Professor David Scott - Beyond the Scales: Preserving Muscle and Bone Health During Weight Loss

Is-- Do you think there's something that's mechanistically different when people are on these medications and they're losing that weight? Is there something through that process that's enhancing that lean mass loss, such as the bone and the muscle loss, or is it just a product of the massive weight reduction?

Yeah, it does seem to be primarily, as far as we can tell, just a, a, a, um, function of the, the magnitude of weight loss.

There's no real evidence in front of us that the drugs themselves have any direct catabolic effect on muscle or bone.

In fact, it's, it somewhat seems to be the case, at least in pre-clinical research, that, uh, these drugs could potentially have benefits for muscle and bone.

I don't think that's really being reflected in the clinical research so much, uh, to, to some extent.

Probably, again, because the magnitude of weight loss might just be so, uh, severe that, uh, any of those more modest, um, benefits that you might be getting in the muscle, uh, environment might not, uh, be so obvious- So, uh, it does seem to be related to the magnitude, but I think it's probably also worth thinking about the rate of loss.

There is some evidence that, uh, if we can keep weight loss at a fairly modest pace, so less than about 1% of total body weight per week, then our loss of lean mass probably falls in about the f- the 15% range in terms of how much it contributes to the total amount of weight loss.

When we seem to exceed that, and we get to about one to 1.5% of body weight per week or beyond, then we start to get in that range of, of maybe 25% of or more of the total weight loss being lean mass.

And so that's where we, I guess, start to say, "Okay, maybe this is an accelerated loss of lean mass that might not represent what we really want to achieve in terms of a healthy weight loss."

So is that percentage loss then probably one of the best clinical indicators, or are there other indicators where clinicians should suspect that maybe lean mass is taking place here as well?

We don't really have the evidence behind it to say very definitively, okay, when we lose weight at this pace, if we, if we're losing, uh, 15% of, of lean mass as a function of the total weight loss compared to 25%, are we actually seeing any real metabolic differences and functional outcome differences? So I think in that sense, it's, it's difficult to say definitively that, that we should be aiming for.

But I think there's probably a, a reasonable consensus among experts that that seems to be a desirable outcome and, and probably that if we, if we aim for that, um, we're, we're going to hopefully see better outcomes long-term for participants.

But I think the whole kind of issue with the GLP-1 spaces at the moment is we just don't have that long-term data to, to tell us those things, uh, really clearly.

So I guess a lot of what we're talking about when we're talking about this is kind of, uh, preventative, it's preemptive, that we're, we're thinking, "Look, we should just be doing these things, even though we don't know for certain that it, it necessarily is gonna have huge clinical, uh, ramifications." We know that losing a lot of muscle mass and bone is not healthy, uh, from all the other settings that we've seen it in.

So, you know, let's, let's, I guess, take the initiative to make sure that we're not, um, we're not causing that in, in this huge population of GLP-1 users.

Uh, I think that people are probably very familiar with obviously understanding that losing bone mass is not great.

Yeah.

And I think that a lot of clinicians would understand the importance behind maintaining muscle mass.

But could you just give us a bit of a quick summary around what is the consequences of losing that bone and muscle mass? Why is that so detrimental for long-term risk?

Yeah, I mean, it seems to be, um, obviously more the case in older adults.

I think older adults are the, uh, population who potentially fall below thresholds where, um, their muscle mass and bone mass, um, are at a level that, uh, it does prevent them from being able to live independently, uh, do all the activities of daily living that they need to be able to do to, to be independent.

Uh, and then of course, uh, to avoid f- uh, falls and obviously on the bone side particularly, a-avoid fractures from having, uh, low bone density and strength.

So, um, yeah, we-we've certainly seen that in the bariatric surgery setting, for example.

We now have kind of decades of data from, from bariatric surgery where we can actually, uh, identify that probably within about five years of, of bariatric surgery, those patients will have an increased risk of some types of fractures like, um, at the, the hip and spine relative to people who un- who don't undergo bariatric surgery.

Uh, and so we anticipate, given that GLP-1s now are, are achieving weight loss that are fairly similar into what we can achieve with bariatric surgery, uh, and that muscle and bone loss seems to be fairly proportional in terms of, of the total amount of weight loss, that the pattern will probably be quite the same.