Weight-loss drug found to shrink muscle in mice, human cells

>Losing weight without losing muscle mass is very hard.

I was with you up to here. In my experience it's easy to maintain a huge proportion of your lean tissue during a weight loss diet: Do some resistance training, get some protein, and don't lose weight too quickly.

There's no need to go to the extreme of a PSMF - which will still have you lose a bunch of muscle on account of being too big a deficit. If you can keep your calories reasonable while on a GLP1 agonist, there doesn't seem to be any reason you'll lose an exaggerated amount of muscle.

Intuitively, if you can lift a modest bench press (not novice, maybe beginner-intermediate) and you keep training and you consume a few fewer calories (not starve) why would you lose your strength.

For the average overweight person? I disagree. The average obese person does little to no resistance training, eats very little protein, and wants to lose weight fast so they're not paying for expensive GLP1 drugs for a long period of time.

You're asking folks to make three separate changes: start exercising, change their diet to add protein, and use GLP1s to reduce food amount. And reducing food amount already goes against adding protein, so whatever protein they were getting is going to get cut even further.

> In my experience it's easy

> Do some resistance training, get some protein

jeez, if people actually did that they wouldn't need the drug to begin with

Increasing exercise also goes against reducing food amount, because it makes you hungrier.

Because the body does not make it easy to keep the same muscle with less fat.

For most people, it just doesn't really matter, because their strength is so far below their peak capability it won't be hard to cut some weight while maintaining strength. The closer you get to the edge of capabilities, though, the more it will matter.

Bodybuilders I know seem to have a a very difficult time keeping their muscle gains while on a cut, I don’t know why someone who is not in a gym 5+ days a week and on an extremely optimized heavy protein diet measured down to the gram would expect otherwise.

Is it possible to go very slow and keep most of your lean muscle mass? Sure. Is it practical? I have my doubts.

Part of the effectiveness of these drugs - for me at least - is that results are rapid and that is a self-reinforcing feedback loop. Diets that had me losing 1lb/week were simply too boring and unmotivating for me to keep up beyond a few months. A few days of vacation “cheating” and you wipe out a month or more of incredibly difficult to achieve loss. Restricting yourself mentally in what you eat every day adds up to exhaustion over time.

Some folks can manage to lose very slowly while also adhering to a strict calorie deficit of a few hundred per day, while also being consistent with resistance training. I’d say the evidence shows that these folks are in the small minority.

I will say more evidence is needed for this drug class - especially where the harm reduction principle may be a bit iffy outside of obese folks. However it was life changing to me in the way it let me change my eating habits to very healthy protein and veggies as my primary calorie intake, as well as made going to the gym on a strict schedule motivating enough to actually come out at the end with a better bodyfat to lean muscle ratio than where I started.

These gains have continued since I hit my goal weight - and now I’m starting to become one of those folks who the BMI no longer applies to in a good way. I do wish there was a good way to test heart muscle mass like there is lean body mass with a DEXA scan as I’m curious if my increased regular workout heartrates translates into building back any heart muscle mass like it did other lean muscle. Certainly a concern to keep an eye out for!

I’m curious as you are if folks who are slow responders and live active lifestyles see the same muscle loss the hyper responders do. For reference I lost over 100lbs in just under 9mo. I absolutely lost considerable muscle mass, but have since put it back on and then some.

I mean when I needed to lose weight (15kg, 85kg -> 70kg) I started with calorie restriction, and as a result of that actually looked at what I was eating and realized I was incredibly low on protein, and then from that added some daily light exercise partly just to avoid getting bored and wanting food.

So this isn't really 3 separate unrelated changes. Also at least in my experience, people tend to regard high protein things as the "energy dense" part of a meal - the problem with a lot of carbohydrates is they're not very filling.

The biggest problem with exercise is it's an awful way to lose weight - you don't burn that many calories, it makes you hungrier, and then your body optimizes to burn even less calories as you do it.

I feel like a cut is a very specific type of weight loss where the person gets down to an unusually low body fat %. It’s to the point where each bit of fat loss is a significant portion of your body’s fat reserves. It seems different from when there is an abundance of easily accessible fat to burn.

It's notoriously hard to lose fat without also losing muscle. That's why bodybuilders bulk well past their target muscle mass before they cut for competition. I agree that you can do a lot to mitigate it through protein intake and resistance training, but you'll almost certainly still lose muscle when you're in caloric deficit, regardless.

It isn't hard to imagine that the last 10% of mass a bodybuilder has added was hard won and easily lost. That isn't representative of most people.

I'm not sure why this is so heavily downvoted. You raise some good points. I would add: The era of comical bulking is coming to an end. More and more scientific literature points to modest calorie surplus is the key to muscle gain (along with regular weight training).

I must disagree with your comment. Personally, I have witnessed so many people struggle for years with their weight. Being overweight and struggling to lose weight must be a 50 factor model: Multiple social, economic, and mental/physical health factors. These GLP1 drugs really are a game changer.

Furthermore, this effect is dependent on genetics. What is no problem for one guy in the comment thread could be very challenging for another.

Also, "just do proper resistance training" is a bit of a stretch when we're talking about what is practical to expect of the masses taking Ozempic.

So, yes and no.

If you're doing resistance training for the first time in your life or the first time in years, noob gains will outpace loss if you train hard and get adequate protein. This is the case for a lot of people on these GLP-1s, at least at the start.

But if you have a massive quantity to lose, as in a multi-year process, you won't be able to keep up the noob gains for the entirety, and then yeah, you're going to basically just be training hard and shoving protein down your face just to keep the muscle loss minimal.

Well, bulking and cutting cycles are pretty common for anyone beyond the beginniner stage when wanting to add muscle mass, even if they're more recreational or a powerlifter or whatever. It's just way more efficient to be in a large enough surplus to make hitting your macros easier and then diet after than it is to try and be super careful about it. The powerlifters aren't worried about getting down to that show ready <10%, they're just trying to not be fat, and they still lose some muscle.

If you are outside of your noob gains period and keep up your protein intake and resistance training you will minimize your muscle loss, but you'll still see some.

Bodybuilders will even take AAS that explicitly reduce catabolism of muscle mass like Anavar and still lose some muscle on cuts.

I'm someone that used to be fit and lifted regularly. Got busy, got lazy, got fat. Tried multiple times to get not-fat after getting fat, and found it to be too difficult for me, despite it not being something I struggled with for many years earlier on in adulthood.

Getting on tirzepatide made it trivially easy for me to get back to a better diet, start exercising, etc. I do have to force myself to have an extra protein shake to hit my macros, though.