Episode 69: GLP-1 Medications, Muscle Loss, and Strength Training: What the Science Really Says

In this episode of the Pound of Cure Weight Loss Podcast, Dr. Matthew Weiner and registered dietitian Zoë dive deep into the latest research on GLP-1 medications and their evolving role in weight loss, muscle preservation, and even potential cancer treatment.

They break down what the newest studies actually show — including why so many headlines are misleading, and how to interpret scientific research through a more critical lens.

You’ll also learn why strength training is non-negotiable during GLP-1 therapy or bariatric weight loss, what to know about oral semaglutide vs. injectable versions, and how nutrition plays a key role in maintaining muscle mass while losing weight.

Whether you're a patient on Ozempic, Wegovy, Zepbound, or considering medication as part of your obesity treatment, this episode helps you make more informed, science-based decisions.

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Transcript

Zoë (00:04)
Welcome back to the Pond of Cure Weight Loss podcast. You know the drill. We are here with you for another In the News podcast episode where we have taken different studies and articles because we know there is no shortage of media coverage on these GLP-1 medications. So we've got a nice lineup of articles and studies to go through with you today. Dr. Weiner, how are you doing today?

Matthew Weiner, MD (00:34)
I'm doing pretty good. I'm doing pretty good, you know, at the end of the week. I'm ready for the weekend. ⁓ Go listen to some live music.

So yeah, the weekend is actually where I spend most of my time working on the app. I'm a total workaholic, Zoe, I'm sure you know that about me. And so I do a lot of work on the weekend on the app. So if you haven't downloaded yet, a lot of the features are free. So it's called Pound Acure. It's on

Zoë (00:42)
Fun! Who are you seeing?

Matthew Weiner, MD (01:00)
the iOS and the Google Play store. And there's a lot of free features. So please check it out. Let me know your thoughts. I'd love to hear if you find it useful.

and we'll be adding a lot more features and really enhancing the AI quite a bit in the next ⁓ six months to a year. So we'll keep you informed on the podcast.

Zoë (01:17)
Yeah, absolutely. All right, let's dig right into our first article, and this is from Medscape, and the title of the article is, GLP-1 less frequent dosing may maintain weight loss. Dr. Weiner, I'd love your thoughts.

Matthew Weiner, MD (01:31)
So

this is a little bit of a teaser and it's important why you have to read past the first headline. So people are gonna be like, well, this is great. We can just, you know, space out our dosing and then we'll still maintain the weight. Now, first of all, that might be true. That might be a strategy. And we might be able to lower the dose. We might be able to stretch out the dosing interval. I think there's some options there for sure. But this study doesn't give us any information about that. This study had a total number of

of two people.

which is the minimum number of people you need in order for it to be a study. If it's just one person, it's a case report. If it's two people, it's a study, but it's not a very powerful study. And so they did show that people were able to maintain their weight, two patients were able to maintain their weight loss. And that is about as academic as me telling you, hey, I talked to two patients today and they were able to maintain their weight loss by switching to every other week dosing. ⁓ It is literally about as, or you talking to two friends.

is

that accurate. And so I think it's important when you look at this that you don't accept everything that has a scientific study behind it as accurate and true. Probably 90 % of scientific studies are either wrong or crap. And people publish studies in order to advance their career, gain notoriety. In general, a lot of studies are

published for the personal gain of the author, not necessarily the benefit of you, the patient. So I think that's an important thing to keep in mind. But it is an interesting question and it's one certainly that we'll be sorting through, but we're going to need more than two people to figure this one out.

Zoë (03:15)
Yeah, that's a really good thing to keep in mind, especially with not just articles and studies, but you know, even more so social media and just all these catchy, you know, hand grabbing titles or eye catching click baity titles. And we got to definitely look deeper. So that's a thing to remember.

Matthew Weiner, MD (03:23)
Bye.

Right.

Zoë (03:33)
next article comes to us from Reuters and the title of the article

weight loss drug helps patients on Wigovie preserve muscle.

Matthew Weiner, MD (03:45)
Yes, so this is a, this is, and this is a lot of people are thinking like, this is the next thing. And we see this, you know, with combination blood pressure pills where they have a little bit of diuretic and then lysinepril and they kind of put it together because people don't like to take two pills. They'd rather take one. You take one pill with two ingredients. You say to yourself, I'm only taking one pill. ⁓ But you're really taking two. And so.

They showed that by combining Wegovi or semaglutide with Trevogrumab, Trevogrumab and yeah, you know, in medical school they don't give you a pronunciation degree and Garectosmob. Where did they come up with these names? It's an antibody, but they...

Zoë (04:30)
don't know.

Matthew Weiner, MD (04:34)
Okay, let me just change it. They combined Wegovi or semaglutide with two drugs with very difficult to say names and they found that they preserved more muscle mass. So I'm assuming they did the impedance measurements. Zoe, how would you measure, how would you set that up if you were designing the study? How would you measure body mass and muscle loss?

Zoë (04:56)
Yes, absolutely. you can even just get the scales, like smart scales that give you the body fat measurement, that give you the...

the muscle mass and body water and different metrics like that, there's going to be a margin of error. It's not going to be super duper accurate, but at least it'll be consistent and that'll be something to track over time. And that's something that patients can use for their own data. I would hope that in a large study that they would be using something like a DEXA scan because it is so much more accurate where they can really get that good data around your body composition.

Matthew Weiner, MD (05:33)
Yeah, yeah, no, Dexascan is really the gold standard there for sure. So they showed that ⁓ you lost a little bit more weight, 11.3 % versus 10.4%, but you lost less lean muscle. ⁓ There was one really interesting caveat, which is 28 % of the patients stopped the treatment due to side effects. ⁓ That's a lot. First of all, if 28 %...

stopped it from side effects, that means probably at least another 28 % had the side effects but endured. We've seen this, I'm sure you've seen this, you know, where patients are like, yeah, I'm losing weight, but ⁓ it's rough. And that's not our strategy. That's not how you want to do it. You need to be comfortable. This is a long term drug. And so my first concern about this is, you know, do these other medications really cause a lot of side effects? The second is, you know, the chemistry starts to get really wicked.

as you move, as you add more and more of these medications. And I think the potential for harm goes up. you know, most drugs that are out there don't actually end up making it to market because we find something wrong with them.

Zoë (06:45)
Mm.

Matthew Weiner, MD (06:45)
And so when you've got three

drugs in one treatment, gotta believe at least one of them is not gonna end up being any good. So I don't know that I would be looking at medications as a strategy for preserving muscle mass, particularly when we have access to someone like Zoe, is probably, I really, think if you're gonna look for someone who is an expert in strength training and also weight loss from GLP-1s or surgery,

It's pretty hard to find someone better than Zoe. So you're a certified strength trainer. You're also in wicked shape. So talk to us about what you can do as a patient who's on GLP-1s to preserve muscle mass.

Zoë (07:22)
Yes.

I mean, that was the first thing I thought of is like, why would we take a medication when we can do this through, you know, our the habits that I work with patients every single day on, right? Most people, even if they don't know it and say it like we want to be preserving muscle. I would like to say muscle is this precious, valuable tissue. But it's it's like important that we put measures in place to preserve it, because otherwise

Matthew Weiner, MD (07:34)
Thank you.

Zoë (07:57)
your body will try to get rid of it ⁓ if it's not being supported, right? Because it is expensive to maintain. So there are two components for preserving muscle mass, especially when you are experiencing a rapid weight loss, whether it's from your bariatric surgery or the GLP-1s. ⁓

You know, obviously we're talking about in that scope because of that being the tool, but this is also relevant even if you're not on one of those tools. So we need to make sure you have proper nutrition and we need to make sure your strength training. So we need to make sure you're getting enough protein in to give your muscles those amino acids, not just muscles, but all tissue in your body need amino acids, right? But here's the other important part is

strength training. It doesn't need to be in the gym like with all the gym bros. It can be at home. You can do body weight strength training. You can do resistance bands. You can have hand weights. You can do the machines. You can... There are so many forms of resistance or strength training. We need the amino acids and we need the stimulus on the muscles. Now that doesn't mean you have to be in the gym five days a week, but if we can do two days a week minimum of some strength training, that's something that I...

you know, unless there's something major going on that would be a limiting factor for a patient, I would like to see almost everybody incorporating strength training into their routine because weight loss is...

mostly driven by the nutrition changes, but weight maintenance and muscle preservation is driven through intentional exercise. So we need the strength training and then combined with the, you know, kind of cardiovascular, that's different. That's not for strength. That's not for muscle preservation, for example, but in terms of that.

bigger picture, right? So I do believe that everybody needs to be adding in that's safe for them, strength training, along with that adequate protein.

Matthew Weiner, MD (10:01)
Yeah, I think you said something that was really important, which is two days a week of strength training. There's a huge difference between two days a week and no days a week. And there's a huge difference between

one day a week and no days a week of strength training. So you don't need to hit the gym for two hours, four days a week in order to preserve muscle and or build muscle. Just twice a week makes a huge difference in your body and your muscle mass. And I think that's important because otherwise it seems like too much like who's got four, I don't have that time, but 30 minutes twice a week makes a huge difference.

Zoë (10:33)
Yeah.

And also, you know, muscle preservation and muscle building aside, the benefits of strength training for bone health and, you know, ⁓ mental health, cognitive health, like hormonal health, digestion, sleep, like, you know, exercise, yes, but specifically strength training for, you know, maybe aging women, postmenopausal women, a huge portion of the population that we see.

And arguably that's the biggest population that are maybe afraid of strength training or back away from it because of, you know, unfamiliarity or, you know, intimidation or whatever it is. But my encouragement to you if you that if you're like, yeah, I'm intimidated by strength training or I've never done it before, just start small and it will make a huge difference.

Matthew Weiner, MD (11:33)
I think I would go out as far as and say that anybody taking a GLP-1 medication should be participating in strength training if they are at all physically capable of doing so. I mean, you got a walker and you're 74 years old. Okay, we'll give you a pass on that. But I'm sure Zoe would be like, but wait, no. Right? Yes, exactly. So even in that situation, yes, you're right. So let me take it back. True or false? Every GLP-1 patient should strength train in some form.

Zoë (11:52)
You can do seated exercises.

True, yeah.

Matthew Weiner, MD (12:03)
True.

Yeah. Yeah. So our take is if you want to preserve muscle on GLP-1s, eat right and strength train. I think looking at these muscle preserving meds, I think this is a pharma move. This is someone piggybacking. Yeah. This is someone piggybacking on GLP-1s and being like, GLP-1s are so popular. I'm going to make an adjunct. You know, and this is a money grab.

Zoë (12:12)
Yeah.

That is.

Matthew Weiner, MD (12:30)
not necessarily an advancement of science, in my opinion.

Zoë (12:34)
Yeah, and a money grab because think about what people talk about. Oh, I don't want to look too frail or I don't want to like look too skinny or I just want to be toned. Like I don't want to have like a whole bunch of loosey goosey skin or whatever. Like knowing that that's a pain point and preying on it by creating a money grab and like offering a kind of a quick fix where like marketing it as here, just take another pill.

Matthew Weiner, MD (12:45)
Right.

Zoë (13:04)
⁓ No, we want to we can do this. You can do this. Yes

Matthew Weiner, MD (13:08)
Right,

absolutely. All right, this next article I think is really exciting. This to me is the one that is the most exciting of all these articles. And I think, you know, this is a marker for what we're going to see that's going to change cancer care.

Zoë (13:24)
GLP-1

receptor agonists show PROMIS as adjunctive treatment for ovarian cancer.

Matthew Weiner, MD (13:31)
Yeah, so first of all, this was an observational study, not a randomized controlled trial.

So randomized control trial would be like, have two people, we have patients with ovarian cancer. We're going to select them out, control them, break them up into as equal groups as we can, and we're going to give some of them GLP-1s and others not. This was because so many people on GLP-1s, this was, hey, people who had ovarian cancer, let's pull out the patients who have been taking GLP-1s and let's look at what happened to them versus what happened to ⁓ people who didn't take it. So this is the classic correlation versus correlation.

causation. Just because two things are associated to each other does not mean that the first thing caused the second thing. That's really where a double-blinded randomized controlled trial comes in and that proves the causation. So this study shows a correlation.

between GLP-1 use and improved survival with ovarian cancer. Now the first thing you have to realize is that increased survival in a cancer study, it seems like all studies should show that. It's pretty rare actually.

the especially you're looking at two different chemotherapy regimens. I mean, they're looking at 1%, 2 % differences between these two regimens a lot of times and making clinical decisions and creating pathways based on very, very minor reductions in ⁓ cancer recurrence. We saw that in GLP-1,

patients taking GLP-1 receptor agonists that we saw, let me find this number. Yeah, so they had an overall survival during the follow-up compared with non-users. So again, correlation where the all-cause mortality of people not taking GLP-1s was 19.71%.

and the people taking GLP-1s, was 7.94%. So less than half the number of deaths in patients using GLP-1s. Now we know ovarian cancer is an obesity-related cancer. There's 13 of them out there. And we've seen with Wigovia and ZepBound that these medications result in cancer reduction risk. And so I'm not surprised, but I believe that we're going to see

GLP ones as an integral part of treatment for these cancers. The best part about it too is that it's a totally different pathway and in general a well tolerated medicine. So a lot of times they come up with two medicines but they work on the same pathway so you can't get both of them.

You know, you can only take one or the other, so it's a choice. So when you find a new treatment modality, a new pathway that doesn't take advantage of the other treatments, that's how, you know, that's how we essentially cured HIV, right? It was triple therapy. It wasn't one drug that fixed it. It was by adding multiple drugs, each one that takes a slice away. And so I think that's probably, you know, what we'll start to see with cancer. It's multimodal therapy. That's always been surgery, radiation, multiple different drugs.

But now we have this drug, it's a great drug. And I think it's gonna replace tamoxifen for breast cancer or potentially be used in conjunction with tamoxifen. And so this is really exciting because I think we're gonna start to see these medications very quickly come into the treatment protocols for cancer, for these obesity-sensitive cancers.

Zoë (17:11)
Do you think it's because it reduces overall inflammation in the body and that's the pathway or is it hard to say?

Matthew Weiner, MD (17:18)
So I was thinking about that, maybe that these, you know, and these meds are inflammatory reducers. Another possibility, I'm sure you're familiar with the calorie intake and longevity, that a low calorie diet increases your longevity. ⁓

And so there's ⁓ pretty good evidence that the less you eat, the longer you live because of the oxidative stress of food. ⁓ And so I'm wondering if it also has to do with just reduced food intake. ⁓ Interesting also what they showed, if you had metastatic cancer at the time of diagnosis, ⁓ then there was no survival advantage.

Now, one of the things when you have advanced cancer, one of the critical pieces of survival is nutrition. So the idea of giving a patient with metastatic cancer a medication that will decrease their food consumption, that's not going to sit well. And that also might show you that, you know, there was that, that while they, might've helped a little bit with the metastatic disease, the decreased food ⁓ intake also could have been harmful too. So I think that we might, you know, that, that remains to be seen.

could be either, Zoe. It's hard to say.

Zoë (18:33)
Well, and the other thing I was thinking about too is that a lot of women experience weight gain with breast cancer treatment. so having the GLP-1 on there could kind of, you know, obviously help with the mortality, but also that really painful side effect of the treatment as well.

Matthew Weiner, MD (18:39)
Yeah, big time.

Right, yeah,

Tamoxifen is a big weight gainer. So if you can take this medication instead.

and you lose some weight and also by reducing your obesity, you're reducing your risk of recurrence. So I mean, I think I would keep an eye out for this because we're gonna see these meds entering into the oncology space. ⁓ And again, this really gets to this idea that these meds are this miracle drug. I remember I was taught in medical school, there's no miracle drugs, they don't exist. You gotta find each drug, you have to find the indications in the treatment, but you know,

kind of being proven wrong here ⁓ because these drugs end up treating so many different parts of the body. I think this gets back to this idea that obesity is this disease that affects every part of your body. And so when you end up treating the obesity, you reduce the risk of every disease in every organ system. And so that's probably why it's the nature of the disease of obesity that explains why these

Zoë (19:31)
Yeah.

Matthew Weiner, MD (19:59)
are this kind of miracle drug.

Zoë (20:01)
Mm-hmm, really exciting stuff. All right, and we also are kind of ending on our last article, also very exciting potential revelation

Matthew Weiner, MD (20:04)
Yes.

Zoë (20:13)
Oral semaglutide by year's end, a GLP-1 weight loss pill.

Matthew Weiner, MD (20:18)
Yes, so first of all, not a new thing, Ribelsus has been out for a long time. When we first started our weight loss, our non-surgical weight loss practice, we actually used quite a bit of Ribelsus. We didn't know, I mean, we're like, yeah, pill better than a shot, why not? ⁓ you don't like shots? Okay, here's a pill. And we quickly realized two things about oral semaglutide. ⁓ Number one, not nearly the same degree of weight loss as what we saw with the injectable semaglutide.

And number two, a lot more side effects, a lot more nausea with these meds. And we were seeing it, you know, they had three, seven and 14 milligrams. Those were the starting doses of ribelsis. This is 25 milligrams. So this is almost twice the highest dose. So, so, you know, when I look at these studies, the first question I always have is because we know these are long term meds is what's the tolerance? And that's to me, such that's such a critical piece of this. If we're to get you lifelong weight loss,

you better light the med and tolerate it well. So there were 307 people in this and they split them up two to one. So that means about 200 people, 202 people went into, took the med and about a hundred and, know, 101 people, 102 people took the, were in the placebo group.

And they showed that only 167 people in an intervention group. So about 40 dropped out out of 200. So that's about 25 % dropped out. Yeah. And so my question is, you know, how did people do? They showed 13.6 % weight loss, which is getting close to Wegovi type weight loss. Still not at the terzepatide weight loss, but decent weight loss.

Zoë (21:47)
I don't know is maybe.

Matthew Weiner, MD (22:01)
They also showed another number I look for is non-responders. So ⁓ 80 % of people lost more than 5 % of their body weight, which stated another way is 20 % of people, it didn't really work. ⁓ And again, we see that not 20 % is higher than we see with with

trisapatite and semaglutide. Semaglutide is about 15 % and trisapatite, it's 15 % at the low doses, 10 % at the high doses. ⁓ And so we definitely see a little bit.

larger group of non-responders, a little bit less weight loss, and a little bit ⁓ more side effects. And so the thing I found, and Zoe, you know, I don't always hear the truth because people don't, you know, I don't know why, but they feel like they don't want to let me down. I feel like Zoe, you hear the truth. Do you hear people complain about taking a shot?

Zoë (22:58)
Not so much.

Matthew Weiner, MD (22:59)
Yeah, I think people want efficacy. Yeah, do people complain to you about side effects or lack of weight loss? Yeah, yeah, yeah, you hear about that all the time, right? That's what people care about, I think. We've been able to pretty much all but the greatest needle phobes to be able to get on board with the injection. Also, once a week, that's kind of nice, right?

Zoë (23:01)
The cons.

Yeah.

Yeah, absolutely.

Matthew Weiner, MD (23:29)
So I think that pharma companies are overstating the value of a pill. And I think that people care about side effects and efficacy.

Zoë (23:31)
Right? Yeah.

Yep, absolutely. And

they wouldn't have started if they weren't okay with giving themselves a shot.

Matthew Weiner, MD (23:51)
Yeah. Yeah.

Zoë (23:53)
So I remember, I don't remember if it was on the podcast or just a conversation we had had another time. Maybe quickly you could run through kind of how that mechanism of action is different when you inject the GLP-1 versus take it orally and how much more effective it is kind of spread throughout the body when you inject it versus having to digest it. So maybe if you have like a quick summary on that for our listeners.

Matthew Weiner, MD (24:20)
Yeah, so I mean, first of all, I think the important thing to note, Wigovie highest dose, 2.4 milligrams. This medicine, same drug, semaglutide, highest dose, 25 milligrams. So 10 times the dose. And what that has to, this all has to do with how our body breaks down medications. And so when you eat something,

it goes into, and a pill would count. That's really what we're doing. We're eating a pill. So it's going through what we call our enterohepatic circulation.

So what that means is that our body is designed that when you eat something, it first sends it up to the liver. And the liver is our detoxifying organ. And so it takes whatever you've eaten and it's designed to be able to store carbohydrates as glycogen, to process fats, and also to find toxins that could poison you and break them down into non-poisonous substances. And so when you take a pill, it goes through your liver.

However, when you take an injection, gets absorbed by the lymphatics and dumped right into your circulation and it doesn't go through your liver. And so because of that, it doesn't break down, which is why you can take a shot once a week, but you got to take the pill every day because our body is breaking down the drugs. We got to give it more. it because it breaks it down so frequently, it doesn't last as long. And so those are really the two components that

are an advantage of injection. And that's what we want. I they're talking about once a month, GLP-1 dosing. I think that would be super popular. To me, like that's the direction I think people will be interested in is, I take a shot on the first of the month and I lose all this weight. And especially if you can maintain a constant blood level, so there's not this fluctuation. ⁓ I think that's what people are gonna be excited about.

Zoë (26:17)
Yeah, absolutely. Lots of exciting stuff and I think we covered a lot of good ground. lot of exciting things, but also some like caution signs to know. Yeah.

Matthew Weiner, MD (26:26)
from crappy science too. We cover good

science, cover crappy science, we cover all science.

Zoë (26:32)
That's right. All right. Well, I hope you have a really great rest of your week if you're listening to us on Monday when we've dropped the podcast for you and Just a reminder search in your app store a pound of cure to download our app for

Use it out have it help you stay accountable on your weight loss journey and we are so excited to hear how you like it Dr. Weiner any closing thoughts

Matthew Weiner, MD (26:58)
No, think, you know, I would love to hear your feedback on this. So I think wherever through our social media channels or YouTube, you know, we made this app to serve you to help you sort through this. I've kind of always thought like, what do my patients need to know? What do they need access to? So they don't get into this spiral of self blame that we see so often. So they don't get on these kind of, you know, purchase these crappy things that they probably shouldn't be buying that are just essentially preying on their

desire for weight loss so that people get evidence-based ⁓ treatment advice and are able to make the best lifestyle decisions and really incorporate kind of this entire comprehensive metabolic approach. So that's my hope is that the app is able to deliver that. It's our first version. We got a lot of updates coming out, but I'd love to hear what's working, what's not working, what features you'd like. We do have a protein tracker coming out, so it will count your grams.

of protein in the next version that should be out probably not too far off from when this podcast drops. and that came from a patient who told me you know what I love it but I need protein I got to take it and I think also Zoe told me that too ⁓ but yeah we're listening. We're listening to your advice I promise so please let us know what's working what's not share it with a friend you know we hope this is helpful to you.

Zoë (28:14)
Yeah.

All right. Let us know how we can serve you. We look forward to the next episode and we'll talk to you soon.

Matthew Weiner, MD (28:30)
See you next time.