In an analysis of more than 6,800 colon cancer patients across all University of California Health sites, researchers found that those taking glucagon-like peptide-1 (GLP-1) medications were less than…
A new University of California San Diego study offers compelling evidence that GLP-1 receptor agonists — the class of drugs behind Ozempic, Wegovy and Mounjaro, for example — may do more than regulate blood sugar and weight. In an analysis of more than 6,800 colon cancer patients across all University of California Health sites, researchers found that those taking glucagon-like peptide-1 (GLP-1) medications were less than half as likely to die within five years compared to those who weren’t on the drugs (15.5% vs. 37.1%).
The study, led by Raphael Cuomo, Ph.D., associate professor in the Department of Anesthesiology at UC San Diego School of Medicine and member of UC San Diego Moores Cancer Center, used real-world clinical data from the University of California Health Data Warehouse to assess outcomes across the state’s academic medical centers. After adjusting for age, body mass index (BMI), disease severity and other health factors, GLP-1 users still showed significantly lower odds of death, suggesting a strong and independent protective effect.
The survival benefit appeared most pronounced in patients with very high BMI (over 35), hinting that GLP-1 drugs may help counteract the inflammatory and metabolic conditions that worsen colon cancer prognosis. Researchers believe several biological mechanisms could explain the link. Beyond regulating blood sugar, GLP-1 receptor agonists reduce systemic inflammation, improve insulin sensitivity and promote weight loss — all factors that can dampen tumor-promoting pathways. Laboratory studies also suggest that GLP-1 drugs may directly prevent cancer cell growth, trigger cancer cell death and reshape the tumor microenvironment. However, the study authors emphasize that more research is needed to confirm these mechanisms and determine whether the survival benefit observed in this real-world analysis represents a direct anti-cancer effect or an indirect result of improved metabolic health.
Cuomo notes that while these results are observational, they underscore an urgent need for clinical trials to test whether GLP-1 drugs can improve cancer survival rates, especially for patients with obesity-related cancers.
The study appeared in Cancer Investigation on Nov. 11, 2025.
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> However, the study authors emphasize that more research is needed to confirm these mechanisms and determine whether the survival benefit observed in this real-world analysis represents a direct anti-cancer effect or an indirect result of improved metabolic health
Given it’s an observational study, I would bet on the latter. It’s really hard to know you’ve controlled for all confounding factors, and there’s a strong null hypothesis because we know that losing weight can have huge and wide-ranging health benefits.
By cyrusradfar 2025-11-1221:566 reply Agreed.
I'm a big fan of intermittent and water fasting. Have seen things in my blood work that doctors would require me on meds to reverse. Outside of that, I can't speak to the positive impacts on my mood, and general ability to focus.
The simplest solution to a lot of problems is consuming less with the assumption that, most of us (maybe not you), have a lot of spare energy sitting around.
A lie that we don't unlearn as we grow up is we "require" three meals a day. This is true for children who need obscene amounts of energy to grow, but, not for us desk-bound adults.
In the end, giving the body a break to heal by fasting or just consuming significantly less is going to leave more resources for the body energy to deal with other things.
An interesting FYI is a comment made by Peter Attia on his podcast.
He had a patient with metabolic markers that were not improving and they had exhausted all the typical avenues. Presumably they were things like weight loss.
They put the patient on GLP-1 but injected into the thighs (or butt, I don't recall) for the metabolic benefits without the hunger blunting effects.
It seems like GLP1, even in skinny patients (implied by Attia in this particular case), has metabolic benefits.
The longevity community seems to be hinting that there may be geroprotective aspects of GLp1 as well, so we may be looking at the benefits beyond weight loss for metabolism.
By ifwinterco 2025-11-1310:585 reply It shouldn't make any difference where you pin it, it's systemic it just has to be administered subcutaneously because it's a peptide and it isn't orally active.
Don't listen to these YouTubers about health and fitness, most of them are clueless
By op00to 2025-11-1314:53 It shouldn't, and yet for me it seems to make a difference! I don't think it's placebo, because I am really losing weight. My anecdata: When I start with a particular dose of GLP-1, I inject in thigh. I get strong appetite suppression, heart rate increase, digestion slow down etc. After some time, the effect decreases as my body adjusts. I then move injection to abdomen, and I get a huge bump in suppression, systemic effects, etc. No idea why this happens, but I've seen it with Zepbound and 5, 7.5, and 10mg. It's allowed me to stay on each dose for far longer than my doctor expected.
By itchyouch 2025-11-1322:14 There were no recommendations.
Usually this type of anecdata becomes the basis of legitimate, controlled studies and over time can inform and/or adjust.
It would be premature to simply write off all influencers or limiting to only accept the medical profession as the immutable truth.
The reality tends to exist somewhere in the middle, outside of a formal proof.
I've listened to many health influencers and among the legitimate and balanced tend to be Rhonda Patrick and Peter Attia.
Attia provides guidelines for how to think about items, but usually it's the fan base that tends to sully the messaging as the base tends to be far more polarized and dogmatic over bits.
It is interesting to see that there is another poster confirming a slightly different effect though. Regardless of things being "systemic", just understanding that fluids dynamics are complex, I imagine diffusion of a systemic molecule like GLp1 could possibly be variable? Or perhaps there is a localized tissue fatigue?
Many potential options do exist to propose as hypothesis.
By floor2 2025-11-1417:32 Peter Attia is a graduate of Stanford medical school and spent 5 years in surgical residency at Johns Hopkins, and his podcast is largely using his expertise to give context to recently published research. His opinions are always pretty directly linked to peer reviewed research and he updates his stances as new research becomes available and explains why (eg, his shift away from fasting).
He really shouldn't be lumped in with the general "health and fitness Youtubers".
By itchyouch 2025-11-1322:28 While the area under the curve for glp1 administration may be the same, good chance that the story is informing us of a mechanism such as the absorption rate between two different sites.
Slower absorption in the thigh may blunt the immediate peak dosing and the acute hunger effects.
As always, the small details matter. I'd guess that pharmacology also has their own thundering herd problem with the dosing of certain drugs.
One of the interesting bits about pharmacology seems to not be the active molecule as much as the innovations in delivery mechanism.
By avgDev 2025-11-1314:49 Pseudoscience scares me. There are so many people that believe this nonsense and basic understanding of medicine disproves many of those claims.
By asmor 2025-11-138:59 (Outer) Thigh, upper arms and stomach are the on-label injection sites for these drugs.
By gavinray 2025-11-1318:21
Thanks for the dumbest thing I've read all day> They put the patient on GLP-1 but injected into the thighs (or butt, I don't recall) for the metabolic benefits without the hunger blunting effects.
Awesome insight. It's not the disability I have, it's that I have never tried healing by fasting. Of course. Because my body was always busy trying to eat food instead of fixing and regrowing all the malformed tissue. Because that's how it works. When a person without legs starts to fast, the legs will suddenly develop.
It would be sensible for you to examine and interrogate why reading a general and fairly anodyne opinion about what might be a solution to a problem some people have led you to interpret it as a prescriptive and judgemental suggestion about the specific problem you specifically have.
By trallnag 2025-11-1313:15 In my mind it is a slippery slope that leads to a sickly Steve Jobs eating kilograms of raw carrots.
Obviously a healthy lifestyle is good. And this includes not eating over your requirements. But sometimes there is actually something wrong. And in these cases, first trying out to just eat healthy can worsen the situation by delaying proper treatment. And proper treatment does equal a bunch of pharmaceutical drugs.
By mock-possum 2025-11-1316:20 I disagree, I think it’s fairly easy to read this passage in particular
> The simplest solution to a lot of problems is consuming less with the assumption that, most of us (maybe not you), have a lot of spare energy sitting around.
as energy-woo / thanks-I’m-cured material.
You can weasel your way around criticism by calling it “a general and fairly anodyne opinion about what might be a solution to a problem some people have,” but consider -
It does make sense that someone who’s struggled with a chronic condition would be tired and embittered by the endless snake oil evangelizing they’ve had to endure, on top of already struggling with their health.
(Not that fasting doesn’t work for some people, as you say! it’s more the grandiose claim that it’s “The simplest solution to a lot of problems” coupled with some vague anecdote about blood work and knowing better than doctors that waves a red flag)
By cyrusradfar 2025-11-139:15 Appreciate the thoughtful retort. Have a good one.
By codr7 2025-11-1313:42 Yeah, it's been a gradual process for me, feeling comfortable with being hungry.
But the less I eat, the better my health gets; I'm down to one normal sized meal per day, have been doing that for months.
I for one don't "require" three meals a day, but I'm hungry in the morning, ergo, I like breakfast.
It's not so much about how often you eat but what and how much. Generally speaking, of course, I can't speak for any benefits of intermittent fasting (assuming equal daily calorie / macronutrient intake) because I'm uneducated in that regard. But TL;DR, I will agree that desk jockeys will need less calories than people with a more active job or lifestyle, and people need to adjust their lifestyle accordingly else they'll gain weight.
Maybe this goes away after a while, but when I tried this in the past I get so hungry I can't think or work. So clearly it's a non-starter for me on work days.
By codr7 2025-11-1313:45 It takes time to get used to the feeling, to accept that it's not dangerous, quite the opposite.
Also the body gets used to not being full all the time, it will stop signalling so hard.
Try it in the weekends first? Once you start enjoying the feeling, and you will, it will happen by itself.
By dredmorbius 2025-11-143:36 One approach is to first reduce carbs (and particularly highly-processed carbs), then begin intermittent fasting. An initial lower-carb diet for 2--4 weeks may help with compliance on the IF diet.
By codr7 2025-11-1313:48 Yeah, the problem with mornings is that it's probably the worst time of day to eat.
Because the body flushes all stored up energy when you wake up, likely an evolutionary adaptation as breakfast was rarely served on a silver plate.
ALmost everyone who shares their positive, any length fasting experience here gets downvoted. I will always upvote them. Ive done two 48 hour fasts and they were so relaxing and felt so natural. It just feels great to occasionally go about your day and not eat anything. Your gut tries to heal itself in between meals. The fact that almost all of HN just cant stand anyone mention they fast with positive benefits (and mounting evidence) is kidna sad. I guess every community has to be exceptionally closed minded about something.
By dredmorbius 2025-11-143:38 <https://news.ycombinator.com/item?id=9562917>
Just make your point, as clearly and persuasively as possible.
By lazyasciiart 2025-11-1312:17 If you include as much meta-commentary every time, you’re certainly going to get downvoted.
By l5870uoo9y 2025-11-138:162 reply There is no such thing as water fasting. I would characterize it as an eating disorder.
Of course. That's why the nobel prize in medicine in 2016 was awarded to a cell biolgoist studying cellular autophagy for over a decade. It must be why glucose is not an essential dietary macronutrient and our liver can synthesizie it endogenously from fats and proteins (it just felt like doing that one day and stored all those chemical pathways in our genes I guess). That must also be why ketones produced from our fat stores burn so cleanly with less reactive inflammatory byproducts. In fact the cells in our brain actually prefer ketones to glucose. There's no such as water fasting. It's just random chance that when the body is in a state of ketosis it suppresses ghrelen and other hunger hormones or that countless other chemical pathways (de)activate or change. That's right the body has absolutely no design or adaptation for scarcity of food. Water fasting is totally foreign to the human body, that's why whenever we study ancient cultures...we find they practiced purposeful fasting. There's just no such thing as water fasting, it must be a modern eating disorder.
There's no chance it has anything to do with the last few million years of our evolution. It has no benefit or relevance now.
By l5870uoo9y 2025-11-1311:321 reply Took "water fasting" to mean fasting even without water, apparently it is the opposite.
By InMice 2025-11-1311:52 LOL total misunderstanding then. No problem.
By cyrusradfar 2025-11-139:19 Umm.
Sources?
- https://en.wikipedia.org/wiki/Fasting - https://zerolongevity.com/blog/the-history-of-fasting/
Interesting that GLP-1s might have different effects on cancer _incidence_ vs. cancer _survival_.
A different study "GLP-1 Receptor Agonists and the Risk of Thyroid Cancer" was published in the Diabates Care journal in February 2023*
The conclusion of the 2023 study: "we found increased risk of all thyroid cancer and medullary thyroid cancer with use of GLP-1 RA, in particular after 1–3 years of treatment."
I wonder what the mechanistic hypothesis could be for GLP-1s increasing thyroid cancer _incidence_ (the probability of thyroid cancer occurring in patients taking GLP-1s) but increasing colon cancer _survival_ (the probability of surviving in patients taking GLP-1s who have colon cancer).
Of course there are numerous important differences across the studies (cancer type, France vs. USA data, etc.), I'm just curious about a why this might be the case.
*https://diabetesjournals.org/care/article-abstract/46/2/384/...
By mr_luc 2025-11-1315:32 I'd be cautious for the same reason: thyroid cancers are also positively associated with obesity, and people who take GLP-1s are often obese.
Below a table, it says "adjusted for social deprivation index, hypo- and hyperthyroidism, and use of other antidiabetic drugs..." -- but nothing about obesity.
What if the GLP-1-prescribed patients tended to be more obese?
Yeah, most GLP-1 benefits (or even adverse effects, like muscle loss) seem to be caused by the weight loss. We already knew obesity massively increases risk from a host of diseases, but GLP-1s are still treated with scepticism of the "oh but what about the side-effects we don't know about?!" variety?
Source?
There’s growing evidence of cardioprotective effects independent of weight loss.
Eg https://www.thelancet.com/journals/lancet/article/PIIS0140-6...
> The cardioprotective effects of semaglutide were independent of baseline adiposity and weight loss and had only a small association with waist circumference, suggesting some mechanisms for benefit beyond adiposity reduction.
By rickydroll 2025-11-1222:22 They also help with slowing the progression of CKD
https://www.kidneyfund.org/treatments/medicines-kidney-disea...
Someone has to start a study where they give GLP-1 to skinny people and see what happens. Why it hasn't been done yet?
By anovikov 2025-11-1310:39 They won't, GLP-1 has almost no direct effect on skinny people. Many women with BMI around 22-23 are trying them to lose weight to match beauty standards and usually end up disappointed, not able to drop more than 1-2 kilos.
By freetime2 2025-11-1320:30 The article also says that the effects persist after adjusting for BMI:
> After adjusting for age, body mass index (BMI), disease severity and other health factors, GLP-1 users still showed significantly lower odds of death, suggesting a strong and independent protective effect.
The observed reduction in mortality is also quite large:
> Health sites, researchers found that those taking glucagon-like peptide-1 (GLP-1) medications were less than half as likely to die within five years compared to those who weren’t on the drugs (15.5% vs. 37.1%).
More research is needed, but if I were diagnosed with colon cancer I would definitely be asking my doctor about the risks vs. potential benefits of getting on GLP-1 meds based on this study alone.
By surfsvammel 2025-11-1221:147 reply I am on GLP-1 (very low dose), and I’ve found that it seems to help me moderate my alcohol consumption as well. Maybe some thing like that could also be contributing to the effect.
By donsupreme 2025-11-1222:161 reply I hypothesize that the appetite-suppressing effect of GLP-1 agonists contributes to the normalization of dopamine signaling in the brain. By mitigating the exaggerated dopamine fluctuations seen in food and sugar addiction, GLP-1 may promote a return to dopamine homeostasis, thereby reducing compulsive or addiction-like reward-seeking behaviors.
Same here. There's less wanting it but also, if I do indulge even one small glass of wine, the side effects are awful: broken sleep, acid reflux and a hangover the next day. It really slaps you in the face for indulging
By Cthulhu_ 2025-11-1310:03 Harsher side-effects to drinking sounds like an effective deterrent (although you'd think people would quit after that one hangover they'll never forget). Works for me with candy, a lot of it gives me tooth pain. My teeth are otherwise healthy, no cavities or anything.
By fgimenez 2025-11-1222:48 They have a lot of anecdotal, observational, and emerging RCT evidence on their effects on substance consumption and abuse.
The biggest effect and best tested is on alcohol use disorder. Mechanistically we don't know if it's through some complex reward mechanism, or something simpler like "alcohol is a calorie and you consume fewer calories." The JAMA study showed that GLP-1 reduce Heavy Drinking Days (>2 drinks/day), but did not reduce overall drinking days. This would imply the simple mechanism -> it's hard to drink a lot of calories even if you do enjoy a drink.
More anecdotal evidence showing this effect in opiates, but nothing in an RCT yet.
So far, nothing has worked in stimulants. Cocaine and Meth abuse are insanely difficult to manage therapeutically right now.
Is there evidence for addiction tendencies in general? Or is it something specific to alcohol?
By toomuchtodo 2025-11-1222:02 A Brain Reward Circuit Inhibited By Next-Generation Weight Loss Drugs - https://www.biorxiv.org/content/10.1101/2024.12.12.628169v1.... | https://doi.org/10.1101/2024.12.12.628169 - December 17rd, 2024
Glucagon-like peptide 1 agonist and effects on reward behaviour: A systematic review - https://www.sciencedirect.com/science/article/pii/S003193842... | https://doi.org/10.1016/j.physbeh.2024.114622 - Physiology & Behavior Volume 283, 1 September 2024, 114622
GLP-1 for Addiction: the Medical Evidence for Opioid, Nicotine, and Alcohol Use Disorder - https://recursiveadaptation.com/p/the-growing-scientific-cas... - May 14th, 2024
The central GLP-1: implications for food and drug reward - https://www.frontiersin.org/journals/neuroscience/articles/1... | https://doi.org/10.3389/fnins.2013.00181 - Front. Neurosci., October 13th, 2013
By zemvpferreira 2025-11-1221:28 I’m about to go to the cinema so I can’t find you references, but there’s a lot of anecdotal evidence at least of glp1’s curbing all sorts of addictive behaviour. I personally started Mounjaro last week and my coffee cravings have gone way, way down for the first time in my adult life.
By surfsvammel 2025-11-1221:25 I don’t know! Think I’ve seen a headline somewhere, but can’t remember where. Quick search should help you :)
To me, it’s anecdotal, of course, but I have same sense of being in control over alcohol intake as food intake.
Basically makes it much easier for me to avoid binging.
By SoftTalker 2025-11-1221:51 I believe there is, I don't recall the source but have read that these drugs work by reducing cravings. So they have shown at least hints that they can work on any addictive behavior, not just overeating.
By CobrastanJorji 2025-11-139:14 From my friends on GLP-1s, I'm pretty sure that it's mostly that it makes you really sick fairly quickly when you drink even in moderation.
By pretzellogician 2025-11-1314:15 It depends on the person, but for some (including me) a low dose is enough.
Conversely, for some (including me) a moderate dose has intolerable side effects.
By JumpCrisscross 2025-11-142:45 Would you mind sharing what BMI you had when you started treatment and through whom you went? Curious about the low/micro dose effects.
By _1 2025-11-1313:32 Same. two drinks and I'm done
Maybe I'm just an aging cynic, but I'm waiting for the other shoe to drop when it comes to GLP-1s. There have been so many claims of positive benefits that it almost seems too good to be true. With them being so expensive, the producers have every incentive to upsell using any study they can get their hands or money on.
If it's all upside, then I'm happy to be wrong.
By robbomacrae 2025-11-1220:264 reply There have been some. I've heard about eyesight related issues. A quick google found this article [0] where results showed that people using GLP-1 drugs were 68.6 times more likely to develop certain types of vision problems.
[0]: https://www.aao.org/newsroom/news-releases/detail/do-glp-1-d...
This is also an extremely rare vision problem. So absolute numbers are very tiny. The absolute numbers for diabetes, weight related problems, etc far dwarf this.
By robbomacrae 2025-11-1221:021 reply Right. On the whole I think these things are incredible.. looking to try myself after reading here in HN the other day about it working for all sorts of distractions. Just wanted to point out it's not all sunshine and rainbows which would certainly be suspicious.
By azinman2 2025-11-1320:31 Literally too much water or aspirin can kill you. Some people are allergic to avocados. Driving kills huge numbers of people daily. Everything is about risk/reward, and looking at the macro picture. And right now the comorbidities for obesity are terrible in huge absolute numbers… something that GLP-1’s can take down in significant magnitude. Unless we learn that the majority of users end up with something worse than obesity, they’re a huge win for public health.
By asmor 2025-11-139:05 A large drop in HbA1c does cause early worsening of diabetic retinopathy. Regardless of how it's achieved. So expect some noise in generalized data.
Personally, I went from mild background retinopathy to PDR and getting laser treatment in about 3 months. My ophthalmologist (who has an academic background) didn't really know if this diagnosis had the same "quality" of someone who "naturally" progresses to PDR, but some studies say it's transient.
By phantasmish 2025-11-1220:411 reply A lot of the issues are hydration-related, and I wouldn’t be surprised if the eye ones are, too. Some water intake is from food, so if you eat less, you need to drink more. If you also tend to drink with food, and you’re eating less, you may drink less instead of the more that you need to be. Add in a generally dulled “I crave something” sense and you’ve got a recipe for not just going all day without eating, but also without drinking.
By mock-possum 2025-11-1316:30 I’m not a doctor but iirc water consumed along with a meal is absorbed slower and therefore results in longer-lasting hydration - than just a bare glass of water on an empty stomach. Of course, eating might add more material that encourages dehydrating, so I don’t know if you’d get a net benefit from a bag of teriyaki beef jerky say.
By projektfu 2025-11-1317:58 It's a little suspicious... 68x risk with semaglutide, no significant risk with tirzepatide. Case-control studies that merely search these databases are only really useful for hypothesis generation.
GLP-1s have been peescribed for like 20 years, but have been limited more to diabetics and extreme cases. So there is pretty good data. Not to say there isnt going to be side effects in some population sample, but we need to compare that with obesity and diabetes (which is a very bad disease).
By Cthulhu_ 2025-11-1310:06 But also do long-term studies; one thing I gathered (anecdotal through the internet so take it with a grain of salt) is that people revert to their old habits when they stop taking it. Not always, of course, and I think using it should always be done with guidance of a dietician etc to make lifestyle adjustments if needs be, but it did imply that long term usage is a factor that needs to be considered.
By hollerith 2025-11-1316:16 SSRIs have been prescribed for 37 years, and society is just starting to understand that under current prescribing protocols, they do more harm than good.
Also, isn't the dose used to treat obesity 3 times higher than the dose used over those 20 years to treat diabetes?
By unsupp0rted 2025-11-1220:423 reply Not everything has another shoe to drop.
Getting people to eat more broccoli is almost entirely upside. Sure a handful of people will be allergic or whatever, but on a population level some interventions are just one positive after another, and there's no reason it has to be a deal made with the devil.
Well glp1 doesn't make you want to eat broccoli. Just less in general
By rootusrootus 2025-11-1222:032 reply Actually there is a very real effect on which foods you find appealing and which ones are kind of gross. It’s a thing the food companies have been studying, and their own studies show that people on GLP1s tend to skip the junk food aisle and head towards the produce section instead.
By 01100011 2025-11-137:18 Oddly enough semaglutide is making me crave sugar more. It might be the frequent sensation of having low blood sugar. Idk.
It does make me choose more dense meals though since I know I can't eat that much due to delayed gastric emptying. But I have to budget some room for prunes to counteract the constipation. It definitely makes you think about what you eat.
By skissane 2025-11-1319:20 Tirzepatide somehow gave me a craving for apples. I used to occasionally eat them, now I eat them every day.
sure but it definitely makes carbs specifically disgusting in my case
I can confirm that. On GLP-1s (when they worked for me, anyway), I'd routinely think "pizza? Bleh, so fatty, I'd really like some chicken breast with roast potatoes instead right now".
You can confirm that GLP1s make "carbs specifically disgusting" and an example of this reaction is that you would have a desire to eat potatoes?
Oh no, you have torn through the flaws in my argument like bullets through paper, however will I live this down? Unless I clearly meant "it makes previously-desirable food undesirable", anyway.
I was not trying to tear your argument down. The comment you replied to was about carbs being specifically disgusting and in my head potatoes are the runner up to bread for classic examples of carbs. I was simply asking about what seemed like a contradiction. I have been looking into GLP1s and have not seen/heard people mention that GLP1 make carbs gross.
By stavros 2025-11-1312:22 I think it varies per person. For me, it didn't specifically make carbs gross, but it did make unhealthy food less palatable. I think that's what the GP was talking about as well, they were just a bit more specific.
It really depends on the person, though. They worked for me for a while and don't work now, but I'm a small minority, from what I've heard from people. When they worked, they were great.
By Libidinalecon 2025-11-1323:27 It is really hard to compare broccoli to a powerful, rather new peptide that causes profound behavioral changes.
Usually you don't get a free lunch with such a compound.
By CalRobert 2025-11-139:44 I do get a bit gassy if I binge on broccoli…
Even with an increased risk of mortality, at least right now I can live. The voice in my head that is constantly telling me I'm hungry is quiet.
Without it I'd die sooner anyway.
It's not even "I'm hungry", it's just "must have more food". What a nuisance.
By rootusrootus 2025-11-1222:061 reply Exactly. Food noise is a terrible nuisance. “Go eat.” “Umm, I don’t feel hungry.” “Doesn’t matter, eat anyway.”
Having that on a repeat loop is no fun. Getting rid of it is worth all of the mild side effects and cost.
By stavros 2025-11-1222:09 100% agreed. It would be nice if I lost some weight, but just not having the food noise is worth it.
By toomuchtodo 2025-11-1221:003 reply Many Americans drive a car every day, even though ~40k people a year die in car accidents. Why? Because the benefits outweigh the risk.
(my partner is on a GLP-1, and lost ~25 lbs in 3 months)
> Why? Because the benefits outweigh the risk
Many of us wish we didn't have to drive a car. Many of us also wish we didn't live in a world where hyperprocessed foods weren't the norm
By toomuchtodo 2025-11-1314:15 Agreed, but we must operate and decision in the world we live in, not the world we wish we lived in.
> Many Americans drive a car every da
Coincidentally also a factor of why many Americans take GLP-1 frugs
By chrisco255 2025-11-139:503 reply Not really, Americans have been driving cars for over 100 years but the obesity epidemic cropped up in the last 30 years.
By dredmorbius 2025-11-143:54 The automobile's net effect on behaviours has (as others have noted) evolved over that period, as has its net effect on transportation and urbanisation patterns.
Up until the end of WWII, automobile ownership was relatively limited. It was just beginning to accelerate at the beginning of the war (in the US), but rationing and war-time defence manufacturing curbed that trend, and sustained rates of alternative transport, particularly rail.
Post-war, there was a mass-consumer blitz, much of it revolving around automobiles, and changes such as commuter suburbs (based around automobiles), superhighways, self-service grocery stores, shopping malls, and strip-mall based retail development began, all trends which evolved over the next 50+ years.
In the 1970s and 1980s, it was quite common for children to walk or ride bikes to school, or take a school bus (which involved walking several blocks to a nearby stop). Since the late 1990s, far more seem to be ferried in private cars, usually by parents, who spend a half-hour or more in pick-up lines. It's not uncommon for children walking along neighbourhood streets to be reported (and collected) by authorities by concern for their safety, and their parents subject to investigation or worse. Suburban, and even urban development patterns have been to ever-lower-density and far more bike- and pedstrian-unfriendly modes.
Recreational, occupational, educational, and other transport and activity patterns are largely away from self-powered movement (walking, cycling, etc.) and toward motorised options (sometimes including e-bikes, electric scooters, or equivalents, though most often automobiles).
Societal change and consequent impacts take time and have long lags.
By atherton94027 2025-11-1313:51 Per-capita volume of miles traveled went up by 5x since 1950: https://enotrans.org/article/americans-drove-1-0-percent-mor...
By WithinReason 2025-11-1314:42 It's still a factor
By kshahkshah 2025-11-1315:01 I’m a huge proponent of GLP’s, but with respect to cars I would say that the privatized incentives outweigh the risk to the public
By infecto 2025-11-1220:28 I don’t know. Having listened to a number of interviews with some of the founders in this area of drug research I came away with a much higher respect and significantly less cynicism toward big pharmaceutical. Novo Nordisk is run by a nonprofit even.
By DharmaPolice 2025-11-1221:09 I'm sure there will be negative side effects but the main outcome of these drugs is that you eat less. Many of us have trained ourselves to eat at a frequency and volume way beyond what is really required to keep our body functioning. This leads to weight gain in most people and thus is the focus but even independent of weight there are effects of continuously eating poor quality foods which are unlikely to be good. So I'm not surprised that there are all these miraculous sounding positive side effects to drugs which prevent most people from putting their metabolic system under near constant load.
When the side effects are better understood I suspect for the average person, eating less would be a net benefit to their overall health - _even if they don't lose any weight_.
By coffeebeqn 2025-11-1221:18 I’m sure some negative effects will be found but from what I understand lowering your weight outweighs (no pun intended) a lot of possible side effects. Closest thing to a miracle cure and quality of life improvement
Haven't you been reading Hackernews for the past 10 years? Sugar has been implicated in pretty much every major late-life disease, and the closest thing to a cure before GLP-1 agonists was fasting.
By phantasmish 2025-11-1220:32 … and the mechanism by which GLP-1s cause weight loss is, more or less, by making fasting really easy.
By pessimizer 2025-11-1220:51 Hacker News has extreme orthorexia and endorses all sorts of quackery.
That's such a lazy and unimaginative take that basically skips 99.999% of human history during which sugar wasn't a problem at all.
By tengbretson 2025-11-1221:16 The baseline lifestyle of 99.999% of human history would, by modern classifications, be considered intermittent fasting.
By ThePowerOfFuet 2025-11-1523:111 reply Refined sugar hasn't been a problem for 99.999% of human history because it hasn't existed for 99.999% of human history.
By jimbokun 2025-11-1221:26 That was the part of history when humans didn’t have much access to cheap sugar.
By Der_Einzige 2025-11-1316:12 You’re the lazy one.
I am sort of in your boat in seeing what may come. There are a few very rare conditions but the benefits seem to out weigh (ha, I will take the pun!) The down sides.
While it might mean the incident rare of some things goes up, those that it reduces are far more impactful and where far more likely to have mortality issues. Sort of like how Chemotherapy is poisonous but potential has better long term odds, only chemo is far more extreme than GPL1.
Time will tell but so far it is looking kind of good with a few lesser issues.
By CoastalCoder 2025-11-1315:20 > chemo is far more extreme than GPL1.
Which is ironic because someone at Microsoft once called the GPL "cancer".
Basically, the gastro-intestinal side effects are the biggest issue, along with CVS (not the store) and possibly eye problems.
That said, the negative side effects look to be incredibly rare and manageable (including via stopping treatment) -- and the positives are quite tremendous.
It's not a magic drug, but it is the first of it's kind with such a skew to the positive on side effects.
By brazukadev 2025-11-1317:21 > It's not a magic drug
It actually is a magic drug. The same way ultra-palatable food is also not natural.
By 45764986 2025-11-1221:54 These drugs have been around for more than 10 years. If there were significant downsides, we probably would have seen them already.
By radial_symmetry 2025-11-1220:343 reply Most medications have negative side effects because otherwise our bodies would already have whatever changes they make through evolution. My personal theory (based on nothing but my own intuition) is that GLP-1s are an adaptation to the modern world that evolution hasn't caught up with yet.
By ammon 2025-11-1220:40 And we know what the adaptation is: calorie constraint. We evolved in a calorie constrained environment. We don't live in one now. Our set point for desire to eat is clearly too high. None of this means that glp-1 inhibitors don't have other side effects, of course.
> Most medications have negative side effects because otherwise our bodies would already have whatever changes they make through evolution.
That's not what evolution is, at all
By dillydogg 2025-11-1312:13 This sounds like the argument during the pandemic, "If masks work, then why didn't we evolve permanent masks? Checkmate atheists." Though I do understand the impulse that evolution is working towards some unknowable perfection because of how I was taught evolution during high school, that is, of course, not how it works.
By viking123 2025-11-135:18 lol
By bossyTeacher 2025-11-1221:541 reply Given all the potential money, if they are issues, I expect it to go down like tobacco companies back in the days actively suppressing undesirable research by harassing researchers, influencing peer review journals or/and funding research casting doubt on the benefits of this drug. Chances are that any negative effects won't be obvious until it's too late. Look at microplastics, they have been around for just over a century and it's only now that we are starting to realize that they have several negative effects.
By CoastalCoder 2025-11-1315:33 I agree. I think it's unlikely that negative effects can go unnoticed for very long, but in the short term I'm only like 97% sure we're getting the full story.
That said, it's probably certain enough for me to be open enough to using them now, if my doctor recommends it.
Several members of my family are into glp-1 both for glucose control and for weight loss. Taking different brands (wegovy, ozempic and others.) They all mention.th terrible secondary effects when you eat something "forbidden" (tacos, cake or icecream e.g.) .
Also It causes constipation apparently, which for most of them is not that much of an issue, but given that I've IBS-C, I'm happy to not have to take it.By CoastalCoder 2025-11-1315:23 I'm surprised that tacos are a big deal. I'd have thought that the filling (meat, cheese, veggies, maybe beans) would mostly outweigh the carbs from the shell.
I take a glp-1 and suffer no ill effects when I eat something "forbidden".
By icebergonfire 2025-11-139:46 More anecdata, my spouse and I have been on Mounjaro since Jan 2025 guided by private health insurance.
I have suffered almost the entire gamut of side effects from the beginning until I tried split dosing twice a week, and even then there’s still the occasional instance of me learning that I should not have eaten that and the following 9 hours are going to revolve around stomach pain.
My partner’s journey on the other hand has been smooth sailing the entire time.
YMMV, do your own research but definitely double check any search results with your doctor first… lots of urban myths going around.
I do recommend it though, I am the healthiest I’ve been in literally 10 years.
By 01100011 2025-11-137:15 I was in that boat too but with NAFLD and now liver fibrosis despite not eating all that much sugar and having a BMI that is high but partially due to muscle I finally gave in to see if semaglutide will help.
Only on week 3 but it's been a rollercoaster. It seems to have quite a broad spectrum of effects. I'm still not sure I'll be able to stay on it but losing 10 pounds is a nice counterpoint to the side-effects.
By piker 2025-11-1220:30 The fact is though that but-for taking the drugs a lot of the folks that take these things would be long dead before, say, the GLP-1 induced cancer kicked in.
By JumpCrisscross 2025-11-1221:071 reply > I'm waiting for the other shoe to drop when it comes to GLP-1s
We know there are downsides. They’re just irrelevant compared to being obese. (Or alcoholic. Or, potentially, overweight.)
It might be a vitamin, where there literally aren’t any downsides. I’m sceptical of that. But to the degree there is mass cognitive bias in respect of GLP-1s, it’s against them. (I suspect these are sour grapes due to the drugs being unreachable for many.)
My frank concern is we’re separating into a social media addicted, unvaccinated and obese population on one hand and a wealthy, insured, disease free and fit one on the other. Those are dangerous class and physical divides to risk becoming heritable (socially, not genetically).
By zemvpferreira 2025-11-1221:311 reply GLP-1’s should make you less concerned in that case, they’re poised to become extremely affordable very soon. Ending the obesity epidemic will do more to bridge the class divide than anything I can practically imagine. Not to mention the other compulsions these drugs help moderate - alcohol, tobacco, gambling etc. It’s my best hope for worldwide quality of life improvement in the next 10 years.
By JumpCrisscross 2025-11-1221:571 reply > Ending the obesity epidemic will do more to bridge the class divide
My hope is the "waiting for the other shoe to drop" folks are just expressing sour grapes.
If it runs deeper and merges with the anti-vaxers, we've got a behavioural problem fuelling a class divide. That is my fear.
By phil21 2025-11-135:21 I’ve thought about this a decent amount.
My opinion has shifted over the years. At first I also thought it was largely just sour grapes re: accessibility and fear of the unknown, but now I’m thinking that a large number of people are going to be so far deep into anti-GLP opinions and hot takes they can’t backtrack out of it. Much like political or social beliefs you make into your identity. Too embarrassing to admit you might be wrong.
I know you’re alluding to the same thing, it’s just interesting to me someone else in the world seems to share these thoughts. I also think it may really delineate a multi-generational class divide that is hard to break.
Or all the folks on GLP-1s will develop some rare form of cancer and die early leaving the world to the so-called haters.
By thefz 2025-11-136:45 > Maybe I'm just an aging cynic, but I'm waiting for the other shoe to drop when it comes to GLP-1s. There have been so many claims of positive benefits that it almost seems too good to be true.
Well, read up the testimony of those who stopped taking it for adverse effects, such as nonexistent intestinal transit and -yuck- sulfur burps.
Its not upside per se, more like avoiding the downsides of diabetes and obesity.
Healthy, non-obese individuals likely aren't seeing these "benefits"... But I'm not a doctor, I just pretend to be one on the Internet.
This isn't true, the heart and kidney benefits appear independent of weight loss. I would encourage you to let the physicians speak to these effects instead of making educated conjecture; it is tough to keep ahead of all of the claims about these medications with my patients.
By bpodgursky 2025-11-1220:281 reply GLP-1s are just showing what people always knew to be true but was not clinically actionable — most of our health problems come from eating too much and being fat.
Well, now it's actionable. No magic, just adherence.
By degamad 2025-11-1221:06 We don't quite have the data to say "most" yet, but it's certainly looking like "many" is justifiable.
By ilikecakeandpie 2025-11-1221:112 reply Yeah I stopped because I didn't like the way it made me feel. I needed it because my blood sugar was way too high and it helped me drop close to 60 pounds in 6-8 months, but I did not like how it made me feel and I lost more muscle than I was happy with.
I've gained about 15-20 pounds back, but I'm now much healthier overall.
I like how my brain works and I didn't like something affecting or changing that because I couldn't put the fork down. Easy decision for me
By AndrewDucker 2025-11-1221:39 I'd be interested to know how it changed you.
By CoastalCoder 2025-11-1315:261 reply Is it possible that some of that personality change was because you were running a calorie deficit?
I'm not dismissing your overall point. I minimize my use of Adderall for that very reason.
By ilikecakeandpie 2025-11-1718:02 Maybe? I don't think so though. I may have written incorrectly because my personality itself did not change, but it was a massive change seeing eating and drinking remarkably smaller amounts of stuff and I knew it was because of the drug slowing down my digestion. I'd rather have my agency to make mistakes and maybe eat half a pizza when I want to instead of finishing a slice and feeling queasy at the thought of a second one.
By matthewdgreen 2025-11-1221:07 Say more?
By helicalmix 2025-11-1220:29 I think it's totally fair to be skeptical, but it's also not rare to have interventions that are astoundingly effective.
Antibiotics and vaccines may not be completely free lunches, but they're very good at what they do.
By Der_Einzige 2025-11-1316:091 reply This kind of “it’s too good so it must be bad” thinking is a cancer in our species.
By hollerith 2025-11-1316:12 I agree. A better response is, "maybe GLP-1 drugs are really great or maybe the drug companies, which spend most of their time and money trying to manipulate opinion (i.e., by bribing researchers and clinicians, which is not illegal) are at it again."
By gedy 2025-11-1220:40 At this point I view the risks/downsides as akin to vaccines. Sure things happen, the overwhelming positives greatly outweigh this.
By MangoToupe 2025-11-135:05 Hey some of us struggle to eat enough and/or remember to eat in the first place
By mannanj 2025-11-1312:31 Right. This is what we heard about the COVID therapies. And we all know how that turned out to be little more effective than placebo for healthy non-comorbid people.
By jesse_dot_id 2025-11-1220:511 reply Same. I think that pharmaceutical industry is lot more bleak now than it was when Fen-Phen became popular. GLP-1 usage is largely off-label as far as I know, but I wouldn't trust them even if it wasn't. There is a mountain of precedent for these companies to choose profit over health, and for our government(s) to aid them in covering up evidence of negative effects on the latter for the sake of the former.
By topato 2025-11-1221:27 The popularity of these drugs is specifically from the FDA-approved "weight loss" indication. You're at least a few years behind. I would also think the many many years when it was only prescribed for diabetes would have yielded some data about negative effects, (other than the ocular issue) if there were any. Glp-1s were so unprofitable, Novo Nordisk let their Canadian patent lapse almost a decade ago, rather than pay the upkeep fee lol. So I dont think anyone is protecting them from bad press.
