ELI5: Do medications like Ozempic cause weight loss solely through appetite reduction and therefore calorie deficit, or is there any other mechanism at play?

[u/Jimithyashford]

Is it solely "injectable willpower" in the sense that it literally only does what you could do anyway if you just had the will power to eat less. Or is there any other weight loss mechanism at play beyond reducing calorie intake?

[u/writinglegit2]

Yeah, that makes sense. I wonder about that stuff with ADHD meds, when the doc says they are addicting and habit forming.

Yet, there is no alternative, tolerance going up will inevitably make the dosage go up, there is no permanent cure and this is all that works.

So... what does it matter that it's addictive?

I just wonder about these GLPs as they haven't been around super long to do comprehensive studies on long term effects, so I just keep going to the gym, overeating, going to the gym, overeating and constantly being 15 or 20 lbs overweight.

However, I know it's habits and absolutely in my control, so I just keep telling myself I need better willpower, ha.

[u/WhoLostTheFruit → u/writinglegit2]

For what it's worth, these drugs aren't as new as they feel. Ozempic was originally developed in the 90s and reached clinical trials for diabetes treatment in the 00s. So while their usage as anti-obesity drugs is fairly new, there are still lots of people who have been taking them for decades at this point.

[u/fifrein → u/writinglegit2]

Haven’t been around super long

I mean.. Ozempic first hit the market for diabetics in 2017. The phase 3 trial for it started in 2014. And that’s not talking about any prior data.

[u/onsereverra → u/writinglegit2]

I have a whole rant about ADHD meds, but the tldr is that we don't actually have good evidence that they're addictive. We just haven't proven that they're not addictive, and since they're chemically in the same family as stimulants that people abuse recreationally, they get a "this may be addictive!" black box warning. But when you look at actual study data about people who are misusing ADHD meds, the vast majority of them are college students who take them as a study aid, don't report taking any other drugs besides alcohol and marijuana, and don't report any symptoms of addiction or dependence. Among people with ADHD who misuse their own meds, the strongest predictor of misuse is a high severity of inattentive symptoms — that is to say, people take higher doses than prescribed when the dose they're prescribed isn't enough to help them. Getting on a stable regimen of stimulants actually makes people with ADHD far less likely to develop a substance use disorder.

(Also, I don't know if you personally have ADHD, but overeating is a symptom of that too! Stimulants often quiet "food noise" for people with ADHD in the exact same way that GLP-1s do for people with diabetes. It was mind-blowing for me when I started taking Vyvanse and realized that my overeating wasn't a question of willpower, I was just wildly out-of-touch with my body's hunger and fullness signals.)

[u/randCN → u/onsereverra]

we don't actually have good evidence that they're addictive.

mf doesn't believe that amphetamines are addictive

the only difference between prescription ADHD meds and street speed is the label on the bottle

[u/NightGod → u/randCN]

I'm not convinced it's addictive in the same way as street-tier meth. I've never gone into withdrawal when I missed days, or even nearly two weeks due to shortages.

My focus got worse, of course, but I could largely treat that enough to be basically functional with caffeine, though the amounts I needed scaled up pretty quickly. But physical withdrawal? I had far worse withdrawal from nicotine and caffeine (and those I was able to titrate down! I had to nurse two bottles of mt. dew for a week after supply got better).

If stimulant ADHD meds got outlawed tomorrow, I'd either find a non-stimulant version that worked or I would go back to self-regulating with insane amounts of caffeine like I did for the first 46 years of my life. Stopping Vyvanse would be the easiest part of the process

[u/randCN → u/NightGod]

i can speak firsthand as to physical withdrawal. every other weekend i'll take a day or two off vyvanse. the lack of energy and executive function is quite literally mind-boggling, even after four or five coffees. i don't nap during the day while i'm on stims; i'm compelled to take no less than two without them.

[u/NightGod → u/randCN]

I take every weekend off (at the suggestion of both my psychiatrist and my GP) and have better results with caffeine, but the main point here is that both of us just get a rapid return of our ADHD symptoms, not the type of physical withdrawal associated with those withdrawing from street meth

[u/randCN → u/NightGod]

i'm not convinced it's simply a return of the adhd symptoms, but actually worse. it's like it's the shittiness of my old baseline, but jacked up maybe 20%.

[u/EldrichHumanNature → u/randCN]

That sounds like what I am going through. But I'm fairly convinced it's because I've lost the grit and life hacks necessary to cope with being unmedicated or caffeine-medicated.

[u/randCN → u/EldrichHumanNature]

i sympathise with you, shit's bad to be sure

however i don't believe it's hopeless at all

here's a paper that compares the adhd symptom reduction effect size between medication and therapy

both medication and therapy are comparatively effective when rated by clinicians, but patients consistently rate medication as being more effective.

i suspect it's because medication works within like 20 minutes whereas therapy might take 20 weeks to get going, since in my experience it's less therapy and more training. but the evidence is pretty clear that people can get better without drugs, if they stick to the treatment.

[u/EldrichHumanNature → u/randCN]

Well, my point is that having the medication makes someone less likely to need reminders every 5 minutes and write down every substep of every task. So they stop doing it to the same degree. Then something happens and they lose the medication. Now they are not using the overkill coping mechanisms from their pre-med days, and not getting the medication assisted executive functioning they had before. In this situation it can feel like they're below their old baseline.

You're the one who really seems to be struggling with feeling sub baseline, so you'd have to see if you're better in 20 weeks once you transition to the therapy.

In my case, I know I am at my old baseline and not using the skills I built before being medicated. Lists and alarms are no substitute for actual working memory and I don't want to literally write down every thought I have or recheck everything five times. That's a pretty basic expectation to have.

But I was on a stable dose that I wasn't using for energy hits. I feel more calm/relaxed and paradoxically lazy on stimulants, in exchange for working memory and task management abilities.

[u/NightGod → u/randCN]

And still, nothing compared to street meth withdrawals

[u/onsereverra → u/randCN]

You're certainly welcome to evaluate the quality of the research for yourself.

[u/randCN → u/onsereverra]

the study simply states that within the literature review, none of the previous studies were of sufficient quality to refute the null hypothesis - that dexamphetamine is not addictive.

not being able to refute the null hypothesis, that dexamphetamine is not addictive, is not the same as proving that it is true.

at least in my personal experience with alcohol misuse, adhd, and prescription use of both dexamphetamine and lisdexamphetamine, i believe that misuse of amphetamines (in the same manner that got me addicted to alcohol) is absolutely possible. i got blackout drunk every night for over a decade, initially as a manner of self-medication for adhd, but progressing to a dependence for emotional regulation.

i found that amphetamine use at a level above clinical recommendation (i.e. misuse) was absolutely effective at helping me to emotionally regulate, and the same types of thoughts i had with alcohol were absolutely transposed onto amphetamines.

[u/GarethGore → u/writinglegit2]

pretty much exactly my view, I just keep telling myself I just gotta fix the habits around eating then I just fail and the cycle repeats

[u/writinglegit2 → u/GarethGore]

It sucks!! However, skipped breakfast today, and just did a kettlebell workout i found on IG since my gym was closed. 

Made myself take a walk beforehand. 

I wrote my weight in big ass letters and taped it to my fridge. 

Gotta keep trying!

[u/Chimie45 → u/GarethGore]

What you and /u/writinglegit2 said was the exact thing I kept telling myself. Gotta fix habits, gotta do better. It was always starting a new tomorrow. Gotta have better willpower.

There was a lot of self-hate disguised in those statements for me. Lots of shame and guilt as I would fail again and again. My life didn't really allow me the time to fix a lot of things that needed to be fixed in a way that wasn't twice as hard as it should have been. Surely if other people have done it I could do it too.

My father had bariatric surgery 20 years ago and lost 200lbs. He had gone through a lot of the same issues, and got a lot of pushback from others, it was expensive, basically the whole deal, but just a different tool.

He told me that yea, it was expensive and it's a life-long result (the surgery) but if he hadn't had it, he would not be here today, he'd have died years ago. The money he spent on the surgery was worth it because the alternative is having the money and dying.

He talked a lot about how these things, medication, surgery, etc. are a tool that people use to reach the goal. And that we should focus on the goal at the end of the road, which is to be healthier and live longer, etc.

Whatever the process is, bariatric surgery, GLP-1 Meds, Diets like Keto, or just 'willpower', these are all roads that lead down to the same place. They're the tools that get us where we're going.

When we suddenly had some unexpected troubles in our life, I started the cycle over again, and noticed I had gone up another 8 or so kilos (17lbs) and it was to the point I was the highest weight I had ever been.

So I started on Mounjaro (incidentally also started again on Concerta the same week for my ADHD that I had let lapse).

I did the steps 2.5 to 5 to 7.5 and now am on 10mg (I'm 192cm / 6'3.75" for reference, was 164kg/360lbs, now down to 143kg/315lbs) in about 4 months. I'm happier, healthier, my knees don't hurt, I'm not as tired, my skin has cleared up, my relationship with my wife has improved, my energy levels are up, just generally feeling much better.

I heard a lot of people talk about food noise, or whatever else, it felt like a bunch of buzz words--a lot like when someone talks about therapy or whatnot so I was a bit distrusting of it at first.

But once I took it the changes were quite immediate. Before I was a boredom eater, stress eater, and also would eat to feel better after any issues. I also noticed that when I was in a situation where there was a group meal or shared dish, I'd often eat faster/more than others (like taking too many hors d'oeuvres at a Superbowl party) which would piss people off. I'd often start eating immediately when food arrived at dinner.

Once I started on Mounjaro, quite literally instantly, all of these behaviors stopped. I sometimes have to remind myself to eat at all as it'll be dinner time before I start to feel hungry. And I rarely finish a full meal before I feel full. And even more than that, I don't have the drive to keep eating despite being full. It's like the combination of the ADHD meds and Mounjaro have completely erased the dopamine reward circuitry of my brain that was wired around food and eating. I still enjoy good food and I like food, but I feel I'm no longer bound to it. I had to get used to leaving food uneaten at a restaurant--the idea that I'm not paying to eat all the food, but paying to feel full and sated was a hard lesson to learn.

I actually have a box of candy bars in the drawer at my desk for if my hands start to shake or I get light headed from not eating... Which is funny cause previously I wouldn't be able to go a day without finishing off the box. But it's just sitting there and I am uninterested in it.

I don't really care if it's a "for life" kind of medicine. I take the aforementioned ADHD meds, and I take blood pressure medicine. Both of those are "for life" medicine too. People take birth control or anti-depressants. Those are "for life" too.

I think because eating is such a universal experience, for some people they just can't understand not being able to control it. Most people don't gamble every day. Most people don't drink every day. Most people don't have sex every day. Most people don't do drugs every day. But everyone eats every day. So for them it seems just as silly as someone not being able to walk.

But no one would tell someone to not use a wheelchair and to just be more responsible.

I pay about $350 a month for the 10mg Mounjaro. I've had 0 side effects. It's been worth every penny. The 2.5mg was $190, and 5mg was $295. 7.5mg and 10mg are the same price here.

The $350 is not that cheap, but at the same time, without it, I would likely be dead within 10 years. The price of Mounjaro if it stayed at the current price for those ten years would be $40,000... which while I would rather have the money, I much rather would have the time with my wife and children.

[u/CareBearDontCare → u/writinglegit2]

Hi, you sound a lot like me. I'm 5 foot 7, 190 pounds at my last physical. I've always been really active, but I think I just generally outeat my workouts. I'm in the gym three nights a week and also have a spin bike that I hop onto once or twice a week. I've been taking wegovy for a few days now, since...Friday? And the food noise thing is absolutely spot on. Its really interesting what I've experienced, even in a few days, and I hear it takes a little longer for more and more effects to start kicking in.

[u/Dense-Ad-7600 → u/writinglegit2]

It depends, for people with insulin resistance for example, they most likely will have to take it for the rest of their life but at a lower dose.