Disclaimer: This podcast is for informational purposes only and is not intended to be used as personalized medical advice.

Melanie Cole, MS (Host): Welcome to Be Well with Skagit Regional Health. I'm Melanie Cole. And today, we're talking about GLP-1s for weight loss. Joining me is Jaya DeElena. She's an advanced registered nurse practitioner and family medicine provider at Skagit Regional Health.

Jaya, thank you so much for joining us today as we get into this topic. And wow, it's a real hotbed topic. Why is it important to recognize obesity as a chronic disease rather than viewing it as a matter of willpower? Because it is recognized now as a disease. It's an epidemic, and we're seeing it really all over. Tell us a little bit about why that's so important.

Jaya DeElena, ARNP: Thanks for having me today, Melanie. So, in that context of looking at overweight and obesity in medical terms, overweight, we use a measurement called BMI. So, overweight would be a BMI of 25 to 29.9. Obesity, by definition, is a BMI of 30 or higher.

So, BMI is a useful screening tool, but it's important that we know that it does not tell the entire story. It does not directly measure body fat, muscle mass, where fat is stored or an individual's overall health.

So, medical professionals will consider other factors like waist circumference, medical conditions, medications, family history, lab results and overall health when we're evaluating an individual's health and determining what treatments are appropriate. So ultimately, in medicine, the goal is never to place a label on a person, but the goal is to understand the health risk and of course, provide compassionate, evidence-based care that's tailored to the individual.

I think a really important thing to understand about obesity is that genetics play a fairly significant role. In fact, research suggests that genetics differences account for roughly forty to seventy percent of the variation in BMI that we see in the general population. This does not mean that 40% to 70% of a person's weight is determined by genes, but what this means is a person's genetics can strongly influence a person's tendency towards gaining weight.

So, we have to think of genetics as influencing the body's starting point and its response to the world around us. So, genes never act in isolation. It's our environment and everyday experiences that influence how those genetic tendencies affect our health. And these factors, looking at obesity and overweight, they include things like diet, alcohol intake, physical activity, sleep, stress, mental health, medications, and really important, access to healthy food and safe places to be active. All in all, the main important lesson here is weight is influenced by so much more than willpower. So, when we discuss overweight obesity and weight management in primary care, we definitely recognize every person's situation is different. Genetics, biology, environment, lifestyle, medications and other health conditions all contribute.

Melanie Cole, MS: Well, that was such a comprehensive answer, Jaya. Thank you so much. You really explained it well, because I think there's a stigma and people don't understand and recognize this as a chronic disease. And like you said, there are so many misconceptions. Now, let's talk about GLP-1s. Many people know them as weight loss medications. Tell us a little bit about them. What are they and how do they work in the body?

Jaya DeElena, ARNP: Yeah. So, the GLP-1 agonists that we know today, there's some big names. And I'm going to go over those. And they get really confusing because one drug can have many names. So, I'm going to give two examples. Semaglutide is an example of a GLP-1, but it's also commonly known as Ozempic and Wegovy.

Another example is tirzepatide, another very common GLP-1 medication, but its other names are Mounjaro and Zepbound. So, everyone always asks why are there different names? So, the different names when we prescribe this is for what we're treating. So, for instance, semaglutide, when we prescribe Ozempic, which is semaglutide, that's for diabetes. But when we prescribe Wegovy, which is also semaglutide, that's for weight loss. Similarly, the same is true for tirzepatide. When we prescribe Mounjaro, that is for diabetes. But when we prescribe Zepbound, that is for weight loss. And we actually, interestingly enough, also use Zepbound for sleep apnea treatment as well.

So, the story of GLP-1 medications began long before the medication we know today. So, scientists have been studying GLP-1s for a century. And it started with this idea that the gut is not simply a digestive organ. It's also a powerful communication center that influences the rest of the body. So, in the early 1900s, researchers began discovering the digestive system produces chemicals that produce signals that affect other organs. What happens in the gut after we eat can directly influence how the body manages blood sugar.

So, by the 1980s, 1990s, researchers identify and begin studying a particular important gut hormone called glucagon-like peptide-1, also called GLP-1. That's why the medications are called GLP-1s. So, the GLP-1 hormone turns out it does much more than help stimulate insulin release. It also slows the movement of food out of the stomach, and it sends signals to the brain that contribute to feeling full.

There's just one major problem with the GLP-1, this awesome hormone that they identify, and that is it doesn't stick around in the body for very long because the body breaks it down really quickly. And this made it really difficult to use the hormone itself, the GLP-1 hormone itself, as a long-lasting medication. So, science faces an important challenge at this point in time. And the question is, can they turn these promising findings into a practical treatment by creating a version of this hormone, GLP-1, that can provide benefits while lasting much longer in the body?

Since the early 2000s, researchers continue refining this approach. Now, we have newer medications that have been engineered to last much longer, which is why many of these injections are once-weekly injections. And they also discover a GLP-1 is only part of the story. There are newer medications like tirzepatide, which are also called Mounjaro and Zepbound that target multiple hormone pathways. And this actually produces broader effects on blood sugar, appetite and metabolism.

So, what starts out as research into how the gut communicates with the pancreas has evolved into an entirely new approach to treating chronic diseases, including obesity and overweight. The GLP-1 based medications are typically used to help manage type 2 diabetes, but we are seeing a huge increase in their treatment for obesity. But their effects extend well beyond blood sugar and weight. So, depending on the specific medication and the individual patient, research is even demonstrating benefits in the cardiovascular system, kidney outcomes, and again, as I mentioned before, sleep apnea.

So, I feel like the evolution of these medications is really remarkable and a great example of how medical discoveries first often take sometimes decades to build. And what begins as a simple question ultimately leads to medications that have great influence over health in general, including appetite, metabolism, blood sugar, as well as other organ systems. And I think perhaps, most importantly, is we're still learning just how far these medications can go.

Melanie Cole, MS: Well, you mentioned a few of them. So, beyond weight loss, what are some of the health benefits that GLP-1s can really potentially provide? I mean, it is certainly an exciting time in this field. So, tell us a little bit.

Jaya DeElena, ARNP: So, one of the most exciting developments in the GLP-1 research has been the discovery that some of the medications in this class can provide cardiovascular benefit. That's heart benefit. So again, going beyond be-beyond the effects of blood sugar and weight. GLP-1 medications in research studies show that there's possible improvement in the health and function of blood vessels, including helping the blood vessels relax, which then allows the blood to flow more easily.

They can also contribute to lower blood pressure. Part of that is through the weight loss and changes in the body's nervous system activity. So, for people at increased heart risk, these effects can be really important. In fact, there's been large clinical trials that found that certain GLP-1 medications can reduce the risk of major cardiovascular or heart events, including non-fatal heart attacks, non-fatal strokes and cardiovascular death.

For example, liraglutide, which is a GLP-1, what has been shown in research studies to reduce major cardiovascular events in people with type 2 diabetes who were at high cardiovascular risk. Semaglutide, that's also known as Ozempic and Wegovy has also been shown to reduce major cardiovascular events in adults with obesity and established cardiovascular disease.

And we've also seen the GLP-1 medications in people with heart failure who have preserved ejection fraction. And we see that there are improvements in symptoms from heart failure, physical limitations and exercise capacities when the GLP-1 treatment is included. We also see that GLP-1 based treatments are currently being studied for the potential to reduce heart failure-related hospitalizations, which is really awesome.

Another area that the GLP-1s have benefit are the kidneys. The research is showing very promising benefits. So, diabetes is one of the leading causes of chronic kidney disease, and controlling the blood sugar is an important part of protecting kidney function. We have studies that show the GLP-1 medications, including liraglutide, dulaglutide, semaglutide, have found reduction in certain kidney complications, particularly those related to diabetes.

Some of the kidney benefits may come indirectly through better blood pressure control and weight loss and improved blood pressures. But researchers believe that the GLP-1 medications may have direct effects on pathways involved in the kidneys. So, this evidence has become strong enough that semaglutide has an FDA-approved indication to reduce the risk of sustained decline in kidney function, end-stage kidney disease and cardiovascular death in certain adults with type 2 diabetes and chronic kidney disease.

And lastly, we see the GLP-1 agonists being used in sleep apnea. I mentioned earlier that tirzepatide also known as Zepbound. The Zepbound is the tirzepatide that is used for sleep apnea. It is the only FDA-approved GLP-1 medication for sleep apnea. And the medical evidence shows tirzepatide reduced obstructive sleep apnea severity in patients with obesity, primarily due to weight loss associated with the medication.

However, the medical evidence also found on the observed cases, patients who were using tirzepatide had a decrease in a measurement that sleep medicine uses called the apnea-hypopnea index. And this is a measurement that we use during sleep studies to determine how often a person's breathing is interrupted or reduced while they sleep. So, we find that on average a decrease in this AHI number.

So, it is important to note in the sleep medicine research, CPAP remains superior for decreasing these AHI events including daytime sleepiness, where the GLP-1 medication primarily improves the weight and glycemic indices.

So, most sleep medicine specialists recommend the integrated use of both CPAP and the GLP-1 medications. The story of the GLP-1 medications is much bigger than weight loss. Again, we're seeing it in heart health, kidney health and even part of the treatment for sleep apnea.

Melanie Cole, MS: Jaya, who might be a good candidate for these medications? Tell us a little bit about some of the factors and patient selection criteria. They're not for everyone. So, how do you determine whether they're the right option? How do you work with patients in that shared decision-making?

Jaya DeElena, ARNP: Yeah, that's a great question, Melanie. So, patients with obesity, sleep apnea and diabetes are excellent candidates for these medications. There are patients that fall into certain categories that should not use this medication, and that includes patients with a history or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2. That's abbreviated as MEN 2. These are not appropriate for pregnant or breastfeeding patients. This is not appropriate for patients that have severe gastroparesis. It is not appropriate for patients who are allergic to the drug or drug component. And it's not appropriate for patients who have severe kidney disease.

Melanie Cole, MS: Well, thank you for that. And realistically, when people are thinking about this medication for weight loss and treatment, including how long it may take to see results, outcomes certainly are going to vary from person to person. What are realistic expectations when you're working with patients? What do you tell them?

Jaya DeElena, ARNP: Absolutely. So, as with all medications, results will vary. The research evidence informs a general idea of the results that can occur, but people aren't textbooks. They're not research studies. Every person and their bodies are different. So, when we're looking at the research evidence, with weight loss specifically, it depends on the medication that is being utilized.

A patient can expect to lose anywhere between 5% to 20% of their weight over a period of anywhere from six to18 months per the medical evidence. Typically, we see the weight loss is more rapid in the first approximately six months. And then it slows down, eventually plateauing around 19 months. We do see that tirzepatide, Zepbound, again, those are the same medications, is associated with the most weight loss, followed by the use of semaglutide, also known as Ozempic; then liraglutide, also known as Saxenda.

Melanie Cole, MS: What are the most important side effects? I mean, we see the little insert when we get these kinds of medications, and it's always something that is discussed. Speak a little bit about the important side effects, the risks, the costs or limitations that you really feel patients should discuss with their healthcare provider.

Jaya DeElena, ARNP: The most side effects are typically mild, and they will occur during the first few weeks of treatment, especially when and if your dose is being increased. But these tend to improve over time. So, most side effects that occur are nausea, which is the most common side effect, vomiting, diarrhea, constipation, stomach pain or bloating, decreased appetite, heartburn or belching, fatigue or headache, and sometimes injection site reactions, including redness, itching or mild pain at the injection site.

So, if we recall earlier, I mentioned that these medications work heavily in the gut, slowing movement of food through the gut, which is why we see a lot of GI side effects. The GLP-1 medications are highly effective. But again, there are side effects and risks that can be increased when we use them. So, we have to be careful with patients who've had a history of pancreatitis. So, patients who've had a history of pancreatitis may require special consideration before starting the GLP-1 medication. But it's not a contraindication or a full stop, if you will, that they cannot have the GLP-1 medications. So, we just need to be mindful of those patients.

Another one is the GLP-1 medications, especially when we see significant or rapid weight loss, can actually increase the risk of gallstones and gallbladder inflammation. So, people with a history of gallstones or other gallbladder-related problems really need to discuss this with their healthcare providers.

And again, we have to be careful, because it slows the rate of emptying through the stomach, we have to be careful with people who have certain GI stomach and digestive issues because these do slow the movement of food through the stomach. This is one reason they can help people feel full longer, but it can also be a concern for people who already have significantly delayed stomach emptying, chronic severe nausea or certain GI problems. So, people with a history of gastroparesis, that's when the bowel just really doesn't want to move or other types of gastric surgery, they will need to consult a provider before starting it.

The GLP-1 medications are generally not substitute for insulin in people with type 1 diabetes. And we have to be very careful in this population. And if you take other diabetes medications like insulin or diabetes medications like sulfonylureas, like these are commonly known as glipizide or glimepiride, and we add a GLP-1 medication, this actually can increase the risk for something called low blood sugar or hypoglycemia. And it can get dangerously low, so we have to be careful.

And then, those people that have advanced liver disease or decompensated cirrhosis, they require individualized medical evaluation, because there is limited evidence regarding the safety and effectiveness of the GLP-1 medications. And those people who have diabetes and they have diabetic retinopathy, may need closer eye monitoring when starting the GLP-1 medications.

I will say one important side effect that we see over long-term use with the GLP-1s is muscle wasting. So, the weight loss is not exclusively fat loss. Some of the weight loss during rapid or substantial weight loss can come from lean tissues, including the muscles. The exact proportion varies considerably between individuals, and it depends on factors such as diet, physical activity, the amount and speed of the weight loss and the treatment being used.

This is why maintaining adequate protein intake and incorporating resistance or strength training can be very important parts of healthy weight management plan when you're on the GLP-1 agonist. The goal should not simply be to lose weight. It should be to lose excess body fat while preserving as much muscle and physical function as possible.

So, in terms of limitations, while there's very promising outcomes, there are limitations of the GLP-1 medications. This includes tolerability, weight regain after discontinuation, cost and access, that lean muscle mass that's lost. Limited long-term safety data and practical barriers to adherence.

So again, one of the things that we see are those side effects, those GI side effects like nausea, vomiting, diarrhea and constipation. This is one of the main reasons patients discontinue or reduce the dose. And this can actually impact anywhere from 40% to 70% of those on the medication.

And then, cost and access, which is a huge barrier. These medications can be very costly. They range from twelve to sixteen thousand dollars per year in the US. There are manufacturer discounts that can reduce this price tag to $7,000 to $8,000 per year. And I have found in practice that insurance coverage varies. And when it is covered, it comes with many clinical restrictions or limitations. Now, Medicare historically did not cover the GLP-1 medications for obesity, but they have recently rolled out with the Medicare Bridge Program. This program has made the GLP-1 accessible at an affordable cost of about fifty dollars per month per patient. But this program does exclude those with diabetes, sleep apnea and fatty liver disease. So, if you have any of those conditions, you are not eligible, unfortunately, for that Medicare program. I have found that some Medicaid programs cover the medications, but there are very specific clinical restrictions.

So, I always encourage patients to contact their insurer, determine coverage, as well as understand the specifics to co-pays and deductibles so they have a better understanding of the out-of-pocket cost when we are prescribing these GLP-1 medications. I've had many patients who have called their insurer, have been told it's covered. But when they get to the pharmacy, it costs hundreds or thousands of dollars. And I think a lot of that is that they did not understand their co-pay and/or the deductibles that are associated with their medical plan. So again, I highly encourage all patients to talk with their insurer about this. Because while we are making strides towards increased affordability for these medications, they are still very expensive.

And then, I want to go back in terms of limitations. Going back to that lean muscle loss, it is approximated 10% to 25% of the total weight loss is actually lean muscle mass, which is consistent with other obesity therapies. This isn't unique to the GLP-1s. And muscle mass loss can have really negative health outcomes on older or frail populations. So, we need to use caution when we are using these medications for our elderly, especially with that new Medicare GLP-1 bridge program.

Melanie Cole, MS: Jaya, as we get ready to wrap up, what is one thing you wish every listener understood about GLP-1 medications before considering them, and what should their next step be when they're interested in learning more?

Jaya DeElena, ARNP: The GLP-1 medications are an excellent tool for weight loss, and I highly encourage anybody who is interested in using them as a tool to aid in their weight loss to talk with their primary care provider.

I want to emphasize the word tool. This is one tool in the many tools that we need to have successful, sustained weight loss. When we are pursuing medically supervised weight loss in the primary care setting, it is vital that patients engage in their weight loss programming far beyond the GLP-1 medication itself, and that would include ensuring mindful, healthy eating, as well as regular physical activity, stress mitigation. That means paying attention to our mental health and reaching out for help when we need help with our mental health. That includes ensuring that we're getting restful sleep and reaching out when our sleep is not restful. Again, the GLP-1 is an excellent tool, and in combination with those other tools, people can be very successful with weight loss and really change the trajectory of their overall health.

Melanie Cole, MS: Absolutely great information, Jaya. Thank you so much for joining us and really sharing your incredible expertise for listeners today. And for more information, please visit our website at SkagitRegionalHealth.org. I'm Melanie Cole. And that concludes this edition of Be Well with Skagit Regional Health. Thank you so much for joining us today.