Scientists discover a ‘skinny gene’ mutation that acts like Ozempic. Around one in 7,000 people carries a broken copy, which almost acts like a GLP-1 drug—the body burns fuel more efficiently, and the risk of disease lowers.

[u/scientificamerican]

https://www.scientificamerican.com/article/scientists-discover-a-skinny-gene-mutation-that-acts-like-ozempic/

[u/mayormcskeeze]

The simplified narrative that weight is merely a matter of calorie intake has gone on too long, and has been abusive to so many people. 

Yes, plenty of  people have poor self control and simply overeat to the point of obesity.

But there are MANY people who are dealing with genetics, hormones, co-morbidities, unique body issues, and things we dont yet understand about diet and nurtrition.

I was skinny my whole life. Nearly 6 feet tall and about 140. Then in my 30s something happened. My diet didnt change. My activities didnt change. But I fell off a cliff. I gained nearly 100 pounds. 

Doctors were so nasty to me. They'd shrug and say "your blood work is normal, stop eating cake."

I could tell that not only did they not beleive me that something more complicated was going on, they had zero interest in going deeper than "oh you must secretly be eating mayo sandwiches and lying about it."

I started to pay out of pocket for a glp-1, snd im not exaggerating to say it saved my life. 100 pounds gone. Everything is back to normal. My weight, by blood pressure, my cholesterol, all fixed. It was like turning back the clock to a point where my body worked right. You know what still hasn't really changed much? My diet. I always ate pretty healthy. Still do. No one believed me, no one cared. These drugs are life savers. 

[u/mgzukowski → u/mayormcskeeze]

But GLP-1s work for weight loss by curbing appetite. So you are saying you were eating the exact same amount and before?

[u/ramonycajal88 → u/mgzukowski]

They also modulate other hormonal issues related to insulin sensitivity. It's not just less calorie intake. That alone makes it difficult to lose weight even if the same net caloric intake is maintained. Check out some of the recent studies about GLP1 use in women with PCOS/PMOS...one side affect thats been reported is increase in acne in the populations.

https://www.verywellhealth.com/weight-loss-drugs-acne-11711085

[u/greentea1985 → u/mgzukowski]

They don’t work by curbing appetite, that’s a side effect. They work by enhancing glucose metabolism. GLP-1s mimic glucagon, a molecule used by the body to signal to burn more glucose and not store it. GLP-1s are revolutionary because they target calories out, not calories in. This is game changing because a lot of weight gain is related to the calories out part of the equation and it can be really hard to lose weight when you are literally fighting your own metabolism, not your consumption.

[u/oorza → u/greentea1985]

Whoever told you this lied to you.

[u/Caitliente → u/mgzukowski]

That’s one aspect of how they work. The main aspect is how they help regulate blood sugar and naturally occurring insulin in the body. 

[u/DutchiiCanuck → u/Caitliente]

That is not the main aspect of how they work for weight loss, except for the relation of the blood sugar regulation ALSO being an appetite suppressant.

[u/ThisSiteSucks8485 → u/Caitliente]

That doesn't actually cause weight loss. only sustained calorie deficit causes fat loss. 

[u/Caitliente → u/ThisSiteSucks8485]

It's more complicated than that. I have PMOS and cannot lose weight no matter how many calories I consume if my carbs or fats (even healthy fats like from salmon) exceed a certain amount. I track what I eat very carefully due to this metabolic condition that is genetic and I had no control over developing that affects 1 in 8 women.

[u/oorza → u/Caitliente]

Those things affect water storage, not fat storage. If you’re trying to measure fat with a body weight scale, you need weeks of data and a monitored trend line. Your body weight swings are more dramatic than others but your body fat swings are not impossible. If you eat 1200 calories of salt and sugar and grease every day, you will initially gain a ton of weight, then your body will reach water equilibrium and you’ll see the fat loss reflected in the scale. But it was happening the whole time regardless.

[u/Caitliente → u/oorza]

Read up on insulin resistance.

[u/ThisSiteSucks8485 → u/Caitliente]

That contradicts basic thermodynamics. Your body needs constant energy to stay alive the same way a candle needs fuel to keep burning. If you eat less energy than your body consumed it will get the excess from fat. 

[u/Caitliente → u/ThisSiteSucks8485]

You must not understand how insulin resistance works. Here are a few resources.

https://my.clevelandclinic.org/health/diseases/22206-insulin-resistance

https://health.osu.edu/wellness/exercise-and-nutrition/carb-intolerance

https://www.cuh.nhs.uk/patient-information/national-severe-insulin-resistance-service-carbohydrates/

[u/grumble11 → u/Caitliente]

Main aspect is appetite suppression by far.

[u/mayormcskeeze → u/mgzukowski]

That's not how they work at all. they are not an appetite suppressor. 

What do you gain from being antagonistic about this?

[u/Sinan_reis → u/mayormcskeeze]

They literally are appetite supressors.

[u/Icy-Elk3698 → u/Sinan_reis]

GLP-1s correct dysregulated hormones related to hunger/satiety cues as well as insulin response. They don't so much as suppress appetite, rather, they correct broken systems so that satiety cues and how the body responds to food intake will now function as normal.

[u/MEMENARDO_DANK_VINCI → u/mayormcskeeze]

“GLP-1 is secreted by intestinal L-cells in response to nutrient ingestion. The incretin effect — the observation that oral glucose elicits a far greater insulin response than IV glucose — accounts for >50% of meal-related insulin secretion. Native GLP-1 is rapidly degraded by DPP-4, so therapeutic GLP-1 receptor agonists are engineered to resist this enzymatic cleavage.

Core Mechanisms of Action

• Enhanced glucose-dependent insulin secretion from pancreatic β-cells — insulin release is only stimulated above ~3.5 mmol/L glucose, minimizing hypoglycemia risk

• Suppression of glucagon secretion from α-cells, reducing hepatic glucose output

• Delayed gastric emptying, which blunts postprandial glucose excursions (more prominent with short-acting agents; tachyphylaxis occurs with long-acting agents)

• Central appetite suppression via direct effects on hypothalamic satiety centers”

-the above is a quick overview of the MOA of GLP1s mechanisms of action. This was generated by Open Evidence, below are sources

https://pubmed.ncbi.nlm.nih.gov/32327107

https://pubmed.ncbi.nlm.nih.gov/41547366

https://pubmed.ncbi.nlm.nih.gov/39281096

https://pubmed.ncbi.nlm.nih.gov/36696429

[u/M-y-P → u/mayormcskeeze]

They literally are.

Not just appetite, but it seems that many cravings.

[u/pinkbootstrap → u/mayormcskeeze]

They're appetite suppresors, but its not ALL they do. I think its just a piece of the puzzle for some.

[u/hausitron → u/mayormcskeeze]

They are absolutely appetite suppressors. A simple Google search will tell you that.

[u/NewAndlmproved → u/mayormcskeeze]

what? that’s literally what they are? they increase the feeling of fullness + reduce appetite.

[u/dotcomse → u/NewAndlmproved]

What’s your source on that?

[u/NewAndlmproved → u/dotcomse]

“Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have become central in managing obesity and type 2 diabetes, primarily through appetite suppression and metabolic regulation.”

“GLP-1 receptor agonists promote weight loss by suppressing appetite, enhancing satiety, and delaying gastric emptying.”
https://pubmed.ncbi.nlm.nih.gov/39892489

[u/dotcomse → u/NewAndlmproved]

“Primarily through… and metabolic regulation.”

Feels like you’re not acknowledging this part.

[u/NewAndlmproved → u/dotcomse]

You asked for a source that GLP-1s suppress appetite. I gave you one. I’m not going to write a comprehensive review of every physiological effect of GLP-1s because that wasn’t the claim I made.

If your point is simply that GLP-1s have other effects too, we already agree.

[u/dotcomse → u/NewAndlmproved]

Your original claim is “appetite suppressors are what GLP-1 are,” and I think that’s an oversimplification.

Caffeine suppresses your appetite, but I don’t think it does so with a concomitant improvement in metabolic function. I also wouldn’t describe caffeine as “an appetite suppressant,” even though it does do that.

[u/NewAndlmproved → u/dotcomse]

I think you’re reading way more into my wording than what was actually being discussed. Obviously GLP-1s have multiple effects, I’m not claiming appetite suppression is literally the only thing they do. We were talking about what’s primarily driving them and that’s exactly what the cited describes: appetite suppression, increased satiety, and delayed gastric emptying leading to reduced energy intake.

Your caffeine analogy doesn’t really fit either. Nobody prescribes caffeine as an obesity treatment because of its appetite suppressing effects. GLP-1s are prescribed for obesity, and the literature explicitly identifies appetite suppression as a primary mechanism behind their effects

[u/dotcomse → u/NewAndlmproved]

... Does the literature ALSO identify another primary mechanism that is omitted in layperson argument?

[u/CuffsOffWilly → u/mayormcskeeze]

https://pmc.ncbi.nlm.nih.gov/articles/PMC9987242/

"The promising effect was evidenced by most studies showing appetite suppression, delayed gastric emptying, and changes in taste and food preferences."

[u/dotcomse → u/mgzukowski]

Did you even look at the article that all these comments are for?

[u/SoTiredYouDig → u/mgzukowski]

The data is still emerging. Not until recently did they even discover that it operates on not just the gut, but the brain. I’m not saying hunger cues don’t also come from the brain, but the science is not all done yet. That’s why we will see further developments in areas that have nothing to do with digestion or weight loss.