The FDA will likely approve the diabetes drug tirzepatide for weight loss

I'm also one of those people who finds it more convenient to eat 1 meal per day when busy. It also started in my early 20s, but I've never been on stimulants. I got in the habit of eating irregularly in grad school which made it even easier to continue. I rarely have any appetite within an hour of waking up, and ive almost never eaten during this window. Not clear to me which is the cause vs effect.

I know some people who are on the opposite end and have problems functioning after missing lunch. None of them have ever intentionally fasted, though again it's hard to separate cause from effect.

What is clear is that different people's bodies form very different expectations surrounding food intake, and we are mostly unaware of this collectively.

No Adderall works via a completely different pathway.

Not at all, nor do all prescribed users of Adderall experience any change in appetite.

> Adderall increases the level of serotonin in your body, which can cause your appetite to decrease, leading to weight loss. This can be a good thing if you are trying to lose weight, but it can also cause stomach pain.

Low metabolism perhaps?

There's a lot we don't know, but from what I gather microbiome tends somewhat towards homeostasis such that you tend to eat in a way that maintains the current status quo. Among other things, this is linked to things like whether or not you are at risk for obesity.

I’m also on it, originally started it for weight loss, and am down 35lbs in 4 months. However I’m starting to wonder if I was diabetic or pre diabetic, as I no longer feel my blood sugar changing throughout the day.

The drug has been great, with minimal side effects. Simply not interested in food, and always feel full.

Does the coupon make it cost $25, or just reduce the cost by $25? Any other specifics on this would be super helpful!

As long as it doesn't damage those things by itself, either it will help them or we're totally wrong about what causes them.

Very likely so. I know of at least one study in which they are interested in determining if weight loss from semaglutide results in a similar decrease in cancer rates that they see in bariatric surgery patients.

The drugs cause you to eat less and the mechanism of the drug may, in and of itself have some cardio protective effects. To get a drug approved for diabetics, you have to demonstrate it doesn’t cause cardiovascular issues because the comorbidity among diabetics is so high, and other drugs have a history of helping with blood sugars but causing cardiovascular issues. On those measures, iirc, semaglutide specifically showed my that the treatment group saw a significant reduction in cardiovascular events. I’m on mobile so can’t provide links at the moment.

Dulaglutide is a drug in the same class that has been around longer there is a modest improvement for cardiovascular events.

5.4 years on the drug:

https://pubmed.ncbi.nlm.nih.gov/31189511/

This is a regressive opinion.

If we have tools available that can solve problems—as humans are not perfect—then why not use them? Do you not enjoy the benefits of other medicine that solves problems you have, like susceptibility to Covid?

We should always be on the conquest to improve our livelihoods. If that means introducing a drug to combat obesity so that scores of people can extend their lifespans by being healthier, that is a good thing.

Patients do indeed need the drug to keep the weight off. They have proven this. But that is not an issue at all. Individuals who have gained a significant amount of weight do not produce leptin, grehlin, and other related hormones in the same way that people at a normal weight do. Once you’ve put on a significant amount of weight you can’t just expand the size of your fat cells you make new cells entirely. Even if you remove those new cells via liposuction, the body recreates them as a homeostatic response. The result is that something like 10% of obese people that lose weight have kept it off two years later. The people who keep it off have been studied extensively as a group and generally they weigh themselves daily and many of them count calories meticulously. As soon as they stop doing that, they regain the weight. It’s a path dependent outcome. Once you’ve walked the path to obesity, your body fights you walking back towards healthy. This drug adjusts some of the same hormones that get out of whack when you’ve been overweight before. Unfortunately not all of them can be safely played with (giving people leptin and leptin like hormones tends to cause cancer for example). But these seem to be both safe and effective.

There really shouldn’t be a stigma associated with taking drugs like these for the rest of your life.

> patients who lose weight this way still needs this drug to keep it off.

Purely anecdotal N=1 but I was also 285 at one point in my life and went through an intensive weight loss program through my work and lost about 60 lbs in 3 months. That was about 15 years ago. Since then I've done several 3 day fasts and many weeks of One Meal A Day. I think that program showed me experientially what its like to go without as much food as I thought I needed.. so even when the program ended I had a totally different concept of food. Maybe this drug can do something similar. I think so much of overeating for a lot of people is just purely habitual or a misconception that 'my body needs food every 3 hours' when really it doesn't at all, that's just how you've currently conditioned it.

I have issues with my appetite. I eat a lot. So my fix was to exercise a lot. Which worked out fine. But now my hip has a pretty severe issue causing me to go from ~1,500+ calories per day burn to about half.

Add to that the fact that I sleep worse due to pain...

So my appetite is even worse, as I eat to compensate the lack of energy because of my bad sleep.

I want these meds, if only until I've had my surgery and have completely recovered.

And after that? We'll see..

Food abuse is instilled during childhood, it's incredibly hard to change. For alcohol abuse we accept that abstaining is the right thing to do. Can't do that with food, so we need some help.

If these meds work with minimal side effects, and people are genuinely having a benefit, why not?

>Should we be concerned about needing drugs to treat obesity?

This comment of yours made me think of this comment from another article about another obesity drug I read recently:

"The history of medicine includes the following story many times: there’s some condition that doctors recommend lifestyle changes for. Then an exciting new medication comes out that treats the condition effectively. Over a generation or so, doctors go from demanding the lifestyle change, to gesturing at the lifestyle change before prescribing the medication, to mostly just prescribing the medication. We saw this with cholesterol and statins, with hypertension and ACE inhibitors, with depression and SSRIs. You can form your own opinion on whether this is good or bad, but we’re probably in the very beginning of this process with obesity. Opinions will be all over the map for a while before the inevitable pharma company victory makes everyone agree that semaglutide is first-line therapy."

https://astralcodexten.substack.com/p/semaglutidonomics

I think your concerns are appropriate, but if there are people for whom drug-free practices are too difficult and not working, it might be a good alternative. It's probably better than bariatric surgery.

It's also not necessarily either-or: maybe lower doses might be enough to get someone over a hump or something with exercise and other lifestyle changes. Or some dosing protocol in tandem with other things might allow people to go off the drug eventually. Or maybe not. But it's early and who knows what research will show. Having another option that actually works and isn't harmful is better than not having that option.

honestly, what is wrong with you?

It causes thyroid tumors in rats, and thyroid tumors are among the most curable cancers.

On the flip side, people who are overweight are already on the road to T2 diabetes.

Obesity isn't just a cosmetic issue, it is a disease with very real health implications. If behavior modification doesn't work to lose weight, we shouldn't deny people effective treatment.

The supply chain will adjust to meet demand.

They are in the same class as semaglutide.

We know being obese has long term delayed consequences.

And they've been giving this drug to diabetics for a while and they seem to be fine and healthy.

Worse consequences that excess adipose tissue?

Sure, but being grossly overweight also has a tendency to “mess with insulin production”. That’s how type 2 diabetes works: your musculoskeletal cells become resistant to insulin and your pancreas produces more and more until it can’t keep up.

> No way messing with insulin production doesn't have long-term delayed consequences.

Not an expert, but this sounds most likely true.

Empirically, yes. Very few people who attempt to lose a substantial amount of weight via diet and exercise are able to lose the weight and keep it off over the long term. The latter part is the problem for most people.

Clearly it is in the US. I think it's a generational lack of understanding and poor habits. From my perspective each generation of an obese family seems to get bigger and bigger, and pass on those non-existent or bad habits to their kids. If your parents aren't modeling exercise and good behaviors the only avenue you have to learn from is school and that's easy to get left behind.

On top of that you're marketed with the shittiest food all day, your school probably serves food where only things like pizza and burgers are palatable.

It's all really a shame because exercise and eating well clear your mind and make you feel better. Even if you're a healthy weight eating shitty and sitting all day does things to your mental health.

Abstinence-only education always works!

I mean what percentage of the US is overweight these days, the number is scary high and it has a massive impact in productivity and Healthcare costs.

You misunderstand how weight loss works; it's controlled by the HPA axis and various related brain/gut/pancreas/liver/fat cell interconnects, not the neocortex. "Stop eating" is an input from the neocortex. It has very, very little impact on food drive. "Satiation/Nausia" is an input from primary metabolic regulatory systems.

People that are 'only a little bit overweight' are usually in that state because they can't control their eating via the neocortex. You can't simply say "eat a little better"; you have to modify food drive. The signaling pathway this drug targets is the one that feed into food drive.

Eating better and working out is hard. If the medication can get you a similar outcome with minimal side effects, that seems like a prudent protocol to prescribe.

If it’s determined to be safe (statistically), why not? Might only be necessary until we can inexpensively synthesize miR-1: https://news.ycombinator.com/item?id=34196488

If your BMI is over 35 (around 1 in 6 adults IIRC) it can make it hard to exercise. A little push in the right direction may be indicated.

The number of overweight people and diabetics far exceeds the number of celebrities out there. I think it's just demand driven by media exposure that is the issue

You can get these wholesale from China from "reputable" gray-market wholesalers who get the chemicals made at contract manufacturing facilities. Independent purity tests via HPLC are available for <$100 if you don't fully trust your supply chain. Semaglutide is very, very cheap in the gray market. It's somewhat less effective than Tirzepatide and has slightly more side effects if you ramp up the dosage too quickly.

If an annual amount is purchased on the gray market, this brings the monthly cost down to:

- Tirzepatide: $60/month

- Semaglutide: $10/month

- Liraglutide: $87/month

Note that in the USA, it is legal to import certain amounts of FDA-approved drugs if you have a prescription for them. However, just because something is the exact same chemical as an FDA-approved drug does not make it an FDA-approved drug. It must be manufactured in an FDA certified facility and be the same brand/manufacturer/packaging/labeling/etc as the approved drug.

e.g. importing generic Sildenafil/Viagra is legal if you can find the Teva(tm) brand generic sildenafil in, say, Mexico or Canada for a better price. But it must be the pills manufactured by Teva in the appropriate facility with NDC #0093-5342-56[0]. If you import generic sildenafil "Cenforce" from the (very legitimate but not FDA-approved) Indian pharmaceutical manufacturer "Centurion Laboratories"...

...that would still be potentially criminal smuggling. Even if the pills you import show via laboratory test that they precisely match your medical prescription, they are not "FDA approved" and therefore not legal to import.

A lot of people do though!

0: https://ndclist.com/ndc/0093-5342/package/0093-5342-56

Unfortunately it's really expensive to research and produce drugs and somebody's gotta pay for it. The rest of world isn't willing to so it looks like rich people's insurance is the one that will foot the bill which means lower income people have to wait.

It sucks and it's a inefficient way to fund research but it's better than the alternative where no one funds this research and we (both rich and poor) never get the drug.

Lower income people of 2036 and beyond will have a magical medicine for probably 30 bucks a month.

It's covered by insurance and the manufacturer has a $25/month program.

Running shoes cost about $50-$100 for a decent pair and last for many months

Sadly it seems that these drugs will be used for vanity without much regard for their safety.

All right, this is a single Data point, and of course is anecdotal evidence… if you’re into taking health advice off the Internet rather than from your doctor… well you probably will end up disappointed.

OK disclaimers aside now: when I switched to clipless petals on my mountain bike, I dropped 12 lbs over the course of the summer. SPD clipless work the hell out of your calves when they are placed under the ball of your foot, especially in mountain biking applications because you spend so much time out of the saddle.

There is so many lurking variables here and nothing was normalized. I just thought that was an interesting connection.

Possibly related: Insulin resistance is impacted by muscle protein.

https://news.ycombinator.com/item?id=14667430

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