[cthalupa]

What's the explanation for why GLP1 medications are negative things? There are a very minor subset of people that have some medically significant adverse reactions, but it is VERY small. We don't have any evidence to my knowledge of any long term risks with being on it.

[blackeyeblitzar]

GI issues are fairly common and sometimes linger after stopping too. Loss of muscle mass is also common.

[cthalupa]

The GI issues tend to be minor. Unpleasant, but not exactly any more debilitating than a lactose intolerant person deciding that they really really wanted that extra large milkshake. Some people have it worse - but those, to my understanding, very much are in the minority.

Tirzepatide also has significantly fewer GI issues.

Muscle mass loss happens in any sort of weight loss where you don't eat enough protein and get enough exercise. There's no current evidence that when you control for calorie deficit, diet macros, level of exercise, bmr, etc., that people lose more muscle mass on GLP1 agonists to my knowledge.

[jart]

Is there any evidence those things aren't just side effects of eating less food?

[oatmeal_croc]

This. You'll need studies to prove that semaglutide causes muscle mass -so you need to have a group that loses weight using semaglutide and another group that loses weight without it and compare the muscle loss. I'm willing to bet you'll see similar numbers. If you don't exercise, you will lose muscle mass when reducing weight - which is why trainers recommend resistance training and higher than usual protein while cutting.

[phil21]

GI issues are almost always minor. Folks are used to zero discomfort in their lives so the social media reporting of such is wildly overdone.

Tirzepatide is being investigated as a therapy for IBS. Within two weeks of being on the drug I was able to start living a life not scheduled around being near a restroom. This was suggested as a potential side effect by my doctor before taking it for weight loss, due to the GIP component in the drug which slows down your digestive track.

It could be I’m eating less. However I have went on crash diets before with absolutely no change to my constant lifetime GI issues, and have eaten extremely clean the past half decade due to a partner who cooks amazing healthy meals that would exceed most definitions of the term.

I’ve long since reached my goal weight and target body composition- but I plan on sticking to a low dose of Tirzepatide for the rest of my life since it gave me my life back. No more popping Imodium every few hours on vacation while simultaneously fasting. Just a normal life these days. I can enjoy a breakfast if I feel like it without it ruining the rest of my morning. Heck, I can even eat shitty greasy food at the state fair with only mild discomfort most folks would have from such poor choices.

Every study (still limited in number) I’ve read more or less refutes all the social media hysteria. There is a whole lot of smoke but no fires yet to be seen. They may still be coming.

The things that are not wholesale misinformation seem to be the requirement to cease use many weeks before going into surgery, potentially needing to be on it for your whole life, and the side effect it currently has on your finances. Nothing else seems to hold up under scientific scrutiny yet.

Perhaps I will regret this decision in 20 years, but I’m willing to take that risk to have some of the best quality of life years I’ve had yet.

[Alupis]

> We don't have any evidence to my knowledge of any long term risks with being on it.

Nobody has yet been on these drugs for an entire lifetime - which is what is being advocated in this thread.

[cthalupa]

Sure. But what's the proposed mechanism? For many - not all, obviously - medications, we have an understanding of potential long term risks. Animal studies catch some of them, others we know are potentially risky even without animal studies, e.g. drugs that increase angiogenesis have a risk of increasing tumor growth.

But no one has proposed mechanisms for GLP1 peptides.

Meanwhile, we know obesity is one of the largest long term risks to health in existence, and one of the most prevalent.

[throwup238]

> But no one has proposed mechanisms for GLP1 peptides.

I'm worried about long term malnutrition leading to significant loss of muscle mass, osteoporosis, and other deficiencies that eventually lead to infirmity and brings forward the immobility death spiral much earlier in late age through weak muscles and bones. Most of the long term studies on GLP-1 agonists that I've reviewed have been on diabetic patients who already had to carefully control their diets and we still don't know what decades of poor diet on Ozempic will do.

For very obese people the tradeoff is still pretty damn good though.

[cthalupa]

Probably more or less the same as to what happens with skinny people who have a garbage diet but just eat less or have significantly higher metabolisms.

It's not great.

The good news is it's quite commonly reported (and I can add my anecdotal experience to the chorus) that I don't crave the food that's worst for me in any real quantity anymore. Even if I'm busy and need to scroll through uber eats, I'm not using it as an excuse to get a delicious but large, fried, high in carbs, high in fat meal. It's way easier for me to say "yeah that tastes good, but I'll grab the grilled chicken wrap and brown rice."

I'm not sure on what causes this - we have some preliminary studies around GLP1 peptides, dopamine, addiction, etc., so it might be something there. But the sheer number of people you hear talking about it makes me believe we'll have some studies that do look into it in the future. It might not happen to everyone, and some people might still just choose to eat poorly even if it does, but in both situations people's longterm health depends on them listening to advice on how to eat better and exercise, and I think most people would rather be average weight and metabolically unhealthy than obese and metabolically unhealthy.

[DANmode]

As long as they don't use their brains to any high performing degree.

[__blockcipher__]

One obvious risk would be blunting of longer term GLP-1 receptor activation. Imagine type 2 diabetes but for ghrelin.

To use an analogy amphetamines have a honeymoon period, and it feels like a lot of people on these weight loss drugs haven’t been on them long enough to get past the honeymoon period and see what the effects are after 10, 20, etc years

[cthalupa]

It's possible. But, we've had another GLP-1 medication in use for about a decade and a half now - liraglutide. So far, we haven't seen evidence of that occurring.

I don't think anyone who is both informed and sane would suggest that it is impossible that there are negative long term impacts from taking the medication. Just that we have no current indication of them, and that being afraid about a "what if" without any concrete concerns when the alternative is the "continue being in one of the riskiest states possible for human health" is silly.

[CydeWeys]

People don't realize that Ozempic is already a third generation GLP drug, Mounjaro is a 4th, and the try generation drugs are already in wide scale clinical trials.

We do in fact know a lot about how these drugs affect people by now, and as you point out, we have well over a decade of data on them.

[rolisz]

Loss of muscle mass. Most folks on these drugs don't lose fat only, but a disproportionate amount of muscle too

[cthalupa]

That's the danger of any rapid weight loss where you don't exercise and ingest additional protein.

I knew about it from prior research, but my doctor made sure to mention it to me as well. He's also monitoring the speed of my weight loss to determine if I should go on ursodiol to prevent gallstones - another potential side effect of rapid weight loss.

But the same could happen on any sort of caloric deficit. The GLP1 drug isn't causing you to lose muscle through some reaction occurring inside your body - it's your body just doing what it does in a calorie deficit when you aren't overindexing on protein and working out.

[borski]

All significant weight loss includes some loss of muscle mass. Minimizing that is why every patient is advised and counseled to lift and work out, change their lifestyle and diet, and so on.

The pill alone isn’t magic. It just makes it possible to do the right things for people who found it impossible to do before.