Shrinking the Noise: A Real Conversation on GLP-1s

GLP-1 medications are everywhere, and for people who have fought their weight for decades, the results can feel like someone finally turned down the volume on cravings and “food noise.” I’m Krista Guidenti, and I’m equal parts fascinated and cautious. That mix matters, because therapies that change biology this fast rarely come without trade-offs, and I want us to be able to hold hope and scrutiny at the same time.

We start with the basics of GLP-1 (glucagon-like peptide-1) and why drugs like Ozempic, Wegovy, and Mounjaro can change appetite, satiety, and blood sugar control in a way that goes beyond willpower. Then we get honest about what people are reporting and what clinicians are watching: nausea, constipation, reflux, fatigue, and the more serious concerns that keep coming up in the conversation, including pancreatitis and gallbladder issues. We also dig into one of my biggest worries, muscle loss, and why preserving lean mass is non-negotiable for metabolism, strength, bone health, and healthy aging, especially for women in perimenopause and menopause.

Cancer questions come up a lot, so I walk through where those fears originated (early high-dose rodent studies and thyroid warnings), what human data generally suggests so far, and why “no clear signal” is not the same as decades of certainty. From there, we explore what happens when you stop GLP-1s, why weight regain may point to obesity as a chronic disease, and why people are experimenting with microdosing and intermittent dosing in search of a minimum effective dose. Finally, we look at what’s next, including retatrutide and the rise of even more powerful multi-pathway obesity drugs.

If you’re navigating GLP-1 weight loss, obesity medicine, and long-term metabolic health, listen, share this with a friend who’s curious, and leave a review so more people can find the show.

Transcript

Welcome To Serenity And Fire

Krista 0:11

Welcome to Serenity and Fire, the podcast where wellness meets crit. I'm your host, Krista Guidenti, founder of Panacea Luxury Spot Boutique. Join me as we dive into the intriguing world of biohacking, clean living, cutting-edge spa trends, and the hustle, grind, and grit of entrepreneurship. From my personal battles with weight management and fertility, and the 30-year journey to create and launch my dream business, to building a sanctuary for those who have been touched by cancer, I'm here to share real talk, inspire big dreams, and spark a passion for holistic living inside each and every one of you. So let's dive in. Welcome back to Serenity and Fire.

Why GLP-1s Spark Obsession And Doubt

Krista 0:50

So today I have a confession to make, and that is that I am absolutely fascinated with GLP1 medications. I'm also incredibly cautious about them too. I definitely understand why millions of people are taking them, and I understand why so many people love them. I mean, look at some of the results you're seeing in people that you know. I understand that some people feel that these medications have definitely changed their lives. And anecdotally, we're seeing that in people. I'm seeing it in friends and people that I know. And I also understand why some experts have concerns. But if you've struggled with weight your entire life, like I have, and you've lost weight and regained it, if you've counted calories, tracked macros, tried every single diet on the planet, watched other people sit around you and eat whatever they want while you gain weight simply by looking at a cookie. How do you ignore something that appears to work so profoundly? And how do you ignore something when everyone around you seems to be losing weight when they were always struggling with it their whole lives? And how do you ignore something that people are describing as life-changing? I understand the appeal. I really, really, truly do because I've felt it too. And I've been so super conflicted with this topic. And at the same time, I have so, so many questions. Things like, are these medications safe over the long term? Are we losing fat or are we actually also losing muscle? And what happens to your digestive system? I've heard some crazy stories and actually have people who are very close to me who have had some major medical incidences. And I also wonder, do people have to stay on these medications for forever? Or can they take them in small doses, go on and off them? What's going to happen once they stop taking the medications? Are they then gonna gain back all of that weight again? And are there things that we don't know about these medications that we're gonna later discover 10, 15, 20 years down the road? I also wonder, do people actually even enjoy food anymore? I mean, one of I think the pure joys in life is having meals and enjoying food and trying different cuisines and it's what we center a lot of our activities and entertainment around. So I wonder about that. And then I wonder, are we treating obesity or are we simply suppressing appetite? So are these medications too much of a good thing? And perhaps the biggest question of all is can something feel miraculous while also deserving careful scrutiny? And I think the answer to that is yes. So as promised, today we're talking about GLP ones, Ozempic, Wagovi, Manjaro, and a newer peptide that you maybe haven't heard about. And these medications all seem to have changed the obesity conversation almost overnight. But before we go any further, I want to say something right up front. This is not an anti-GLP one episode, and it's also not a pro-GLP one episode either, because I don't think the answer is quite that simple. I think these medications are incredibly promising, but I also think that they're incredibly powerful and that they deserve thoughtful questions and thoughtful conversations because powerful therapies almost always come with trade-offs. And I think that we're still learning what many of those trade-offs

GLP-1 Basics And Why They Work

Krista 4:09

might be. So let's go back to the basics and quickly revisit what GLP1 stands for. It's glucagon-like peptide one. It's a naturally occurring peptide hormone that your body already naturally makes, primarily in the intestines after you eat. And its job is to help regulate blood sugar, insulin release, glucagon, stomach emptying, satiety, and appetite. In very simple terms, GLP1 is one of the body's natural signals that say, hey, we've eaten, slow down, we're satisfied. And in case you missed my last episode, scientists originally became interested in GLP1s because of diabetes. Their original goal was to see if they could simply improve blood sugar control. Weight loss really wasn't their original objective, at least not initially. And then something really interesting happened. Patients started losing weight. And for some patients, it was tons of weight. And they were saying things like, I don't think about food all day anymore, I don't obsess over food anymore, my cravings are different, I finally feel full, I finally feel in control. It wasn't a conversation of them just trying harder and having more discipline. Something much bigger was definitely happening here. And these medications appeared to be influencing things like hunger signals, satiety signals, reward pathways, cravings, and food noise. And suddenly the obesity conversation started changing dramatically. GLP1s, again, didn't become popular because they're weight loss drugs, they became popular because they appear to change the biology that drives obesity.

The Emotional Reality Of Obesity

Krista 5:45

But for many people, these medications genuinely felt and continue to feel miraculous. If you spent 20 years chasing and battling your weight and suddenly the food noise quiet down, the cravings decrease, the scale finally starts moving, that's super emotional. And that's hope and that's relief. And for many people, GLP ones don't feel like medications, they feel like freedom. So I don't think we should dismiss that because obesity isn't a simple cosmetic issue. It's associated with heart disease, diabetes, fatty liver disease, sleep apnea, joint degeneration, certain cancers, and diminished quality of life and so many other things. And for some people, getting the weight off may quite literally save their life. And if someone has tried everything else, I can completely understand why these medications feel incredibly appealing. And I think that's why this class of peptides is so difficult to ignore. Because if you've struggled with weight management your whole entire life, these drugs are emotionally difficult to reject. So I understand why people are tempted. I'm even tempted, and I think a lot of other people are too. Maybe, maybe that's the case for you because obesity is so frustrating and it can feel so super unfair. It can feel exhausting. You can do everything right, you can lose weight, but then you gain it back, and then you work harder, and then you gain it back even more. And then suddenly millions of people seem to be succeeding with these medications. So of course you're curious, and of course you're hopeful, and of course you're wondering, could this finally be the thing for me, the thing that can finally work and help me get this weight off? And I think that's a very human response. At the same time, the other side of me says, okay, what are we not seeing yet? Because history has taught us something, and that's that every powerful therapy does come with trade-offs. Sometimes we know what those trade-offs are immediately, and sometimes we don't discover them until years later. That doesn't necessarily make these medications dangerous, but I do think that it is something that we should remain curious about. Because right now, there are still so many things that we don't know about this class of drugs. So let's talk about some of those concerns

Side Effects And The Muscle Loss Fear

Krista 7:53

because they are definitely real. People are known to experience nausea, vomiting, constipation, diarrhea, reflux, bloating, abdominal discomfort. And I feel like that's kind of the case with pretty much every drug out there. I mean, listen to any commercial that you see on TV, but there's also concerns around pancreatitis, gallbladder disease, gastrointestinal motility, nutrient intake, long-term digestive changes. And then, of course, there's this other issue of muscle loss. And that has a lot of people really concerned. You hear about people talking about osempic face or osempic butt. And losing fat and muscle is not the same thing as just simply losing fat. Muscle really matters, especially as we continue to age. It influences metabolism, insulin sensitivity, bone health, healthy aging, resilience, strength, and independence later in life. And I want people losing fat. I definitely, absolutely do. I want to lose fat myself, but I don't want people sacrificing meaningful muscle mass in the process, especially women and especially as we age. And especially during perimenopause and menopause, because muscle becomes so incredibly important later in life. So the goal isn't to just simply lose weight, it's to improve your health overall. And those aren't always unfortunately the same

Cancer Concerns And What Data Says

Krista 9:12

thing. Now let's talk about the concerns around cancer markers with GLP1s. But before we talk about what we know today, I think it's important to understand where this concern came from in the first place, because it didn't come out of nowhere. It came from early animal studies. When researchers were developing some of these medications, they gave rodents very high doses of GLP1 receptor agonists over long periods of time. And in some of those studies, the rodents did develop tumors in specialized cells of the thyroid called C cells. More specifically, there were concerns about a rare type of thyroid cancer called medullary thyroid carcinoma or MTC. Because of these findings, GLP1 medications now carry an FDA-boxed warning advising against their use in people with a personal history of medullary thyroid carcinoma or multiple endocrineoplasia syndrome, type 2, or men 2. And understandably, those animal findings got people's attention. The original cancer concerns didn't come from people developing cancers on GLP1 medications. They came from rodent studies that raised questions that we need to investigate further. But here is why rodent data doesn't always translate to humans, and where this conversation becomes a little more nuanced. Rodents have a much higher density of GLP1 receptors on their thyroid C cells than humans do. In fact, human thyroid appears to express very few of these receptors, which means the biological response seen in rodents may not actually occur the same way it does in people. This is one of the reasons animal studies are incredibly useful for raising safety questions, but they don't automatically predict what will happen in humans. Animal studies are often the beginning of the conversation, not necessarily the end of it. Then there were also concerns about pancreatitis, pancreatic inflammation, and pancreatic cancer. Because GLP1 receptors are present in pancreatic tissue, researchers wanted to make sure that stimulating this pathway wouldn't inadvertently increase pancreatic risks. Again, these concerns prompted more research, and thankfully that's exactly what happened. Thus far, large human studies have generally not shown an increased overall cancer risk with GLP1 medications. In fact, some newer observational studies are beginning to explore whether these medications may actually be associated with lower rates of certain obesity-related cancers, lower cancer progression rates in some populations, and potentially improved outcomes in certain circumstances. Now, before everyone gets super excited, that's not proof. Those studies are largely observational, and observational studies can show associations, but they can't prove cause and effect. The absence of evidence of harm is not the same thing as proof of long-term safety. And early signals of benefit are not the same thing as proof of protection. And all of this is, of course, personally important to me because, as most of you know, panacea has a specialty focus in oncology therapeutics. So naturally, cancer is one of the things I think about literally all of the time. And here's where I sit with all of this personally. I don't know that the story is that GLP ones can necessarily cause cancer. And I also don't know if they can prevent cancer. At least we're not seeing that yet in the data. But I do think the story is that we're still writing the book because these medications are still relatively super new. And if history has taught us anything, it's that sometimes therapies do end up being even better than we expected, but sometimes we also discover trade-offs that we didn't anticipate. And sometimes both things can be true simultaneously. So perhaps the bigger question researchers are now asking is this could reducing obesity, insulin resistance, chronic inflammation, fatty liver disease, and metabolic dysfunction ultimately reduce the risk of certain cancers? I think it's definitely possible. Researchers are actively exploring that question right now, and I think it's an incredibly interesting area to watch. I think it's definitely possible, and researchers are actively exploring that question right now. And I think it's an incredibly interesting area to watch because with GLP1s, the cancer story may turn out to be far more complicated and maybe even more enlightening than anyone initially

Food Enjoyment Versus Appetite Suppression

Krista 13:17

expected. So let's move on to my other question about whether or not people actually enjoy food anymore. And I think this is a fascinating question because some people say I finally have peace around food. Others say I actually have to remind myself to eat, while others say nothing sounds good anymore. And those aren't necessarily the same experience. Food isn't simply calories. Food is, to me at least, pleasure, culture, connection, family, celebration, community. And I think it's reasonable to ask at what point does appetite regulation become appetite suppression? Is there a healthy balance? Could there be such a thing as too much satiety? I honestly don't know, but I do think that those questions are worth asking. And

Regain After Stopping And Chronic Care

Krista 14:02

maybe the biggest question of all is what happens when you stop taking these GLP ones? Because obesity appears to have powerful biological drivers. And if the medication changes those biological signals, then what happens when it goes away? The data suggests many people regain at least some of the weight back. So does that mean that the medication has failed? I don't necessarily think so, but it may simply mean that obesity does behave like a chronic disease, which is something that I think a lot of people don't want to admit, but that we're all starting to definitely recognize. And if obesity is a chronic disease, should we be surprised that some people need chronic treatment? At the same time, if someone hasn't addressed emotional eating, stress eating, sleep, nutrition, movement, muscle building, coping strategies, and behavioral habits, what happens when the medication is removed? In my mind, I think that they're most likely going to gain all of that weight back. So biology matters, but behaviors actually still matter too. So

Microdosing And Intermittent Dosing Questions

Krista 15:05

this takes us to another area that I feel like is getting a tremendous amount of attention right now, and it's something called microdosing and also intermittent dosing. And I really find this part of the conversation super fascinating because I think it highlights just how much we're still learning about this whole class of peptides. So, what is microdosing? In simple terms, it generally just means using smaller amounts of the medication, doses substantially lower than traditional protocols, or sometimes using the medication less frequently than standard dosing schedules. And here's something important. There actually isn't one universally accepted definition. This isn't like saying take exactly five milligrams. It's more of an emerging practice pattern than an established medical protocol. So what about intermittent dosing? It's kind of similar, and examples might include taking medication every other week instead of every week, or temporarily cycling off the medication, or using it during periods of increased hunger, or using it when weight gain begins reoccurring. Again, lots of experimentation, very little long-term evidence. And I think that's really important to say because I don't want people leaving this episode thinking, oh great, scientists have this figured out. They actually haven't, and we're still just learning a ton. So microdosing and intermittent dosing may ultimately become part of the GLP1 story, but right now we're still writing this chapter as well. So why are people even looking at microdosing or intermittent dosing? And I think the answer to that question is because people are starting to ask questions like, do I need maximum appetite suppression to experience meaningful benefits? They're also asking if more is always better. And what is the minimum effective dose? They're also looking at whether or not they can maintain benefits while minimizing side effects and if treatment can become more individualized. And I think all of those things are really smart questions and are the kinds of questions that medicine should be asking and is currently looking at. And when we look at side effects, I think that's another real reason why people are experimenting with lower doses because they are definitely real. People are experiencing nausea, vomiting, constipation, bloating, reflux, fatigue, food aversion. Some are having wildly serious medical complications. But for some people, the medications work so beautifully. And for others, it feels like too much. So naturally, people begin to start wondering could a smaller amount provide enough benefit while reducing some of the trade-offs? And again, I think that's a super reasonable question. And I also think this conversation becomes super fascinating when we start talking about food itself and that whole conversation around food enjoyment, because some people don't want food noise eliminated completely. They simply want it turned down from a 10 to a four. And I love that because I think millions of people understand exactly what that means. And then when we get into the muscle loss conversation, this is really where microdosing becomes super interesting. Because one of my biggest concerns is the muscle loss that people are experiencing with GLP ones. We've already talked about why muscle matters, it influences metabolism, insulin sensitivity, strength, resilience, healthy aging, bone health, independence later in life. And the concern becomes that if appetite suppression becomes so profound that someone isn't eating enough, isn't consuming enough adequate protein, isn't resistance training, and isn't refueling their body appropriately, then we may not simply be losing fat. We may be sacrificing that valuable lean body muscle mass. So naturally, people begin asking, could lower doses preserve some of these great benefits while also reducing some of these unwanted trade-offs? Could someone still improve appetite regulation, reduce food noise, improve metabolic health while also eating enough protein, preserving muscle, enjoying quality of life, and continuing to enjoy food? And I think all of those are super reasonable questions, but right now we just don't have definitive answers. So when we get into the obesity conversation and we start thinking about obesity as a chronic disease and the fact that it has powerful biological drivers, if these medications are changing those biological signals, we really do need to consider the fact that some people may definitely need long-term chronic therapy. And that shouldn't necessarily be a surprise to us because we don't look at someone with hypertension and say, well, your blood pressure is improved, so stop your medication. And we don't say to people who have high cholesterol, stop your medication because your cholesterol improved. Sometimes chronic diseases require chronic management. And perhaps obesity deserves to be viewed similarly. But here's the next question: Does chronic management automatically mean full dose forever? Maybe, maybe not. And that's exactly what researchers are trying to figure out. And if all of this sounds like it's moving incredibly fast, it's because it definitely is.

Retatrutide And The Next Wave

Krista 20:06

And while we're still trying to answer all of these questions about today's GLP1 medications, researchers are already developing the next generation. And one of the medications that's getting a tremendous amount of attention right now is called retitrutide. And it's super fascinating. I actually just recently learned about this from my really good friend in Canada. He knows someone who's been taking this, so of course I had to dive deep into this. And what's really interesting about it is that with today's GLP1 medications, which primarily target one major pathway, with retitrutide, it actually targets three. So it's focusing on GLP1, glucagon, and something called GIP, which stands for glucose-dependent insulinotropic polypeptide, which is quite a tongue twister. So try to say that three times fast. But like GLP1s, it's an incritin hormone, meaning it's released after we eat and helps regulate insulin and energy metabolism. Think of GLP1 and GIP as two different members of the same metabolic communication team. They both help coordinate what happens after we eat, but they each bring slightly different strengths to the job. Think of today's GLP1 medications as pulling one major lever in metabolism, while Reditrutide is trying to pull three at the same time. And the early weight loss data with Reditrutide has been remarkable. It's giving the kind of numbers that get people's attention very quickly. But here's where my brain goes immediately, of course, and that's if today's medications are already feeling incredibly powerful, what happens when we make them even more powerful? Could they be even more effective? Possibly, but could they also raise new questions? And I think the answer to that is absolutely. Because more powerful doesn't always automatically mean better. Sometimes it simply means we need to think even more carefully about the trade offs. And I think that's where obesity medicine definitely. Definitely is right now. We're entering an era where the question may no longer be, can we make people lose weight? The question may actually become how do we help people lose weight in ways that maximize health, preserve muscle, improve quality of life, and minimize unintended consequences. And I think that's a much more interesting and important question.

Evidence Gaps And Personalized Dosing

Krista 22:20

And when we look at what the evidence is saying, this is where I think humility becomes really important because right now we have lots of anecdotal success stories, increasing clinician interest, observational experiences, thousands and thousands of people experimenting with different approaches. But what we don't yet have are large randomized trials, long-term outcome data, standardized protocols. We also don't have clear guidance regarding who benefits most, clear guidance regarding dosing schedules, or clear guidance regarding maintenance strategies. We're still learning all of this. So one of the biggest questions in obesity medicine right now isn't simply whether GLP ones work. It's whether we can find the minimum effective dose that provides meaningful benefit while minimizing unwanted trade-offs. And that is personalized medicine. That's individualized medicine and thoughtful medicine. And I suspect that's where this field may ultimately be leading, which is super exciting. Because maybe the future isn't maximum appetite suppression. Maybe it isn't full dose forever. Maybe the future looks different for a lot of different people. Maybe some people need full therapeutic doses, and maybe some people benefit from lower doses. And maybe some people require long-term treatment, but maybe others don't. The truth is we're still learning about all of this. And I think this section beautifully captures the entire theme of today's episode. And that is that GLP1s may be one of the most promising and also the most disruptive therapies we've seen for obesity, but it may also be one of the most complicated. So I think it's okay to be excited and I think it's okay to be hopeful, but I also think it's okay to ask a lot of thoughtful questions while we continue writing the rest of this story.

Respect The Power Avoid Extremes

Krista 24:03

So in closing, should we be scared of GLP ones? I'm not sure. But I do think that we should definitely respect them. I think we should ask lots of questions. I think we should individualize decisions. I think we should avoid extremes because I don't believe these medications are evil and I don't believe they're magic either. I think they're really powerful and powerful therapies deserve thoughtful conversations. For some people, these medications may absolutely be life-changing. And if you're that person, I hope that's the case for you. For others, they may not be the right answer. And I think that's okay. So the question isn't whether GLP ones are good or bad. The question is for whom, under what circumstances, and at what cost. And perhaps that's the biggest lesson of all. Obesity is far more complicated than we've been led to believe. It's not simply eat less, move more, try harder. There's biology involved, psychology involved, environment involved, behavior involved. And perhaps that's why GLP ones have captured so much attention, because for the first time, millions of people feel like someone is finally acknowledging that obesity is way more complicated than lack of willpower. I understand why people are excited. I understand why people are hopeful. And I think that's okay to remain curious, to ask questions, to be thoughtful, because medicine is rarely black and white, and the most responsible place to live is usually somewhere in the

Medical Disclaimer And Personal Support

Krista 25:30

middle. So as we close out today's episode, please remember that everything shared on Serenity and Fire is meant for general information and inspiration purposes only. The topics we discuss are not intended to diagnose, treat, or replace personalized medical care. So please always consult with your healthcare provider regarding your individual healthcare concerns, laboratory results, medications, and treatment decisions before trying anything we talk about on the show. Your health is unique and your care should be too. So as we wrap up for today, I want to remind you again that my goal on Serenity and Fire, and of course at Panacea Luxury Spa Boutique is to help you create a life where you can function better, age differently, do more, and remain fully engaged in the people and experiences you love most. So if there is ever anything I can do to help you reach that goal, please message into the show and let me know. I really, really do love hearing from you. And as always, thank you so much for listening to Serenity and Fire.

Follow Share Review And Final Signoff

Krista 26:25

If you are enjoying the show, please definitely follow me on social, leave a review, and share my episodes with those you love most. Until next time, protect your peace, always lead with integrity, and keep balancing serenity with fire. I'm Krista Guigenny, and I'll talk with you more in our next episode. At

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Krista 26:44

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