https://www.listennotes.com/e/f5409a0cbdc4451a89b34a0a966d41d0

So, Dr. Mott coming to you is an overweight patient. I'm interested in both the semaglutide and hormone replacement. And I'd like to get a general understanding of the semaglutide first, how it's going to work in my body, not having known that if I've got diabetes, I've heard that it helps diabetes, but will it work for me with the weight loss program without testing for that?

Yeah, great question. So semaglutide was first developed for the treatment of diabetes. So it does, it's called a GLP-1, glucagon-like peptide-1 agonist. It stimulates a naturally occurring peptide in our body that favors weight loss by decreasing appetite, by improving insulin activity. It actually works in the brain and the pancreas, which makes insulin, even in your GI tract. And it was designed for diabetes and it works for diabetes. It was first FDA approved for diabetes. But we noticed a side effect is those diabetics were losing far more weight than we'd expect normally with diabetic medications. So most diabetic medications do help with weight maintenance just by improving blood sugar. Metformin, some of the older SGLT2 drugs, they do improve weight typically, but not too drastically. Where this class of drugs did improve a class more drastically, somewhere between 15 and 20% of body weight was typically lost in the first year or so. It's actually a little lower than that in diabetics, but in people when they stay for weight loss. So then they started studying the same drugs, pretty much the same doses for people that did not have diabetes. So diabetes is a condition where your blood sugar is running a little bit too high or way too high, but the medication does not cause hypoglycemia. In other words, if you have diabetes, your blood sugar is too high, it'll bring it down, but it won't take normal blood sugar and suppress it. So it's safe to use in non-diabetics. And if you're non-diabetic and you're overweight, you know, you do your other lifestyle interventions are not working for you. This is somebody starts thinking about something like semaglutide or one of the other drugs of the same class. Now semaglutide was the first one FDA approved for weight loss. Now there's another one called tirzepatide. People like how it's called Zepval or Monjaro. So semaglutide is the one we hear about so much with Ozempic and Wegovy. Same drug, just different indications. And then the tirzepatide is Monjaro for diabetes and Zepbound for weight loss. Again, same medication. the reason they label them differently is because of insurance reimbursement and FDA approvals. So the FDA approval proves the drug for one thing. When they approve it for something else, they generally would call it something else. If it's not going to be covering the same disease, even though the drugs are identical. So the question you had was, should you know if you have diabetes? Absolutely. If you're a diabetic, that needs to be managed anyways. You still might be using the same exact drug, but then we're trying to get the end is not just weight loss. It's also management of blood sugar. In our practice, we're not treating diabetes. That's not our sweet spot. We treat more obesity or overweight. Patients, patients want to lose weight. But if you're a diabetic, your family doctor is really comfortable with prescribing these medications. And interestingly, it's way more likely to be covered by insurance if you're a diabetic than non-diabetic. So that might be another reason that then you talk to your family doctors and working with potentially other diabetes medications. Generally, these medications are synergistic with other diabetic medications as well, even with other weight loss medications as well. So they can be done in combination. So know if you have diabetes, not that's really critical. It's very simple tests to do. There's, there's something called glucose tolerance test or something called a hemoglobin A1C. These are both generally considered means to determine somebody as a diabetic or not. And keep it in mind, diabetes, it doesn't just happen. You grow sort of into it. So somebody's got a great blood sugar and they're really healthy, metabolically normal. They're normal. Then their blood sugar starts climbing up a little bit. Their metabolism changes a little bit. They start putting a little weight on. They're not diabetic yet, but they're pre-diabetic and we'll see changes on their blood work that suggests pre-diabetes but it's not yet diabetes. And if interventions don't occur, which principally is lifestyle intervention, but also potentially medications and diabetes results. And diabetes is a precursor to heart disease and certain cancers and even more Alzheimer's. So it's really critical to know if you have diabetes or not, and that's something your doctor would check.

You answered a couple questions in advance. So it will, the obesity will eventually, without intervening, most likely lead to diabetes.

So that's not entirely true. So we all have our genetics that give us risk for things. In my family, the men all died pretty young of heart attacks. and I've actually got the heart attack gene, about 25% of us has it has that. So doesn't mean I'm gonna have a heart attack, but it means I'm at more risk if I did not modify my lifestyle. My dad smoked or weight and take care of himself, got diabetes. And that's your epigenetics, how your body responds to your epigenetics. Some people are obese and never get diabetes for whatever reason genetically. They can tolerate that. They have more resilience, but in general, diabetes proceeds is preceded by weight gain. That's not always the case. Some people aren't that heavy, but that's generally the case. And, and overweight people have a much higher risk of developing diabetes, but it's not a sure thing. Now, if somebody isn't pre-diabetes based on lab works, the likelihood of them becoming diabetic is actually much, that's very predictable. That will happen if changes don't occur. And obesity itself, some people have, there's different areas where we might store fat. So, for example, somebody who has midsection obesity, the belly, the beer belly, the big gut, we'll call an apple figure, there are much more risk for diabetes than somebody would say thick thighs or.

Thick butt or thick legs. So there's even certain compartments that don't.

Risk diabetes as much as others. How soon would you see on the average with semaglutide or tirzepatide. So typically we see results starting after the first to third week. So it's pretty fast. Now in the clinical studies, we have a lot of data on these medications, which is very helpful. They really got FDA approved in a time the FDA had a very high scrutiny. And when studies can be done very effectively, then what we see is the most rapid weight loss occurs in the first 13 weeks. So you hear about people being on these medications forever. You don't need to be, but they were designed that way and probably for to some degree for corporate profits. because if they get you on this medicine forever. Let's talk about this. The maintenance dose at one year is 10 times higher than the original one month weight loss dose. 10 times higher because your body rapidly gets tolerant to it and it stops working as well. So what we see scientifically and in practice is people start losing weight fairly rapidly in that first three months, maybe four months, and then it really starts tapering off around 40 weeks or so. It pretty much stops. And in the clinical studies, they would take people that had lost weight and about 60 weeks, a little over a year. And they took a group of those people and some of them they said, well, stop the drug and stop your dieting and exercising. Typically in these studies, they want you to do some diet and exercise as well. And the other group, they said, you know, stay on the medication. And what they found was the people that stopped the drug and stopped exercise and stopped their restriction of calories, they gained weight back not super fast. And the amount of weight they gained back was based on how much they lost in the first place. So that people that had significant weight loss, such as 20% or more, had very little weight gain. And people that lost very little weight, pretty much gained it all back, maybe even then some, because they were going to go up anyways. From what we've seen in practice, is since the weight loss dose occurs mostly in that first 13 to 16 weeks, that's kind of the sweet spot to just go ahead and stop the drug then, and take what we call a drug holiday, where you discontinue it for 1 to 2 months. And during that 1 to 2 months of coming off the medicine, your tolerance pretty much goes away. You just actually start the drug over. at the much lower, much more tolerable dose, it sort of stair-step that weight down over time. We're finding that over a period of years, people get a better outcome doing it that way. They're not on nearly as much medication, far less expensive and far less side effects because most of the side effects occur from long-term use of these medications. There's also things you can do to increase the effectiveness of these GLP-1 drugs, at least theoretically. So one is adding a drug called metformin. metformin, which is another diabetic medication that increases the very receptor that the semaglutide or tirzepatide acts on. So metformin, there's something chemically almost identical that's a vitamin called berberine, B-E-R-B-I-N-E. That seems to do the same thing. There's also a probiotic that when taken orally called Akkermansia increases the GLP-1 in your gastrointestinal tract. So we see that these three things are things that people can do, not all together necessarily, to increase the effectiveness of their medication. And typically, we might not start that rate at the onset because the most common side effect of semaglutide or tirzepatide is an upset stomach. And same thing with metformin or bare brain. So we would start on semaglutide tolerating that well, we go into that holiday period where we stop the drug for a month or two, we'll start on metformin, increase the level, the target that the semaglutide is going after, and then resume the semaglutide again for another, you.

Know, 12 to 12, 12 to 16 weeks. Very informative, thank you. Now would you Consider somebody who wanted to do two of the therapies. So you have the obese patient that's interested in the semaglutide and also doing the hormone therapy hand in hand.

So they can be done together. Let's talk about this. So does HRT result in weight loss? Well, it's not linear. So we look at the bidirectional going both ways effect of low sex hormones. We're talking about testosterone, maybe estrogen and progesterone and obesity. so in men, you know, the title of the book I wrote is if your testosterone is low, you're going to get fat. That's kind of a catchy title. But men with low testosterone develop obesity and obesity leads to low testosterone. For women, what's the most common complaint in menopause? When they stop making sex hormones, weight gain. Everything about hot flashes and dry skin and everything, but it's weight gain is number one. There's a clear correlation between your hormones running out and weight gain, but there's other factors as well. As we age, our muscle mass might decrease a little bit. We might be a little less active. we might have worsened habits. So it's not purely hormonal, but there's a strong hormonal link. Getting back to men, men's health. If a man goes on testosterone, he can become thinner and heavier. So the paradox is a man who has low testosterone, his bones are a little thinner, his musculoskeletal system is a little bit lighter, and he's got some fat. But as he goes on testosterone replacement over time, say a year, his bone density rises, his musculoskeletal weight rises, and his fat mass or his lean mass so he may even stay the same weight roughly, take a 200 pound man, maybe he's 25% body fat. And at the end of the year, he could be 18% body fat, but still weigh 200 pounds because his bones and his muscles become more dense. Now long term, over a decade, yes, the weight, the fat definitely declines over time and the weight declines over time. In women, we see that with both testosterone and estrogen. So early studies in the 80s and 90s showed women on hormone replacement had less weight gain than women on nothing. So going on nothing for menopause leads to more weight gain than replacing with any type of estrogen. Using a topical or intradermal estrogen, something through the skin, leads to less weight gain than oral estrogen, which leads to less weight gain than taking nothing. However, women still typically gain weight after menopause. Even with hormone replacement therapy, they gain traditional hormone replacement there with some type of estrogen, but they'll gain less weight on estrogen. now, a large study done in or medium size done in Sweden and other studies as well has shown that testosterone, because that's actually your, your main hormone when you're, when you're younger, you have about 20 times more testosterone. A young woman has about 20 times more testosterone than estrogen. With testosterone replacement, they did a study on women in their 50s who were perimenopausal, and they put them on testosterone or placebo as a pellet, something that goes in the skin for six months. And the women that were on placebo continued to gain weight in their perimenopausal years, and the woman on testosterone had a slight weight loss. So it does favor weight loss. Getting back to this combination, if somebody is experiencing perimenopausal or andropausal weight gain, it is appropriate to treat both the underlying condition, the hormone deficiency, as well as the obesity with a GLP-1 in addition to lifestyle changes. And they can be started together. The GLP-1 drugs semaglutide and tirzepatide will have more of a rapid effect weight loss. And the sex hormone replacement is more about improving the underlying cause, which amongst other things is declined in sex hormones that leads to obesity, diabetes, other conditions.