B (3:42)

Thanks, Neil. I'm so excited for this discussion today. It's such a relevant topic I see every day in the office. This should be great.

A (3:49)

Thanks. Next, Let me introduce Dr. John Hertig. Dr. Hertig is an associate professor in the Butler University College of Pharmacy and Health Sciences and department chair of Pharmacy Practice. He is a member of the Editorial Advisory board for the Joint Commission Journal on Quality and Patient Safety. He also holds advisory roles with the U.S. food and Drug Administration and the Patient Safety Workgroup of the International Pharmaceutical Federation. Welcome, John.

C (4:20)

Thank you, Neal. It's a pleasure to be back and looking forward to this discussion.

A (4:25)

And finally, and perhaps most importantly, let me introduce Lisa Kessler, who will share with us her perspective on this and as a patient. Lisa, welcome to Ada's podcast and can I ask you to introduce yourself so you can put your thoughts into whatever context you think is relevant for our discussion? Lisa sure.

D (4:48)

It's a pleasure to be here. My name's Lisa Kessler. I've been a patient of Dr. Skolnick's for going on 25 years and I'm 65 years old.

A (4:58)

And Lisa, I just again want to say how much I appreciate your joining us. Can you share what went into the decision about starting a weight loss medicine for you?

D (5:10)

Yes, I had scheduled a visit with Neil, which I do annually, and typically ask for my blood work to be drawn before I meet with him. And I got to review the blood work before meeting with him because it came up on my patient portal and I was a bit surprised to see that my A1C was elevated as well as my liver enzymes. Being the age I am and also with a diagnosis of Hashimoto's, I've always made excuses as to why I wasn't dieting enough or working out enough, but I truly was trying and I just couldn't get that weight off. And now that I saw the blood work, it really scared me. My father is a type 2 diabetic and I didn't want to follow in the same path. I understood that there were these new medications available and I wanted to discuss it with Dr. Skolnick at our appointment.

A (6:09)

And Lisa, we've known each other for years and I know how much you've paid attention to your health over many years. 1 I know that you've worked out. You do exercise, you watch your diet, and it was pretty clear that that's been healthy. But that wasn't enough, right?

D (6:29)

Absolutely. I thought I was doing enough. And you were always educating me as to what I needed to do, and you were always understanding and just pushed a little bit more. And I truly was doing the best that I could.

A (6:43)

And I think that's so important because we've learned a lot over the last decade, really, about obesity as a disease. We've learned that, and you and I had talked about this, that there are all these hormonal shifts that occur that make it not a failure of will, as we used to think, but rather it is a chronic disease and needs to be addressed as such. So, Lisa, having thought about this once you saw those labs and having tried your best for a long time, what was your next step? You were thinking about starting a weight loss medicine. What was involved in that decision and how did you go about approaching that decision?

D (7:24)

To be honest, I was surprised that you had broached it because I thought as a physician, my father was a physician, that it would be just keep working. That's what I had heard from my endocrinologist. And, and I. It's just one of those things repeated from doctors. You're not working hard enough at it. Let me give you some help. Let me get you a nutritionist, a dietitian to help you do this more. But I was very happy that when I did come to the appointment, you brought it up. I was really thrilled because I thought, oh, good, I have someone who knows me and knows that I have been concerned with my health and you've been following me and that I really was an educated patient and would be willing to research this medication on my own, as well as listen to your suggestions and to be able to do something more about it to make myself healthier.

A (8:20)

It's interesting, Lisa, when you say that, and we'll get to our main topic, which are compounded medicines, in a moment. But as you say that, it really is a reminder to me how important it is for us as clinicians to proactively talk to our patients about obesity as a disease and that there are medicines available, because if we don't, you are full aware. I didn't realize how you thought. I wouldn't encourage you to think about medicines, and that must be going on all over. And then people, when they're not encouraged, probably go to the Internet to look for what the options are out there. Sue, you have some thoughts?

B (9:00)

This story is so fascinating to hear, because in my career thus far, no other medicine has been so ingrained in the social culture of what people are experiencing in their everyday lives. And so I think it's really interesting that these patients come to our office and they have already thought about this, they've done their research and really are coming in ready to make a very informed research decision in most cases. And this is really different than a lot of other medicines that we talk to patients about. And I. I think it really highlights that.

A (9:34)

It sure is, John.

C (9:36)

Absolutely. And I'm just listening to this really wonderful story. And for me, I think what shines through is that, Neil, you have this excellent relationship with Lisa, and vice versa. So it speaks to the nature of a patient physician relationship that's so important, or a patient pharmacist relationship that's so important, because what that does then is enable that dialogue that's so critical to ensure that we're making healthy choices for each other and for our patients.

A (10:00)

That's a good point. Now, Lisa, I'm curious. Prior to our beginning that discussion, were you also thinking about if we didn't prescribe weight loss medicines in the office, were you thinking about looking into medicines elsewhere, whether it's on the Internet or through some other clinic?

D (10:19)

I have a neighbor here who was using a diet doctor, and he had been talking to me about his experience. And I also had been speaking to two other friends that had already used the Internet, one who only had to give a blood test, the recent blood test, and spoke to a nurse practitioner and was sent the medication. And then I spoke to someone else who simply went online, didn't need to provide a blood test or speak to any medical professional, and was sent the medication. What made me stop looking at that point was they all said that their compound medication was coming from a compound pharmacy in Hallandale, Florida. And I thought, how is that possible? That a physician is getting it from Hallandale and a nurse practitioner is getting it from Hallandale? And then this person who didn't have to do anything or talk to a medical professional is getting it. So I was very confused, but it put up that red flag of what's going on here. I know the FDA, because of the shortage of GLP1s, the FDA was allowing compounds. But I also knew there was no oversight. So I thought, what's going on? Are these people telling the truth? Is this a legitimate pharmacy? Is it really coming from this pharmacy? And that's when I thought, I trust Dr. Skolnick. I'm going to go and have my visit and hopefully if you weren't going to bring it up, I was going to bring it up because I was scared and I trusted you. I didn't trust all of these other relationships.

A (12:02)

Boy, that's interesting, Lisa, as I listen, I get a little scared because not everyone is as inquisitive as you are or as careful as you are. And I'm curious, when you looked at those sites, it seemed, I imagine, easy to get the medicines. If you didn't even have to talk to a clinician or get blood work, it was easy. It's no secret that these are not inexpensive medicines. Was there an attractiveness to the fact that it was less expensive through these sites?

D (12:35)

Absolutely. My friends were paying varying amounts. One with a physician was paying mid-500s, one with the nurse practitioner was paying a monthly fee and in the three hundreds. And the other one that had no medical professional or blood work, she was paying in the three hundreds. So here I was luckily able to get a few months of coverage from my insurance company. They covered for three months and then I had to use a Lilly coupon, which I had to pay half price. But then I was turning 65 and going on to Medicare and I remember having a discussion with you, Neil, where I said, this is really expensive. I'm going to be turning 65. I wanted to rush and start doing it and you stopped me and you said, we really need to have a discussion because this is not something you go on for a few months and stop. And you had that discussion with me that it's not about what you can afford for a short period of time. It was a long term commitment. And you asked me if I was able to do that financially. That's when the compound, of course, sounds more affordable than the true GLP1 medications.

A (13:53)

Yeah, these are big decisions. There's that old expression you get what you pay for. And it's an old expression often repeated because there is a truth to it. John, I'd be interested in any thoughts you have about what Lisa's describing, her friend's experience about how easy it is to find compounded medicines out there through the Internet.

C (14:19)

Sure, yeah. Happy to elaborate a little bit here. We've, we, including my research team, have done years of research on Internet pharmacies, e commerce, the availability of really any medication online. And it can be a really scary environment. You now couple that with the real explosion of the, the popularity of GLP1s and what you have is certainly a subset of compounders that are legitimate. We'll talk a little bit more about that, Neil, here in our discussion. But what you really have is this explosion in people compounding or groups compounding sterile products that really have no business doing so because they see it as a way to make money quickly, as a way to use e commerce platforms to access patients in new ways. And so you have this really big demand on the patient side and you have this really huge exponential increase in compounders that maybe are a little unsafe or maybe aren't doing it the right way or maybe don't have the right level of oversight. And that creates a real patient safety concern for myself and some of you all and other colleagues that are dealing with this type of issue.

A (15:20)

Yeah. And from a patient point of view, and I've gone online and browsed around, it's impossible to tell what's what. Sue, I'm interested in your thoughts here. I know patients ask you for advice on compounded medicines. What has gone into formulating your thinking here and what's your perspective on this issue?

B (15:43)

Yeah, it's been really interesting and I've certainly learned a lot. But I think the first point is patients ask about compounded medications for a variety of reasons and I think it's really important to explore that. Right. Are they having availability issues? Are they not sure about insurance coverage? Did they join a group weight loss program that's offering it? Right. There's lots of different reasons that people are looking at compounded medications. I always do share my concerns. I think the concern about counterfeit medications and my experience in seeing patients with highly variable unreliable dosing in compounded products. And I share that experience with them and tell them I don't recommend compounded products. I'm just not comfortable enough that the safety is there. But the other thing I explore with them is lots of these patients might actually qualify for prescription coverage of their medications, but they're not aware of how that process works. So even if their insurance doesn't cover them for weight loss, they might cover them for FDA indications like CVA or TIA or MI or newly osa. Right. So there are other medical conditions that we might be able to use to get things covered by patients insurance. And I think in general as clinicians, we really do need to have comfort with our local insurers with the prior AUTH process. What requirements are needed and help patients reach out to their insurers, help our clinical staff understand the process. In our office we meet regularly with our clinical prior AUTH staff. It is the new year brings all of these new requirements right so we're meeting, we're talking about it because I think that's our way of helping patients access these medications. And then we don't have this uncomfortable situation where they're reaching for combative meds because they can't get prescription meds. So it's one way, I think that we can help them. So I go through all of those questions and really try and see, are there other ways that I can help them get these tremendous medications.

A (17:36)

Wonderful points, Sue. When you share your perspective and you said just very clearly you're uncomfortable with the idea of the compound of medicines, how do patients respond to you?

B (17:48)

Yeah. There's no doubt that these medications can be life changing. I am a big believer in shared decision making. Every time I meet with a patient, we are having open, honest, back and forth conversations about whatever it is we're talking about. This conversation or dialogue is not uncommon for my patients, and I think they appreciate a good discussion. I think what I do, though, is share some of even my relevant clinical stories of just last week, Right. A patient who was using compounded medication. They couldn't find starting doses, and they're like, okay, I'm ready. I can find this prescription dose that's going to cover it. Really. I was down and out for over a week. Right. Needing medications for nausea, for vomiting. Right. And just trying to share these stories that I have just to explain to them where my concerns really lie and what their true consequences are. But ultimately, at the end of the day, my patients are going to make the decision that they feel is best for them. And it's likely that if they have side effects or problems, they're reaching out to me too. Right. So I would much rather be a partner in whatever they decide to have open and honest conversations, but also be available and supportive of them in whatever their decision is. Right. We still have this relationship. We're still building our relationship. And so again, I think it really comes down to that shared decision making that we do with all of our patients all of the time.

A (19:11)

That's so important. And that approach really facilitates that long term relationship, the trust that's so important that allows patients to take our advice in the way it's intended, which is to help them. Lisa, your thoughts?

D (19:27)

Yes. What I learned, because of the friends that weren't being followed by a physician, I was able to go see Dr. Skolnick on a monthly basis to decide are we going to change the dosage? But also, he educated me so much about my diet and what I should be eating, proteins, what I should be looking out for what I should not be eating, how much I should be exercising. And without going to a physician for this and going online, I would not have gotten any of that information. And I found myself actually sharing this information with the people that were going online for the compounds, whether counterfeit or legitimate, because they weren't given that information.

A (20:10)

That's such a good point, Lisa, because sometimes we forget that it's not just about taking the medicine and it's not just about losing weight, but it's about being healthy. And the way to achieve optimal health with the help of GLP1 and GIP, GLP1 dual agonists is to have it as part of a larger picture that has health related counseling as a part of it. The importance of exercise, both aerobic and resistance exercises. Back almost a year ago now, we had a series on obesity. Sue, you were a part of the episodes of that series where we talked in detail and again, I'll refer our listeners to it about the advice that needs to be given when you're giving a GLP1 and the importance of enough protein in your diet, the importance of resistance exercises as a part of using these really critically important medicines to help us achieve optimal health outcomes. Now, John, can I ask you, do pharmacists get asked about this issue, compound medicines by patients?

C (21:27)

Yes, Neil, absolutely they do. And I just so appreciated sue and Lisa's commentary. And as another real vital member of the care team, pharmacists do play a pivotal role here. And we are the medication use experts, and we're often confronted with these issues not only in a community or ambulatory care setting, but also in the hospital setting. Ultimately, pharmacists are engaging with patients and committed to ensuring that no matter what medication that patient taking, that it's both safe and effective. And as we've detailed in both this podcast and in previous podcasts, we can't always assume that compounded medications, especially those GLP1s purchased online, are both safe and effective. So having that transparent conversation with patients is absolutely critical so that they understand the risks associated with purchasing medications from either verified or unverified sources. Patients need that education so that they can be armed with every piece of knowledge at their disposal before making a decision on their health. And pharmacists are just another piece of that healthcare puzzle to help them make really good choices.

A (22:30)

They are. Can you summarize for us what you feel are the most important issues for us as clinicians to be aware of with first compounded medicines and then counterfeit medicines. And can I ask you to distinguish between the two because I do think there's concern, confusion out there.

C (22:47)

Absolutely, let's start there. Let's start with this difference between legitimate compounded and then counterfeit medications. So our legitimate medications are those that are either from manufacturers or even from compounders. So most manufactured FDA approved medicines are from that FDA verified manufacturer, whether it be an Eli Lilly or another company. Compounded medications I'll get to in a minute. But counterfeit medications are just fake. They're in no way intended to treat anything. If you look at the World Health Organization, they have a little bit different of a definition. They would call that substandard and or falsified substandard meaning of lower quality, meaning it doesn't contain any of the active pharmaceutical ingredient or maybe not the right amount of pharmaceutical ingredient, it's just a bad product. And then we have falsified where it's, they're lying about what it is. So it's like saying I'm a, oh, but I'm not ozempic at all. They're just false advertising. So that SF substandard falsified is what we would maybe call counterfeit in the United States. This is criminal activity. It can be really dangerous for your health. And unfortunately many of these online actors, these online pharmacies, and I'm using air quotes, are selling these counterfeit products and patients are the ones getting harmed both through their health but also financially because now they're putting all a lot of money into these products that are essentially fake. Now if I go back to this idea of compounding, I think it's important because compounded medicines do serve a niche within our healthcare systems. Clinicians and allied practitioners in the community, hospitals, clinics and other healthcare facilities sometimes do request, prescribe or even provide compounded drugs to patients when the FDA approved drug is not medically available or appropriate. So in these situations which are very specific, compounding can serve an important patient needs. For clinicians though, it's really important that we understand there are some regulational difference here, some regulations that are different. Your local pharmacy, the one that brick and mortar down the street, often operate what's under section 503A of the Food, Drug and Cosmetic Act. So that's when you receive a very specific prescription for a patient that needs a very specific medication compounded, maybe something that because that patient can't swallow, needs to be liquid or maybe some type of additive or flavoring. These pharmacies down the street are regulated by the states. Now compounders may also provide compounded versions of a drug on the FDA's drug shortage list. And that's what we had seen with both semaglutide and tirzepatide. Now, tirzepatide has been pulled off that FDA drug shortage list. But if it's on that FDA drug shortage list, those bigger compounders can make big bulk ingredients or bulk versions of that as long as they meet certain conditions under federal law. But they are not FDA approved. And I think that's the crux of our conversation here. That means that the FDA does not verify the safety or effectiveness or quality of those compounded drugs before they're marketed. Those larger compounding pharmacies make them in bulk. They need to comply with what's called CGMP or current good manufacturing practices that are in the conditions of 503 of the food, Drug and Cosmetic act, but they are not FDA approved. They should register with the FDA as what's called outsourcing facilities. But again, the regulations here can be tricky. And you have this huge increase in sterile compounding because of this demand for GLP1. So you have these compounders that have just sprung up that probably have no business actually making sterile products for patients.

A (26:20)

And that idea of sterility here is so important because this clearly it would be important if it were medicines that we were ingesting orally. But when you're injecting something, sterility and the carefulness that has to go into it is so critical. We're almost out of time. Lisa, can I ask you if you have any final thoughts you'd like to share with our listeners?

D (26:44)

I'm just thankful that I have you as a physician to be able to guide me. And again, you did discuss compounding and how you felt about it. And I'm just glad that you educated me and I was able to make the decision based off of your education and also my snooping around the Internet. And I've lost the weight and I'm happy and I'm healthy and my blood work looks good. And that's what this should all be about. But doing it in a healthy manner, being supported by your physician.

A (27:13)

Yeah, and I think you're right, Lisa, and that gratitude goes in both directions. So having taken care of you for so many years, it felt so satisfying for you to come in and ask questions and to be able to work together. And that's really, I think, a model for what we all ought to be doing in primary care. And sue, you alluded to this. The shared decision making with patients, the ability to have an open door so we can engage in those ongoing discussions builds trust. John, any final thoughts you have for our listeners?

C (27:50)

Yes, thank you, Neil. I just think this is a total back to the basics conversation where if you are a patient, talk to your physician, talk to your pharmacist. If you're a physician or pharmacist, talk to your patients. Right. We need to be engaging with dialogue on this issue and ensure that our patients and everyone understands not only what they're taking, but where that medication comes from. That's never more important than today, particularly with GLP1s, because there are many safe sources that do provide effective medication. And we as clinicians need to ensure that we're directing our patients to those trusted and verified sources. All too often, pharmacists, physician nurses, and other allied health care professionals are not counseling our patients on how to obtain these medications safely. And so there's a real urgent need, especially with the increasing use of the Internet to obtain medications, medical products, and, unfortunately, medical misinformation. So I just want to continue to encourage my clinical colleagues to ask their patients, where do you get your medication from? It's a great way to open the door to a really important and vital conversation.

A (28:53)

Such important thoughts. Sue, your thoughts?

B (28:56)

Yeah. And I think what I've taken away from what everybody has said is, like, what a wonderful time for clinicians and patients to be engaged with each other. Right. As a primary care doc, when somebody comes in and they're really engaged about their health and they have all of these questions, I really love that we're at this point with these medications spurring on these discussions, which I think is great. And we need to be really careful that we're not going so fast and moving so fast that we're putting safety aside. And I think that's really the give and take of these conversations, conversations with patients. But at the end of the day, I love that people are coming in to talk to me about it. I think that's wonderful.

A (29:34)

Fantastic. Sue, thanks for sharing those thoughts. And sue, thank you so much for joining us.

B (29:40)

So happy to be here.

A (29:41)

Lisa, thank you so much.

D (29:44)

Thank you for having me.

A (29:46)

And John, of course, thanks for joining us again.

C (29:49)

It's been a pleasure. Thank you.

A (29:51)

Most of all, of course, thanks to our listeners for joining us for this discussion of compounded and counterfeit GLP1 and GIP. GLP1 receptor agonists. A clinician's and patient's perspective. I'd like to remind people that for more information on this topic, I've put links in the show notes to one of the FDA statements and to the American Diabetes Association's position statement on compounded GLP1 and GIP GLP1 agonists. In this statement, the ADA has said, and here I'll quote compounded GLP1 receptor agonists and dual GIP GLP1 receptor agonist products are not identical to the FDA Approved products. Compounded GLP1RA and dual GIP GLP1RA products have been associated with clinically important dosing errors and adverse events. Counterfeit products have made their way into the US Drug supply chain and have been advertised online and by unregulated sources. The ADA statement summarizes the position of the American Diabetes association stating, and again here I'll quote briefly, Non FDA approved compound and counterfeit products are not recommended for use due to uncertainty about their content and resulting concerns about safety, quality and effectiveness. I hope this discussion was helpful in putting this issue into perspective in helping all of us advise our patients on this critically important public health issue. This special edition of Diabetes Core Update is sponsored by Lilly for the American Diabetes Association. I'm Dr. Neal Skolnick. Till next time, stay safe and keep learning. It.