Shireen: In today’s episode, we are joined by esteemed endocrinologist, Dr. Alyssa Dominguez. Uh, she provides an overview of the GLP receptor agonist drugs. Like Ozempic, a medication typically used for diabetes patients to lower blood sugar levels. Now being used as a weight loss tool. Stay tuned. 

Shireen: Dr. Alyssa Dominguez is an assistant professor of Clinical Medicine in the Department of Endocrinology, Diabetes and Metabolism at the Keck School of Medicine at USC. She completed her medical school, residency and endocrinology fellowship training at USC. She’s the course director for the USC Diabetes Symposium and her clinical interests include caring for patients with diabetes and patients with polycystic ovarian syndrome. Welcome Dr. Dominguez. 

Dr. Alyssa Dominguez: Thank you so much for having me.

Shireen: An absolute pleasure. Dr. Dominguez,  jumping right in. Can you tell us a little bit, or tell our listeners, better yet, a little bit about your journey into this field of endocrinology? And then what just really drove you passionately for helping people with hormonal health in particular. 

Dr. Dominguez: Yeah. So my journey into medicine, and then later into endocrinology started really early. My mom went into medical school when I was quite young and I had the privilege of being able to see her go through those steps, go through medical school and especially residency. And later when she developed her career, I really had a chance to see her passion, in terms of taking care of patients. She’s a pediatrician. Just the relationship that she builds with her patients and the care and fulfillment that she gains from that. So even before I entered college, I sort of had pre-med and medical school kind of in the back of my mind. Fortunately going through college, I was able to get into medical school and got into USC, which obviously is where I still am. When I started medical school, I thought I wanted to focus on women’s health. So going into OB/GYN was kind of the first thing that I considered being a sort of primarily women’s health focused specialty. Later on, I experienced some sort of core procedural specialties, like interventional radiology. And I was like, “Wow, this is so cool. I want to do these core procedures too.” But once I got to my third year of medical school, I started going into the operating room, doing procedures and I was kind of like, “I don’t know if this is for me.” And then, starting my internal medicine rotation, when I was a third-year medical student, I was like, “Oh, wow. I really like this process of investigation, thinking through things, talking to patients.” And I realized that was a much better fit for me. Once I kind of made that realization, I came back to some coursework I had gone through during my second year of medical school, in my endocrinology walk, which I absolutely loved at the time. At the time. I loved learning about all the different organ systems that are affected by the endocrine system. Like the thyroid, parathyroid, pancreas, pituitary. All of these very diverse organs that affect the entire body, but are sort of distinct in their individual ways. When I was a second year medical student, I actually went through the endocrinology clinic for an afternoon and saw a patient who had severe Graves disease, which is hyperthyroidism, which makes People have enlargement in their neck, can have enlargements in their eyes, become very sweaty, have a very fast heart rate. And I was like “Wow, an organ dysfunction from just this one small organ in our neck can cause somebody to have all of these different problems and we’re able to help them out with that.” So, once I decided to go into internal medicine, endocrinology felt like a very easy next step for me. I also realized that I love having long-term relationships with patients. I love the sort of investigative aspect of medicine, of looking into things, getting labs, trying to understand what’s going on with the patient, and trying to help them live, sort of, their best life, for lack of a better phrase. Now, in my practice, I see lots of patients with diabetes, polycystic ovarian syndrome, and other disorders. And we focus a lot on like healthy eating, exercise, and medications to help control their blood sugar, help them achieve or maintain a healthy weight, help get them more active. So, one of the things I really like about my practice is that I’m helping people. A lot of times, do the things that they want to do in life. In terms of being more active, being able to do the sort of activities they like to do. So, those are sort of the reasons that I went into endocrine and the things I like about it.

Shireen: Thank you so much for sharing your journey. You know, in this episode, Dr. Dominguez, we’re really gonna focus on, and this is actually gonna be a very interesting episode, so I wanna let the listeners know about this. But, we’re gonna touch on this type of drugs today in this episode and we’re really hoping that you can provide a little bit more light around this type of drug, what it is, and you know, we’ll get into it in just a second. But, I do wanna start off this episode with a disclaimer to say that we’re not endorsing any drugs, we’re not sponsored by any drugs, or any pharma company. This is purely for information. Our entire podcast, nothing is sponsored by any kind of pharma company or anything like that. So, we don’t have that affiliation. But, this episode is really centered around understanding what the hype is about when it comes to this class of drugs, what it’s implications are in the market today, and why this chaos around this drug to the point of it just completely finishing out and what is it that got sold out and folks couldn’t find it for their diabetes. But, anyways, we’ll come to that in just a second. I wanted to start with that disclaimer. And as we go into this episode, again, this episode is not about this specific drug. It is just as what’s popularly known as, is its drug name. But this episode is really about focusing around and getting an understanding around this drug type, and the implications again that it’s had very recently and Let’s get into it. So, with that, Dr. Dominguez, can you provide to us an overview of this drug, which is called Ozempic. There are a bunch of other names and other pharma company names around it. But Ozempic, this drug, first of all, help us understand what is this drug utilized for?

Dr. Dominguez: Yeah, so to your point, Ozempic is just one drug in a class of medications that’s called GLP-1 receptor agonist, which stands for Glucagon-like peptide-1 receptor agonist. To take an even bigger step back, GLP-1 is a hormone that is produced in the small intestine in response to food entering the small intestine. Normally, when we eat, we produce this hormone and it lasts in the body for about 2 to 3 minutes. The effects of this hormone are increasing our body’s sensitivity to insulin, helping with insulin production. It also decreases appetite, increases satiety, and slows gastric emptying. These medications are basically GLP-1 receptor agonists, which allow the effect of this hormone to last for days or even up to a week. So, that’s how this class of medicine sort of works. The scientists who researched this medicine found that it was helpful for diabetes for these reasons, including increasing insulin sensitivity, helping the body produce insulin. So, it’s been a very potent diabetes medicine, which is, I think, has led to some of the popularity. Additionally, it’s been shown to have significant effects on weight loss too, through the effects that I’ve mentioned, such as slowing gastric emptying and increasing satiety. As you’ve mentioned, there’s several different medications that are within this class, Ozempic being one of them. The generic name of Ozempic is Semaglutide. Ozempic is specifically FDA approved for the treatment of type 2 diabetes. The company that makes Ozempic also has, what I sort of call “a sister medication”, called Wegovy. Wegovy is semaglutide, just marketed under a different name and with a slightly different dosing schedule and with Wegovy is marketing specifically for the treatment of obesity. So, it was interesting and a bit surprising to me that Ozempic was the one that got all this big spotlight on it when that one is more of a treatment for diabetes, whereas Wegovy is the one that’s the treatment actually for obesity. There are several other medications in this family too, such as Trulicity, which is also another once weekly GLP-1 receptor agonist. And then, a newer medication to the market called Mounjaro, which is a combined GLP-1 and GIP receptor agonist that even has more potent, both blood sugar can full and weight loss data behind it.

Shireen: That’s interesting. And, so, these drugs were really created for one purpose, which was to really manage those diabetes. And with the effects that it could have is potentially even managing, sort of, weight and really towards weight loss. Now, we’re hearing a lot of, sort of, hype around these drugs at the moment, in the current moment. But moreso, in the past few months. But, what is causing this hype around these drugs? One in my mind, haven’t weight loss drugs been around for a while? And what is so special about this or why the popularity?

Dr. Dominguez: That’s a great question and I think one thing we’re realizing more and more is that obesity is a chronic illness. It is very difficult to treat. A lot of diets don’t work in terms of achieving weight loss and especially, maintaining weight loss. So, I think one of the things that’s so exciting about this class of medications is that they have been shown to achieve weight loss. You know, sometimes as high as 15%, 18%, which are really staggering numbers in comparison to what we’ve seen in the past. So, I think that’s one big reason. There are some other medications, specifically for weight loss, that have been around for longer, but really we don’t see the same magnitude of weight loss with those other medications that we see with this class of medicines called GLP-1 receptor agonists.

Shireen: So, speaking of which, you know, we know that doctors worn some popular weight loss drugs. May increase the risks of complications under anesthesia, for instance. What really differentiates Ozempic and this drug type from other weight loss medications or approaches in terms of effectiveness and safety?

Dr. Dominguez: Yeah, so to your point about the concern with anesthesia, we know that Ozempic and, you know, medicines, GLP-1 receptor agonists in that family. One of the ways that they work is by slowing gastric emptying. When someone is going into a surgery, they’re often told to not eat anything after midnight, so that they have an empty stomach and a lower risk of aspiration during a procedure or a surgery. There have been some case reports that have come out of still finding food in the stomach of people who are using these medications. So, we’re saying “OK, the fasting that we’re asking these people to do, probably because of these medications, is not producing the same result as it did in people who are not taking these medications.” So, there have been some, sort of, different strategies thought about to kind of deal with this. Like, Should we have people just not eat for longer? And there was a recent, sort of, Consensus statement by one of the anesthesiologists societies, recommending that people hold their dose of the GLP-1 receptor agonist before an upcoming procedure. There are some once daily GLP-1 receptor agonists, so you hold that one the day before the procedure. The once weekly dose categories of the GLP-1 receptor agonists, you would hold a week before the procedure. And the thought behind that is to just decrease this sort of food that could be left over in the stomach to decrease the risk of aspiration or any other sort of complications that could occur with the procedure, with potentially having too much food in your stomach. Going onto your other question about potential side effects from other weight loss drugs, there are some other weight loss drugs on the market that have some very different side effect profiles. One of the medications that I probably use second most commonly to the GLP-1 receptor agonist is a medication that’s called Qsymia. This medication is a combination of two drugs. One is phentermine, which is a stimulant medication, and the other is topiramate, which is an anti-confolssent medication. The side effect profile for this one is a little bit different, since phentermine is a stimulant whereas the GLP-1 receptor agonists don’t have that. So, for phentermine, we definitely want to be careful with people who have uncontrolled blood pressure, uncontrolled hyperthyroidism, or may have some negative effects from the stimulant. Another medication that I sometimes use is one that’s called Contrave, which is a combination of Bupropion, which is an antidepressant medication, and Naltrexone. So, a lot of these medications, we need to be concerned about what other medications is the patient taking, what sort of underlying conditions do they have, what sort of other treatments are they receiving. So, for any of these medications, we really need to take into account somebody’s entire health history and the other medications that they may be taking to determine if they would be a good candidate for weight loss medication. And if so, what would be a good and safe weight loss medication to use?

Shireen: Noted. Is Ozempic intended for short term use or can it be used as a long term strategy for weight management? Of course, with the general weight management drugs that we know, there is a dependency that gets created the minute you come off of those drugs. You know, the weight shoots back up. Can you share a little about that? And then also, what considerations should users keep in mind regarding long term use?

Dr. Dominguez: That’s a great question and certainly one that I get asked quite frequently in my practice. My general counseling that I do for people that I’m seeing is that I think of these medications, in general, as a long term treatment for overweight or obesity. There was a study that they did where they put people on Wegovy, the sort of weight loss version of semaglutide, for a year and they lost a quite significant amount of body weight. After that, they took them off of the medication and followed them for a year, and participants in this study gained about two-thirds of the weight that they lost back, after coming off of the medication. So, that’s a discussion that I have with a lot of my patients where we say “You know, this is a really effective weight loss medication. It does seem to work for as long as you’re on it.” And that sort of weight regain tends to be primarily driven by hunger. As we’ve talked about these class of medications decreases hunger, slows gastric emptying, increases a sense of fullness, and helps with reducing food intake. When we kind of take that away, that hunger surges back and I think that’s what makes maintaining that weight loss very difficult. I definitely do have patients where getting off of the medication is a priority for them. So, we have a conversation of saying “Hey, you know, maybe we try to back off the medication slowly and see if we can maintain this weight loss.” But, these medications are so new that they’re isn’t really sort of guidelines on what I would call like an exit strategy for these medications at this point. So, to summarize, I would say, in general, I’d frame this as a long-term medication, but I’m definitely open to discussions with the patients that I see about strategies for trying to come off.

Shireen: Are there any potential side effects or even safety concerns, and like you said, it is sort of new, but do we know of any safety concerns associated with these GLP-1 receptor drugs for weight loss that our listeners should be aware of?

Dr. Dominguez: Yeah, I would say probably the number 1 and most well known because they have that little blurb in all the end of the ads, is the concern about Medullary thyroid cancer. In the rats that they gave this drug to in the trials where they used it, they did see growth in a certain type of cell in the thyroid that leads to a relatively rare form of thyroid cancer called Medullary thyroid cancer. So, certainly, if somebody has a known history of Medullary thyroid cancer, or a rare familiar endocrine syndrome called Multiple Endocrine Neoplasia 2, those patients, I would definitely not use this medication for the risk of Medullary thyroid cancer. So, that, I would say, would be kind of the number 1 contrary indication. There have been some concerns about increased incidents of pancreatitis. So, I tend to avoid this medication in patients who I know have a history of pancreatitis. And then some other concerns that I take into account when I discuss this medication with people would be concerns about, sort of, underlying nausea or gastric emptying issues, constipation, things like that, because these medications are almost certainly gonna worsen those. A complication of diabetes can be gastroparesis where the sort of stomach and intestines kind of slow down. So, if we add one of those GLP-1 receptor agonists onto that, that could certainly make that worse. If I have patients who have very significant, sometimes even debilitating constipation, I’ll say “Hey, this medication is probably not for you.” So, those are sort of the things that I take into consideration when I’m discussing starting this medication with patients. There was one other consideration I also wanted to mention, and that is discussing people who could become pregnant. These medications have not been studied extensively during pregnancy in humans. In the sort of mouse models that they’ve looked at, the mice that received them did eat less during their pregnancy and had smaller offspring. So, a concern is that if someone took this during pregnancy, that they would eat less and potentially have a smaller baby. Again, this has not been studied in humans, of course, but the general recommendation is for these week long GLP-1 receptor agonists are Ozempic or Trulicity, the recommendation is to stop them 2 months prior to conception to ensure that it’s fully out of the system before somebody becomes pregnant. So, that’s a conversation I have with anybody who could become pregnant cause we kind of have a conversation about future pregnancy plans, use of contraception, just to make sure that they’re fully informed about the potential risks or side effects if they were to become pregnant.

Shireen: That’s very helpful and you know, My next question for you is what alternative weight loss strategies or medications might you suggest? You know, we hear a lot about diet and exercise. In fact, that’s what we do at Yumlish, is focus on building that nutrition literacy, building that exercise competence, but outside of that, what other weight loss strategies do you consider for your patients that really individuals should explore before considering something like an Ozempic, or just probably GLP-1 receptor drugs?

Dr. Dominguez: Yeah, that’s a good question and certainly, as you mentioned, diet and exercise are always gonna be a cornerstone of weight loss. But, there are approaches other than medication, and I think you brought up an excellent point about medications in general that kind of once we stop them, you know, they stop working. So, that’s a discussion that I do have with patients and sometimes, within that discussion, we talk about, sort of, more permanent options, in a sense. And what I mean by that are things like bariatric surgery, which have very dramatic effects, obviously, much more invasive, permanent, but that’s something where if there’s a drug shortage, obviously, that surgery is still gonna have been done. And then there aren’t even some endoscopic weight loss procedures that some of my colleagues do, which are not a surgery, but they, you know, it’s just more of a procedure under twilight anesthesia where they go in and do a procedure in the stomach if it’s not a surgery. So, I think weight loss medicines aren’t necessary, you know, the right answer for everyone and certainly, if somebody is concerned about being on medication for their whole life, or has issues with insurance coverage, or the costs of medications, sometimes talking about some of these other strategies is worthwhile in those situations.

Shireen: That’s incredibly helpful. Dr. Dominguez, with all of this information, we are unfortunately turning the end of the episode. Can you tell us how can our listeners connect with you and learn more about your work?

Dr. Dominguez: Yeah, I would say the main place where I’d share, sort of, interesting articles I’d found or events we have coming up is on my Twitter, which is at @DrALDominguez, D-R A-L Dominguez. So, that would be the main place that I’d share, sort of, things that are upcoming for us and articles that I’ve found interesting.

Shireen: Lovely. And thank you for sharing your wisdom here with us. I feel like I know a lot more about these drugs, and we’re constantly hearing about these GLP-1 receptor drugs, and how they’re selling out in shows, and people can hold them. And it’s better to get fact out of all the noise, and I appreciate you sharing that knowledge with us here. And then to our listeners, thank you for joining us for another episode here. You know the drill at this point. Head over to our social media. Head over to Facebook, head over to Instagram, and answer this one simple question: “What are some unique strategies or approaches you’ve discovered that have made a meaningful difference in your progress towards being healthy?” Pretty simple question. Head over again to Facebook, Instagram @Yumlish, find us there and find this podcast post and comment below again with the question, “What are some unique strategies or approaches you’ve discovered that have made a meaningful difference in your progress towards being healthy?” We will continue the conversation there after this episode. Join us on Facebook and Instagram. Dr. Dominguez, it was an absolute pleasure. Thank you so much for your time.

Dr. Dominguez: Thank you so much. It was great to be here.

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