People are microdosing GLP-1s for weight loss. Is it safe?

Some online clinics are prescribing GLP-1 microdoses formulated by compounding pharmacies. Are these drugs safe and effective?

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Ira Flatow?

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• 0:16Flora Lichtman?

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• 0:37Flora Lichtman?

  Hey, it's Flora and you're listening to Science Friday. There's a new trend in the world of weight loss medications, microdosing.

• 0:47Speaker 02

  Micro habits, micro wins, even microdose GLP-1s.

• 0:53Speaker 03

  Micro? I can do micros.

• 0:55Flora Lichtman?

  Online health clinics are promising big results with microdoses of GLP-1 drugs, AKA Ozempic, Wegovy's Upbound. Many source their drugs from compounding pharmacies. And this can get complicated for patients because compounding pharmacies are able to create different doses or formulations which haven't gone through the FDA approval process. So what do we know about the efficacy? Or how about the safety of microdosing GLP-1s? Is there research to back this protocol up? Joining me now are two experts to help sort through what we do and don't know. Dr. Joey Mattingly, a pharmacist studying compounded GLP-1 drugs, including how they're marketed to patients, and Dr. Jorge Moreno,

• 1:39Flora Lichtman?

  an obesity medicine physician. Joey, Jorge, welcome to Science Friday.

• 1:44Speaker 04

  Hi, Flora. Great to meet you.

• 1:45Speaker 05

  Thanks for having us.

• 1:46Flora Lichtman?

  Thank you for being here. Jorge, what does microdosing a GLP-1 mean? Like, is there a standard microdose?

• 1:55Speaker 04

  Yeah, so in the obesity world, we think of microdosing as a dose below the lowest FDA-approved dose of a medication, such as a GLP-1. But there is a caveat. There is no consensus to this clinically right now in terms of an exact dose for a microdosing. And so there's more to be researched, really to be clear about the exact dosing of what would be a microdose.

• 2:23Flora Lichtman?

  Well, this is exactly what I want to get into. What kind of data do we have on the efficacy or safety of smaller doses of these GLP-1 drugs? Joey, I'll start with you.

• 2:35Speaker 05

  Yeah, well, I think it's really important that for these drugs to get approved by the FDA, these drugs have to go through Phase 1, Phase 2, Phase 3 studies, clinical trials, to get to a point where we test against placebo, right? So you imagine when you give somebody even a placebo and they're in a weight loss regimen for 12 weeks, like, they actually might lose weight, too, right? So it's important that we test against placebo to see, all right, did the drug do something? And so the lowest manufacturer doses are studied. It's when you then drop below that, there's not a lot of evidence in terms of like, what, there may be some case studies. And I really am hoping, you know, we can get groups to look at this.

• 3:17Speaker 05

  But the problem may be, you know, how do you finance a study like that? If a drug manufacturer doesn't want to do it, who's going to maybe fund that study to see if they are safe and effective? And like I said, I'm not as worried about safety as I am efficacy, probably, on the microdose side.

• 3:34Flora Lichtman?

  Jorge?

• 3:35Speaker 04

  Yeah, so, you know, I see patients that have done really well on low doses. And there is a potential for using microdosing. But as Joey said, there's not real data to support microdosing right now. And I agree with him. I think that research really could expand on this because I've had patients on the lowest dose of something like Tersepatide 2.5, and they've lost 50, 70 pounds on it. Their metabolic markers, A1C, cholesterol, glucose numbers, you name it, they get better. But we don't know exactly why this particular patient did so well on the lowest dose. And some patients on the highest dose do not respond to these medications at times.

• 4:18Speaker 04

  So it's really interesting and promising, but I think that there's still more data that needs to be available in order for us to make that recommendation.

• 4:28Flora Lichtman?

  Joey, well, you put a fine point on it. What is the challenge with financing studies on microdoses of GLP-1s?

• 4:35Speaker 05

  Right, so imagine, you know, you've invested hundreds of millions of dollars into the getting your drug approved and marketed in the United States. They likely did a wide range of doses in animals and in small human trials in the Phase 1, Phase 2. So Phase 1 and Phase 2 are typically where you work out dosing. So it likely has been done. And I'd assume if they thought they could use fewer milligrams and get same efficacy, you know, compared to placebo, right? So that's the other marker. You know, we'd be, okay, this is wonderful.

• 5:07Flora Lichtman?

  You know, we put out a call to listeners about their experiences with microdosing GLP-1s. And, you know, I have to tell you, we got a lot of calls and many of the stories, people had positive experiences. Here's one that kind of encapsulated what we heard.

• 5:21Speaker 06

  Yes, I have tried microdosing of the GLP-1. How did I get it? I got it from an online Teladoc company. And they send it, thinking that you'll do the doses they say. But that's not really a requirement. And usually, I just do small amounts. And I've had success with that.

• 5:46Flora Lichtman?

  So what struck me about this story is that this listener, you know, sort of becomes partly in charge of her own medical experience and her own dosing, because she's working with a, you know, a telehealth company. Jorge, what is your thought about this?

• 6:06Speaker 04

  Yeah, this is not uncommon, unfortunately. And I think a lot of this information is very important. One thing that we should talk about is the fact that a lot of microdosing is done with compounded medications. Compounded medications fall into this limbo of approvals. They don't go through the rigorous phase trials that Joey just alluded to. There was a shortage a couple of years ago, as you may recall, where we couldn't find any of these GLP-1s available for patients. And during that shortage, compounded pharmacies were able to develop compounded versions. And the way that I talk to patients about these medications is I give analogy, you know, it's almost like baking a croissant, right? You can have this recipe, but these compounded pharmacies

• 6:51Speaker 04

  have an almost recipe. They have close to, but it won't ever be a croissant, right? Like, it will be something very similar, but we don't know what impurities are in there. We won't know what other additives they might have. And so that's where trouble can strike. If we don't know how these compounded medications are affecting patients in a negative way. In this particular scenario, the patient did well. But I've had patients who have used compounded medications come to me after the fact. And they're like, why am I feeling so sick? And I can't give them an exact answer because the side effects that they're experiencing are much more severe than on the branded medications, or they're having very different side effects that are not commonly

• 7:34Speaker 04

  seen with the branded medications. And I think that that's why they go through these rigorous trials, so that we know, as a clinician, we know what the response is going to be, what the side effect is going to be. And so, yeah, so I think that in this particular scenario, follow-up is so important. And really being followed closely by your prescriber, whoever that is, either telehealth, in person. But going and coming back in a year is not ideal with these medications. It's actually, in my opinion, poor care.

• 8:09Flora Lichtman?

  We have to take a break. But when we come back, Joey, I want your take on this. And I want you to take us sort of inside compounding pharmacies and what they're used for and how they fit into this story. Stay with us.

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• 9:52Flora Lichtman?

  Joey, let's talk more about compounding pharmacies because I know this is what you study. What is their role in the medical ecosystem?

• 10:00Speaker 05

  Yeah, thank you. Compounding is part of our history as pharmacists. It's actually a beautiful part of the profession. I love compounding. It enables customization. Sometimes if a patient has an allergy to maybe an inactive component of a drug, the drug could be compounded. One of my favorite things when I used to be behind the counter was making a medication into a liquid for a patient who couldn't swallow a tablet, right? So like actually compounding is amazing for customization and really patient-level personalization. But what we've seen in the GLP-1 space is sort of a mass compounding, like that is sort of an oxymoron. We should not have a mass compounding. That is actually manufacturing.

• 10:43Speaker 05

  And that's where I get concerned is that we're not, it's not that we're trying to customize something special for a patient, is that we are trying to skirt around the manufactured products so we could maybe offer our own product. And that's the thing that's concerned me the most. I think we've got a lot of folks trying to do good in the supply chain, but I also think sometimes there's some bad actors too. And I think part of our job is to try to make sure we help protect patients. And so I don't blame the patient for seeking out these therapies. What I worry about are those who are marketing heavily to them, promising them all the benefits without the side effects. So how it gets marketed is really important. So compounders aren't subject to the same restrictions with

• 11:27Speaker 05

  marketing. Like when you see a drug ad from Eli Lilly or Novo, it's followed with all those side effects at the end, right? That's called fair balance. We don't see that with compounded marketing. And if you look at your Instagram or anything on social media, you'd be like, wow, this looks like it's curing everything and there's no downsides.

• 11:45Speaker 04

  Piggybacking on what Joey said, it's about access and cost, right? Like these medications cost a lot of money. And there has been a lot of conversations about the cost and how do we lower these costs, right? Hispanics and African Americans have the highest prevalence of obesity, the lowest use of these GLP-1s. And so I think that that's, that is important, right? Bringing costs. And so that's why compounding is popular. And the other reason is access, right? You have a quick call to this telehealth company and you can get an appointment. And with potentially, some are really good online health companies, some are not so rigorous in terms of figuring out, are they eligible

• 12:27Speaker 04

  for these medications? Do they have the BMI criteria? Do they have the medical conditions that could benefit from these medications? And I think just to add to the therapeutic efficacy of these medications, we don't know what dose of a microdose can potentially be beneficial or equivalent for the patient. And so we need more information, more data, more research on that topic, on all these topics, really.

• 12:55Flora Lichtman?

  Jorge, you know, at least in my feed, many of these microdosing GLP-1 ads feel like they're targeted to people who may not actually have a lot of weight to lose. Do we have data on the side effects of these drugs on people who don't meet the clinical criteria for obesity or diabetes?

• 13:14Speaker 04

  That's a great question. So, you know, all the studies had very clear criteria for inclusion of patients in these, participants in these studies. BMI greater than 27 with its associated obesity condition, BMI greater than 30 without any additional condition. So those two criteria are what we know. We do not know how the side effects would show up in other individuals. We don't know if they have a BMI less than this, how they will respond. We also don't know the efficacy of these medications for these individuals. So no, we don't have the data for these individuals that may not fit that criteria.

• 13:54Flora Lichtman?

  We got another listener call that touches on this idea about how the drug is compounded.

• 13:58Speaker 06

  So I, through my med spa, the place where I get my Botox and my filler and whatnot, they offered a compounded semaglutide. And it's also, they mixed it with a B12. And so basically in 12 weeks, I lost almost 30 pounds. And then I kind of like go on and off. But point is, it's really helped me maintain my weight and thus my confidence and all that sort of jazz.

• 14:29Flora Lichtman?

  So Joey, do we know if it's safe to take a GLP-1 that has other added ingredients, like B12?

• 14:37Speaker 05

  No, we don't know because it's not been studied. And that patient's experience, I totally believe. And I believe there's likely hundreds of thousands of patients who have benefited with a combined product. But I believe in our drug approval process. I believe in studying drugs. I mean, I tell my students that history doesn't repeat itself, but it often rhymes. And so over years and years, we've had instances where a slight modification is all it takes to like actually yield some rare side effect that we would have caught had we maybe studied it. A study we just completed, it's not just B12. We're seeing like multiple different B vitamins or combinations that are going with it. Part

• 15:19Speaker 05

  of this is because of the, if the manufactured product is available and there's no longer shortage, there's some question on whether or not the compounder can just make the same thing that the manufacturer sells, because that's actually not what a compounder should be doing. They should not be copying a manufactured product. So they would add B vitamins to it. B vitamins are typically innocuous. But there was a study that showed that under a chemical testing, when they're actually looking at the molecules, when you combine B12 with terzepatides specifically, a third little bump pops on the little graph that shows, wait, there's one other molecule that just popped in there. And that's how science works. And you combine two things, sometimes they interact and create a new

• 16:01Speaker 05

  entity. And so it's probably fine, right? But what if it's not? And so my thing is that we don't know. And so my plea is whether it's the manufacturers, the NIH, FDA, like somebody has got to like support the studies for this. So let's just study it, make sure that there's no weird side effect that could be happening that we're not paying attention to.

• 16:22Flora Lichtman?

  Yeah, let's find out before patients find out by doing experiments on themselves, right?

• 16:29Speaker 04

  Correct. And I get this question all the time about microdosing. It's all over social media. So patients ask, can I do microdosing? You know, and I explain to them, you know, my prerogative is safety. I can vouch for the safety of every single compounded medication out there because there is no process to double check that right now.

• 16:47Flora Lichtman?

  So you're a pharmacist, Joey, and Jorge made this analogy about that compounded pharmacies sort of don't have the original recipe. They're making their own version of the drugs. Is that how you'd put it? Like, is that always true? I guess there's probably a lot of people listening to this who are like, well, I have to get my drug compounded because I get a dose that's irregular, you know? And should they be skeptical of the drugs they're getting from compounded pharmacies?

• 17:15Speaker 05

  Right. So one thing to be clear, if it's a pharmacy that's licensed in the United States, that they do have a license and they are subject to a board of pharmacy at the state level. So sometimes you'll hear compounding pharmacies are like not regulated. Well, maybe they're not regulated by the FDA at the federal level, but they're regulated at the state level. And if the compounding pharmacy is doing everything above board, it should be low risk, you know? There's 4 billion prescriptions dispensed every year in this country and our supply chain is generally safe. And so I think it's really just what are the quality checks? When you're searching for a product or you've gone through a telehealth company, one of the challenges I had is finding out who the pharmacy was. So that's something that's a little troubling with some of the telehealth companies because

• 17:58Speaker 05

  they do not own the pharmacy, they're contracting it out. And I've talked to some patients that they would use a telehealth company, one month they get the dose and it comes in like a 1 milliliter syringe, and then the next month it's a 5 ml syringe. Well, for a patient trying to pull up a 0.5 ml dose, you would want a 1 ml syringe, not a 5 ml syringe, right? So like, there are just little things like that. But the customer sees one company, they're logged into one app. They don't know that they're actually contracting to three, four different pharmacies across the US.

• 18:30Flora Lichtman?

  Any last thoughts you want to leave our listeners with?

• 18:33Speaker 04

  Well, I think it's so important that whoever is prescribing your medication gives you a follow-up plan. Who will I call if I have a problem? Who will I call if this is not working? And ask questions before you start taking the medication. And always reach out to them if there is a problem or reach out to your regular provider, because I think that that's going to be helpful to prevent any potential consequences, side effects and things like that.

• 19:02Speaker 05

  Yeah. And I would just say for patients, as you're, if you're going through this journey, having a regular provider that sees you that isn't maybe also selling you the drug is probably a good thing in terms of like, you know, if they don't have a vested interest in you taking the product, that's probably a good thing. And don't be ashamed. If you got a compounded product from a telehealth company, that's okay. Tell your doctor. Because I've talked to some patients that they don't want to tell their doctor that they're on. I'm like, please, no, tell your doctor.

• 19:28Speaker 04

  Yes, yes. Agreed.

• 19:32Flora Lichtman?

  Thank you both for joining me today.

• 19:34Speaker 04

  Thank you so much for having us.

• 19:36Speaker 05

  Thank you.

• 19:36Flora Lichtman?

  Dr. Jorge Moreno, obesity medicine physician and assistant professor at the Yale University School of Medicine, and Dr. Joey Mattingly, a pharmacist and associate professor of pharmacotherapy at the University of Utah. This episode was produced by Shoshana Buxbaum. I want to thank all our listeners who called in with their story. You really helped us understand this landscape better. So thank you. And if you have questions or comments, you can always call. 8774 sci-fi is our number. Thanks for listening. I'm Flor Lixman.