GLP-1 drugs linked to lower death rates in colon cancer patients

https://today.ucsd.edu/story/glp-1-drugs-linked-to-dramatically-lower-death-rates-in-colon-cancer-patients

241•gmays•2mo ago

Comments

bicx•2mo ago

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.

bitwize•2mo ago

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.

phantasmish•2mo ago

… and the mechanism by which GLP-1s cause weight loss is, more or less, by making fasting really easy.

lm28469•2mo ago

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.

tengbretson•2mo ago

The baseline lifestyle of 99.999% of human history would, by modern classifications, be considered intermittent fasting.

jimbokun•2mo ago

That was the part of history when humans didn’t have much access to cheap sugar.

Der_Einzige•2mo ago

You’re the lazy one.

ThePowerOfFuet•2mo ago

Refined sugar hasn't been a problem for 99.999% of human history because it hasn't existed for 99.999% of human history.

pessimizer•2mo ago

Hacker News has extreme orthorexia and endorses all sorts of quackery.

robbomacrae•2mo ago

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...

phantasmish•2mo ago

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.

mock-possum•2mo ago

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.

azinman2•2mo ago

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.

robbomacrae•2mo ago

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.

azinman2•2mo ago

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.

asmor•2mo ago

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.

projektfu•2mo ago

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.

bpodgursky•2mo ago

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.

degamad•2mo ago

We don't quite have the data to say "most" yet, but it's certainly looking like "many" is justifiable.

infecto•2mo ago

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.

gwbas1c•2mo ago

Some people stop using it due to personality changes.

matthewdgreen•2mo ago

Say more?

ilikecakeandpie•2mo ago

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

AndrewDucker•2mo ago

I'd be interested to know how it changed you.

CoastalCoder•2mo ago

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.

ilikecakeandpie•2mo ago

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.

helicalmix•2mo ago

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.

piker•2mo ago

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.

ecshafer•2mo ago

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).

Cthulhu_•2mo ago

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.

hollerith•2mo ago

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?

OptionOfT•2mo ago

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.

stavros•2mo ago

It's not even "I'm hungry", it's just "must have more food". What a nuisance.

rootusrootus•2mo ago

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.

stavros•2mo ago

100% agreed. It would be nice if I lost some weight, but just not having the food noise is worth it.

radial_symmetry•2mo ago

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.

ammon•2mo ago

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.

lm28469•2mo ago

> 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

dillydogg•2mo ago

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.

viking123•2mo ago

lol

gedy•2mo ago

At this point I view the risks/downsides as akin to vaccines. Sure things happen, the overwhelming positives greatly outweigh this.

unsupp0rted•2mo ago

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.

cerved•2mo ago

Well glp1 doesn't make you want to eat broccoli. Just less in general

daedrdev•2mo ago

sure but it definitely makes carbs specifically disgusting in my case

stavros•2mo ago

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".

dfc•2mo ago

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?

stavros•2mo ago

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.

dfc•2mo ago

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.

stavros•2mo ago

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.

rootusrootus•2mo ago

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.

01100011•2mo ago

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.

skissane•2mo ago

Tirzepatide somehow gave me a craving for apples. I used to occasionally eat them, now I eat them every day.

CalRobert•2mo ago

I do get a bit gassy if I binge on broccoli…

Libidinalecon•2mo ago

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.

jesse_dot_id•2mo ago

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.

topato•2mo ago

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.

CyanLite2•2mo ago

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.

dillydogg•2mo ago

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.

https://www.science.org/doi/10.1126/science.adn4128

toomuchtodo•2mo ago

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)

culi•2mo ago

> 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

toomuchtodo•2mo ago

Agreed, but we must operate and decision in the world we live in, not the world we wish we lived in.

thefz•2mo ago

> Many Americans drive a car every da

Coincidentally also a factor of why many Americans take GLP-1 frugs

chrisco255•2mo ago

Not really, Americans have been driving cars for over 100 years but the obesity epidemic cropped up in the last 30 years.

atherton94027•2mo ago

Per-capita volume of miles traveled went up by 5x since 1950: https://enotrans.org/article/americans-drove-1-0-percent-mor...

WithinReason•2mo ago

It's still a factor

dredmorbius•2mo ago

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.

kshahkshah•2mo ago

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

JumpCrisscross•2mo ago

> 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).

zemvpferreira•2mo ago

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.

JumpCrisscross•2mo ago

> 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.

phil21•2mo ago

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.

DharmaPolice•2mo ago

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_.

coffeebeqn•2mo ago

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

45764986•2mo ago

These drugs have been around for more than 10 years. If there were significant downsides, we probably would have seen them already.

bossyTeacher•2mo ago

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.

CoastalCoder•2mo ago

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.

xtracto•2mo ago

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.

tssva•2mo ago

I take a glp-1 and suffer no ill effects when I eat something "forbidden".

icebergonfire•2mo ago

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.

CoastalCoder•2mo ago

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.

m463•2mo ago

I wonder if you could ask: are there downsides to losing weight?

MangoToupe•2mo ago

Hey some of us struggle to eat enough and/or remember to eat in the first place

PeaceTed•2mo ago

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.

CoastalCoder•2mo ago

> chemo is far more extreme than GPL1.

Which is ironic because someone at Microsoft once called the GPL "cancer".

thefz•2mo ago

> 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.

01100011•2mo ago

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.

mannanj•2mo ago

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.

glp1guide•2mo ago

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.

brazukadev•2mo ago

> It's not a magic drug

It actually is a magic drug. The same way ultra-palatable food is also not natural.

Der_Einzige•2mo ago

This kind of “it’s too good so it must be bad” thinking is a cancer in our species.

hollerith•2mo ago

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."

agentifysh•2mo ago

is there an extract or can you get it from natural food? which have it ?

phantasmish•2mo ago

GLP-1 agonists? Well they derived them from a lizard, so, uh… sort of? But no, no foods you eat are really going to have GLP-1 agonists in them, not to any meaningful degree anyway. Plus if you’re eating them they have to survive at least part of the digestive tract, which means you need even more since some of it’ll be lost.

Your body produces GLP-1, but it lives in the blood for like minutes. The innovation was finding a chemical that tickles the same receptors but survives in the body for days at a time.

cstrahan•2mo ago

There may be some herbal supplements that impact GLP-1 release to some extent, but what is being talked about here are synthetic GLP-1 receptor agonists.

mrtesthah•2mo ago

https://www.sciencedirect.com/science/article/pii/S221112471...

L-tryptophan > Indole > Raises GLP-1

fleetwood•2mo ago

Resistant starch https://pmc.ncbi.nlm.nih.gov/articles/PMC10085630/ https://pmc.ncbi.nlm.nih.gov/articles/PMC4030412/

ck2•2mo ago

no GLP-1 generics until 2030

lots of people will miss out on benefits, like oh preventing death

our drug system is weird

exabrial•2mo ago

Private people invested a lot of money to develop this and get it through testing. Allowing them to reap the benefits from their investment for a limited time is just fine.

It's not people couldn't also: Diet, exercise, choose veggies, eat more fiber, etc

isoprophlex•2mo ago

"Sorry bro gonna let you die because, muh investments, you see"

Your closing remark is overly simplistic and offers a contradiction: if those things would work for these obese people, they wouldn't need GLPs.

exabrial•2mo ago

The laws of thermodynamics apply to everyone equally.

asdff•2mo ago

Where in thermodynamic principles does it suggest money ought to flow into the pockets of the few?

phantasmish•2mo ago

The standard for medical interventions usually isn’t “could it work?” or “should it work?” but “does it work?”

This is why the efficacy of every single contraceptive method isn’t way higher than it is. Lots of them should work almost perfectly… but the harder they are to use correctly, the less effective they in-fact are.

exabrial•2mo ago

Eating less, exercising more, has worked for the entire existence of human race. In fact, it worked for me just fine too. GLP-1s are a safe and proven tool and should be used wherever appropriate to assist people. Both of these are simple facts that aren't in contradiction with either other.

But saying the patent owners shouldn't be allowed to reap the benefits of their investment is ridiculous, especially when it's completely possible to lose weight in other ways. 6 years isn't that long to wait anyway.

ck2•2mo ago

just want to point out it's not just for obesity

GLP-1 has been demonstrated to even cure some types of long-covid in some people in some cases

and various other diseases

but it's priced way out of reach even for micro-doses until it becomes generic

so all those cases suffer until 2030, if they make it that far, five years is a long time

asdff•2mo ago

The public also invested a lot of money.

cess11•2mo ago

Kind of weird to assume other people think it's fine to exchange human lives for money.

Is it ethical for me to pay someone to murder you? Does it matter if it costs me a large amount of money or not?

exabrial•2mo ago

This is a great example of a straw-man attack.

cess11•2mo ago

No, it is not. They said that since someone, which is typically a fictive person, had spent a lot of money, they deserve to restrict physical persons' access to supposedly life saving substances.

I would like to know how far they take that position.

WillPostForFood•2mo ago

How many people do you feel liek you are personally responsible for killing because you haven't given 100% of your disposal income to food relief? Hundreds? Thousands?

CobrastanJorji•2mo ago

This isn't "I could use my money to acquire food for the poor." It's "I'm going to prevent anyone else from selling food, and that will let me charge 100x as much for food."

cman1444•2mo ago

And yet, if the system wasn't set up this way it's likely that these medicines would never have been developed in the first place.

If we take away investor returns now, why would they ever pursue developing similarly effective drugs in the future?

cess11•2mo ago

On the contrary, profit motive and immaterial rights slow down innovation and the spread of new technologies.

This is why states are the main producers of knowledge and funding most of the interesting research.

CobrastanJorji•2mo ago

Good point, maybe researching drugs and treatments shouldn't be done primarily by for-profit companies, and governments should take this on themselves.

ashdksnndck•2mo ago

Why do we pay doctors? Are they evil if they refuse to go to work for free?

cess11•2mo ago

Please explain the relevance of this supposed analogy. How is a doctor withholding their labour restricting the behaviour of anyone else?

ashdksnndck•2mo ago

People spend their time and resources developing drugs because they know that the patent system provides them an opportunity to earn a return. If drug patents weren’t enforced, GLP-1 would have never been developed. We could rug-pull the particular companies who own GLP-1 patents by removing patent protection after the fact, that would work to improve access to these particular drugs. But then the next lifesaving drugs won’t be developed, because there will be no prospect for a return.

Similar to how doctors save lives and earn a paycheck. We could stop paying doctors, enslave them to work 18 hours 7 days a week so more people get medical care. On top of being obviously evil and wrong, it would also be counterproductive, because then nobody would become a doctor.

Put simply, drugs cost money because money is how we direct resources as a society. There is not a cheat code where we can simply make the drugs free and still expect resources to magically appear and manifest the drugs. The drugs exist because we pay for them.

I share the feeling that it’s awful that people are blocked from access to these lifesaving drugs by money. But simply eliminating patent protection is not a workable solution. It needs to be accompanied by a replacement mechanism to incentivize drug development. For example, government gives out massive prizes to the drug developer but there is no patent protection.

k_roy•2mo ago

Protecting it before generic is fine, but the pricing doesn't make sense.

If it's $1000 per month cost per person when it's the name brand, how many people are on it? At this point just the diabetics and people with really good insurance?

Wouldn't they make a hell of a lot more money selling it for $100 during their protected period to 1000x the people.

kube-system•2mo ago

They have direct discount programs where they sell at ~ half price.

pretzellogician•2mo ago

True, but also still absurdly high. Novo Nordisk and Eli Lilly cost roughly $500 monthly... but the price is almost the same regardless of the dosage (from say 0.5mg to 2.4mg).

MangoToupe•2mo ago

> Allowing them to reap the benefits from their investment for a limited time is just fine.

Or we could just move to a sane economic system where we don't have to beg the rich/reward people for having money

km144•2mo ago

Those things also require more willpower than taking a medication. Willpower is generally determined by your particular psychology which is determined by genetics and environmental factors. People don't have a choice in the matter as much as your comment seems to imply. Getting GLP-1s to everyone who could benefit from them is extremely important for overall health.

mrtesthah•2mo ago

In theory you could supplement with L-tryptophan which is metabolized into indole which then raises GLP-1 production within enteroendocrine cells.

https://www.sciencedirect.com/science/article/pii/S221112471...

matthewdgreen•2mo ago

Or anything that boosts Akkermanskia.

Bender•2mo ago

I use that to help me stay asleep. I also feed large amounts of it to horses and deer before, during and after 4th of July since everyone here launches mortars from their fields. Helps them chill.

degamad•2mo ago

It's not obvious that there is a benefit here - the third sentence of the summary at the top says:

> Indole increased GLP-1 release during short exposures, but it reduced secretion over longer periods.

kube-system•2mo ago

Compounded GLP-1s are still floating around in the US

ck2•2mo ago

if you saw the 60 Minutes on compounding pharmacies, which are completely unregulated and never inspected, and sometimes contaminate products out of lack of care/repercussions

you'd never touch a compounded pharmacy product ever again

people have died from contamination

kube-system•2mo ago

Compounding pharmacies are regulated by section 503 of the FD&C act, and also subject to inspection.

Are you referring to the fact that the FDA does not inspect all facilities because they have limited resources? This applies to pharmaceutical companies as much as it does to compounders. If you think the FDA posts inspectors at every pharmaceutical company in India, you’d be wrong.

ACCount37•2mo ago

People are straight up buying black market "research use only, not to be used in humans" GLP-1. Compounding pharmacies are reliable, safe and well regulated compared to that.

Clearly, there's an entire spectrum of tradeoffs between safety/shadiness, availability and price. I think that's a good thing.

kshahkshah•2mo ago

I compound tirz with glycine and B12. I honestly think these are miracle drugs.

I’ve never been extremely overweight but I hit a point where I had 30 pounds to lose, despite my height, and I can’t deal with the hunger amidst all my other life stresses.

crowbahr•2mo ago

In a similar boat (overweight, borderline obese - slightly elevated cholesterol - high stress) and my doc has recommended I look into GLP-1s and maybe ask my insurance which types they do and don't cover.

Worst comes to worst I could go compounding for about $200/mo from what I've seen.

pretzellogician•2mo ago

There are already GLP-1 generics available like liraglutide; they're just not as effective as the newer ones.

(This refers to the U.S. Some other countries have more generics available.)

glp1guide•2mo ago

Like others have mentioned, liraglutide already exists as a generic! It's not as good as Semaglutide or Tirzepatide, but.

Also, a lot of people are still getting compounded GLP1, to the chagrin of Eli Lilly and Novo Nordisk.

Separately, 2026 is about to completely change the pricing of this stuff, not even taking into account the Trump administration's recent efforts. The price of injected GLP1 is going to implode due to patents lapsing in Canada and other places -- and for the pill forms that come out soon it looks like the Trump administration is keen on keeping prices for that low as well.

jl6•2mo ago

> 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.

stavros•2mo ago

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?

ed•2mo ago

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.

rickydroll•2mo ago

They also help with slowing the progression of CKD

https://www.kidneyfund.org/treatments/medicines-kidney-disea...

anovikov•2mo ago

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?

stavros•2mo ago

Because they lose weight and it's too dangerous.

anovikov•2mo ago

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.

cyrusradfar•2mo ago

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.

trallnag•2mo ago

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.

amenhotep•2mo ago

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.

cyrusradfar•2mo ago

Appreciate the thoughtful retort. Have a good one.

trallnag•2mo ago

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.

mock-possum•2mo ago

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)

itchyouch•2mo ago

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.

asmor•2mo ago

(Outer) Thigh, upper arms and stomach are the on-label injection sites for these drugs.

ifwinterco•2mo ago

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

avgDev•2mo ago

Pseudoscience scares me. There are so many people that believe this nonsense and basic understanding of medicine disproves many of those claims.

op00to•2mo ago

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.

itchyouch•2mo ago

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.

itchyouch•2mo ago

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.

floor2•2mo ago

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".

gavinray•2mo ago

  > 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.

Thanks for the dumbest thing I've read all day

l5870uoo9y•2mo ago

There is no such thing as water fasting. I would characterize it as an eating disorder.

cyrusradfar•2mo ago

Umm.

Sources?

  - https://en.wikipedia.org/wiki/Fasting
  - https://zerolongevity.com/blog/the-history-of-fasting/

InMice•2mo ago

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.

l5870uoo9y•2mo ago

Took "water fasting" to mean fasting even without water, apparently it is the opposite.

InMice•2mo ago

LOL total misunderstanding then. No problem.

Cthulhu_•2mo ago

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.

foobarian•2mo ago

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.

codr7•2mo ago

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.

dredmorbius•2mo ago

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.

codr7•2mo ago

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.

InMice•2mo ago

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.

lazyasciiart•2mo ago

If you include as much meta-commentary every time, you’re certainly going to get downvoted.

dredmorbius•2mo ago

<https://news.ycombinator.com/item?id=9562917>

Just make your point, as clearly and persuasively as possible.

codr7•2mo ago

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.

p00dles•2mo ago

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/...

mr_luc•2mo ago

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?

freetime2•2mo ago

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.

andy_ppp•2mo ago

If you eat less your stomach/whole body gets time to relax and repair?

pedalpete•2mo ago

My understanding is that it slows the digestive process, so there isn't more "empty time to repair or relax".

But my thinking there may be naive.

andy_ppp•2mo ago

I just know someone who skips breakfast and lunch on the jabs… maybe he eats dinner I’ve not checked.

icebergonfire•2mo ago

Anecdotally speaking I can confirm this… it gets easy to just skip a meal, and you may end up skipping the entire day because the usual hunger signals are just not there.

For anyone tempted by that concept, please don’t and remember to try to eat your 1000-1500 calories every day.

Quick weight loss won’t do you any good if you lose all your muscle mass, or if you carve a deeper groove into body image issues.

It’s cliche but it’s true, slow and steady is the way to go.

glp1guide•2mo ago

At this point most experts lean more heavily on the effect of GLP1s in the brain rather than delayed gastric emptying -- it's more of a brain drug than anything else which is why it works so well.

foxyv•2mo ago

Beware of intuitive conclusions. (AKA: Truthiness) It's easy to believe something because it sounds true but still be completely wrong.

https://www.merriam-webster.com/dictionary/truthiness

Noaidi•2mo ago

I do not like the framing. GLP-1 drugs help people lose weight, and it is the weight loss that lowers death rates in colon cancer[1]. This is making it sound like the drug itself is reducing cancer.

[1] https://link.springer.com/article/10.1007/s12672-025-03902-4

surfsvammel•2mo ago

I don’t agree. They are not saying that.

It’s observational. They are saying they see correlation.

Your suggested mechanism is plausible, and likely, of course, but that might only be part of the effect.

I think it’s still valuable findings and can help direct further studies.

dehrmann•2mo ago

Whether or not this is the case for this particular study, I wouldn't be surprised if they end up being miracle drugs that reduce everything from heart disease to liver disease to cancer through weight loss and reduced alcohol consumption.

surfsvammel•2mo ago

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.

richwater•2mo ago

Is there evidence for addiction tendencies in general? Or is it something specific to alcohol?

surfsvammel•2mo ago

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.

zemvpferreira•2mo ago

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.

SoftTalker•2mo ago

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.

toomuchtodo•2mo ago

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

CobrastanJorji•2mo ago

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.

donsupreme•2mo ago

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.

foobarian•2mo ago

Wonder if it would help compulsive gamblers then.

basisword•2mo ago

I think that’s already been shown (at the very least I’ve read news articles with anecdotes).

fgimenez•2mo ago

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.

hexbin010•2mo ago

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

Cthulhu_•2mo ago

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.

aswegs8•2mo ago

Does the very low dose help with weight management?

pretzellogician•2mo ago

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.

_1•2mo ago

Same. two drinks and I'm done

JumpCrisscross•2mo ago

Would you mind sharing what BMI you had when you started treatment and through whom you went? Curious about the low/micro dose effects.

basisword•2mo ago

I am 100% a layman here so apologies if this is a stupid analysis. But I have read that fasting can improve odds and improve side effects during chemo. Would GLP-1 stabilising blood sugar be having the same effect?

foxyv•2mo ago

I would hesitate to draw a conclusion without more evidence. One way or another.

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