded opioids (medical marijuana isn’t actually a viable substitute for opioids in severe high level pain, but it’s common for patients to demand to be prescribed something “stronger” for lesser conditions and there was a real problem with opioid over prescription at the time) or from the sector of medicine that sees that patients are seeking out drugs anyway and thought this was a better way to control and monitor it. The way it worked out in practice became a laughable loophole where anyone who wants a card can pay $100 for a meeting with a prescriber who will give leading questions until you say the right things to get the card, which wasn’t even what the original medical marijuana proposals were about.
In the medical and research world, there was never an illusion that marijuana was actually entirely harmless and without drawbacks, except for fringe papers and a few politically motivated researchers.
:)
> data from a...clinical trial of 108 adults with HIV associated lipohypertrophy
:(
I have never seen a user name better fit a hacker news comment.
This also perfectly sums up the whole emotional roller coaster of modern science communication.Oh that could be cool (title)... Hey this might be good work... Fuck thats depressing I will never get this time back.
Long term? Who knows for sure. Semaglutide has been approved for 9 years. Liraglutide was 2009 and hasn't shown thyroid issues still. Exenatide has been available since 2005.
GLP-1s aren't new and haven't shown widespread negative issues beyond gastrointestinal upset, and that is typically fixed by... drinking more water. The trials in rats have pointed towards potential thyroid cancer risks but those haven't been seen in people.
I suppose we all could wind up with cancer in 10 years or something hypothetically, due to some unforeseen mechanism. But here's my story.
I went from 200lb to 140lbs at 5' 9" over 3 years. I feel great. I don't need to eat 1000 calories before bed just to sleep through the night. I focus better at work. Blood pressure is back to normal. HDL is back to normal. I can run without joint pain. I feel good about myself. I feel comfortable going on dates. I'm not a near-obese shut-in loner that can't be in a caloric deficit without wrecking my sleep.
Unless there are literally fatal side effects, these drugs seem pretty miraculous.
Extremely unlikely, GLP-1 receptor agonists have been on the market for more than 20 years now, exenatide being first used in 2005.
Controlled by increasingly unfeeling, sociopathic masters, who grow more and more in power. And now also do not age or get sick.
The power those at the top hold far exceeds any king or emperor throughout humanities history.
not like we can take GLP-1 even if it was affordable
btw soluble fiber helps people naturally secrete more GLP-1 but of course not on the same level as a dedicated drug
may I ask for how long now? are you athletic? have you experienced any muscle loss?
https://www.youtube.com/watch?v=dBnniua6-oM
Dr. Gil Carvalho (medical doctor, research scientist, science communicator) debunks parts of Lustig's 30-year-old claims:
https://www.youtube.com/watch?v=vdoDx9dIuNE
Nonetheless, Dr. Carvalho agrees with avoiding sugary drinks:
"We have a lot of recent evidence, recent studies after [Lustig's] talk. The link between soda and weight gain and obesity and other chronic diseases is quite strong."
Drink fewer sugary beverages, consume fewer calories (eat less), exercise, and drink less alcohol.
Seriously, in the first week you should feel a bit of nausea at .25mg. After 2-3 weeks you should see something, either weight loss (most) or gain (some).
Or you could be one of those who have no effect, which sucks. I'd go over your process with your provider, from storage to injection.
Why on earth would having no side effects suck? As long as its working (weight loss) then thats the ideal scenario.
https://www.medicalnewstoday.com/articles/weight-loss-drug-h...
even one caffeinated corn syrup slurpee that people consume like it's no big deal can be a quarter or more of your daily energy requirement. a few snacks on top of that and that leaves preciously little budget for real food.
How much are the pharma companies paying people to project this nonsense to trick people to take these drugs to make money out of it?
This is the new grift.
Caloric churn is putting the body's systems through their paces - at the very least for everything related to digestion. But really most of life is well described as pieces of a metabolic process.
If as a result of less caloric consumption you’re starving your cells of needed nutrients, maybe that’s the one that degrades earlier.
But burning that fuel is damaging.