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All right, all right, all right. Now that I set it up enough, we'll be right back. We're just trying to fulfill our life calling and our mission. This is Dr. Choppa's OBGYN no Spin podcast Podcast family. In my renewed commitment to tell you what you need to know quickly and then move on, let me just give you the facts here of what these two independent systematic reviews found, and then we'll be done. Right, but this way you can educate your patients when they come back super nervous because they had a conception, maybe, you know, not so well timed, and they've been on this medication without a washout. Now, the first systematic review, which was in March of 2026, looked at two different classes of meds, GLP1s by themselves. Remember, that's glucagon, like peptide 1 receptor agonists. So GLP1s as well as the combination of GLP1 plus GIPS. Remember that GIPS is glucose insulinotropic peptide. And when you combine that with a GLP1 it, it actually gives much better weight loss and more sustained over time. Okay, so that is tirzepatide. As a combination tirzepatide, it works two different ways. Okay, so the systematic review from March looks at both types of medications, GLP1s by themselves, like the Ozempic wegovy family, and then dual GLP1 GIP receptors, which is like Tirzepatide. The one From April of 2026 only looked at GLP1. So let me read you each title in March of 2026 out of diabetes, obesity and Metabolism. The title of this systematic review is safety of GLP1 and dual GOP1 GIP receptor agonists. Told you in Preconception, Pregnancy and Lactation A Systematic Review of Maternal, Fetal and Neonatal Outcomes. Man, that's a big title. The one from April of 2026 is just looking at GLP1s. The title is Neonatal and Obstetric Outcomes following Periconception Exposure to glucagon. Like peptide 1 receptor agonist. A Systematic Review and meta analysis. Short of it is the one in April looks at two classes of medications both based on GLP1 and then the one from April looks only at GLP1s. So yes, there's a potential for concern here because in embryonic development that type of peptide, glp. Right, Glucagon, like peptide actually is in a lot of different organ systems during organogenesis, including mainly the GI tract obviously and the pancreas as well as other things. And in preclinical studies where these little, you know, lab rats were given multi dose injections or whatever, however they were given this medication in levels that were above what is humanly allowable. So just remember that it caused some issues. Okay, so in preclinical studies for these medications, yeah, they're like, oh, that's teratogenic, there was bad ossification centers that some skeletal malformations, they had growth restriction. So there is true cause for concern. Remember that preclinical is to mimic kind of like the worst environment that you could possibly do and doesn't always translate to human studies. So that's the good news. So I think I've kind of spilled the beans there a little bit. That's much more reassuring. What is found in human studies, we're going to get into these systematic reviews here in a minute. Than what's found in preclinical. But if the question is is GLP1, are those receptors and those molecules active during the embryogenic time frame? The answer is no question. Absolutely. Now one of the big confounders when you're looking at GLP1s and periconception malformations has to do with the overall condition of the patient. Remember, they're on this medication because they've got diabetes or they're obese, which is a chronic oxidative state, which raises your cortisol. There's other Issues that go with that, like hypertension, potentially some medications that are used for antihypertensives. Do you all get what I'm saying? So it's not just a GLP one is that that actually compounds the situation of why they're on that, which is the fact that obesity in and of itself because of some micronutritional deficiencies, has a higher risk of malformations Anyway. Okay, so all that has to be taken into account. But this is why these two systematic reviews and meta analyses are very helpful now, even though there's one from March and there's one from April of 2026. Guys, these aren't the only ones. And I think we've kind of touched on this in the past as well, because last year in 2025 was the Parker data. Parker et al took a look at GLP1 receptor agonist safety data through the clinical trials. Right. So when a medication is approved, it goes through, you know, their phases and then it goes through market surveillance to make sure that there's no other signals that maybe were missed in the preclinical or were seen in preclinical that are being reproduced in true circulation and then halted. Right. So Parker took a look at that regulatory clinical trial data in 2025 and published that review. So this is nothing new. And in that review he said, you know what, this is pretty reassuring. The incidence of congenital abnormalities was relatively low, and those pregnancies didn't really have a big bump or a big rise or a glip in any kind of single organ clustering effects. So like, I don't know, this seems to be okay. However, you know, there was again these big confounders like, well, when did the medication stop before pregnancy? Were there other health conditions related? But it was very reassuring. That's the Parker data of the review of regulatory trials in 2025 that came out in obesity, diabetes and metabolism. So we already had some reassurance that let's not, let's not, you know, endorse this, using this medication and then getting pregnant. Definitely not using this medication throughout pregnancy. Although I know we covered this in the past episode. There are case reports, guys, where patients have used this for like horrible diabetes. They just don't, can't, can't get control of this thing. They're like, hey, trials, GLP1. We know you're pregnant, but we got to do something. And it actually worked. It helped control that. But those are very, those are off label. Those are very, very, you know, protocol regimended. And there's nothing that is done in large clinical trials. So I am not advocating for that to continue in pregnancy, although people have published that and I'm talking about a handful of reports where GOP1s were on purpose continued throughout pregnancy. Okay, so even though this is covered in 2025, let me just very quickly tell you the data here from these studies and then we'll call it a day. Let's start first, I guess with the March study. This is the one that looked at the dual medications and thankfully, very reassuringly, it was okay. Again, not not wanting patients to do this, but if you find a patient who becomes pregnant while on this medication, this can be very helpful. So this first publication out of Diabetes, Obesity and Metabolism was a systematic review, not a meta analysis. But let me read you the conclusion and we're going to work through this. Quote, current evidence suggests that preconception or early pregnancy exposure to GLP1 based therapies is not, let me say that again, is not consistently associated with increased maternal, fetal or neonatal risk, although data on continued use throughout pregnancy remain limited. So there it is right there. We don't want anybody to continue this in pregnancy. Pregnancy is not time to caloric restrictions. Pregnancy is not a time to lose weight. I mean that you're going the opposite direction here, for heaven's sakes. Even women who are obese, there's still a certain weight gain that they must do to account for the very issues of pregnancy. Right? It's got to be at least 15 pounds because that is the extra blood volume, that's the weight of the placenta, amniotic fluid, you know, six to seven pounds ish is the child itself. The breasts gain some weight because of fluid retention as well. So when you add up all that, it's at least, you know, 12 to 15 pounds. So even in the obese patient, they gotta gain something. Okay, so this was a systematic review looking at the data and they included 36 studies that ended up meeting their inclusion criteria. It's not bad. So 36 studies were included. And based on this review, there was no single signal that said, whoa, whoa, whoa, this is, this is kind of harmful. Now let me tell you also where the data is very limited. Lactation, okay? So we just don't know. It's just better just to hold off. Plus breastfeeding is a great way to lose weight because you're burning extra calories, although you got to maintain adequate nutrition and hydration to keep the lactation process going. So According to this March 2026 publication, quote, Lactation data is sparse. One pharmacokinetic study reported no detectable somatoglutide transfer into human milk. End quote. That's good. Super reassuring. But I'm not necessarily gonna recommend that a patient is on these while breastfeeding. It seems to be no issue at all. It seems to be just fine. But until we have better data, I'm not gonna mess with that when there's potential real concerns here for the child that we just don't have, especially long term. Okay, so we've got 2025 from the regulatory trial saying I don't really see anything here. It seems to be okay though. We're not advocating contin this. We have March of 2026 again. Seems to be okay. Now let's come to April 28, 2026 in the gray journal. Remember, this is a systematic review and a meta analysis, which means that they looked at the data independently. Again. Now, unlike the one that we just talked about, this included 22 studies. Okay, so the first one was a little bit more. It was 36 studies. This one from April is 22 studies. But thankfully, outside of a minor little glip in the kidneys. I'm gonna talk about this in a minute. And it was very, listen to the word minor, very minor little blip in the findings on renal malformations. It seems to be okay. The big limitation here in this meta analysis is man, the data was everywhere. Okay, so there was a lot of heterogenicity here that can throw off some of the data. Heterogeneity because patients took this for a variety of different reasons. Which again goes back to their core condition, which may affect periconception outcomes. Anyway, but in short, quote, current human evidence does not demonstrate a consistent association between periconceptional glucagon, like peptide 1 receptor agonist exposure and major adverse fetal, pregnancy, obstetric or labor outcomes, end quote. So let's stop there. That's good news, guys. From April 2026, systematic review and meta analysis, GLP1s around pregnancy. And you can relax. It seems to be okay. The kid probably is not going to come out with three heads. However, the minor little blimp, it was very small. Let me read it directly because I don't want to misrepresent this quote. A small but statistically significant association with renal malformations was detected. Now gasp. Right. But wait, before, before we freak out. The odds ratio was 1. Okay, so it's still in that one zone with 95% confidence interval of 1.09 to 1.39. So yes, it bumped up. We don't want it to bump up. But it's very minor. And as the authors say, after their evaluation of this data point, quote, however, this was largely driven. Here it is, guys. By a single large cohort with substantial baseline imbalances, end quote. In other words, you gotta take a look at all of the other factors that that patient cohort had. Okay? So if patient asks you anything, anything that you should look out for. Well, maybe. I mean, there's a little blimp in one review on renal issues, but the data was very confounded by a lot of other things. And it was a very minor change, if that was even real. But the overall conclusion was that there was no conclusive evidence that a consistent association between exposure of these medications and something wrong with the child or even in terms of your lab outcome is going to be an issue. That's good news. The authors go on to say, quote, the observed risk for renal malformation should be interpreted with caution. There it is again. As it likely reflects residual confounding by maternal disease severity, end quote. Man, I hate it when I'm right. I mean, see what I'm saying, guys? That's the thing. So if your patient had a BMI of 50 and was taking these meds and she dropped down to 40 and that triggered ovulation and the big deal, the big confounder there. I don't mean big like in a bad way. I mean the large confounder there. Well, I don't mean large in a negative way there either. How about the biggest factor is the person's weight, because obesity does have a chance of higher malformations because of oxidative stress and everything else we talked about. Okay? The good news is, quote, these findings provide cautious reassurance regarding inadvertent exposure. So remember, these are inadvertent. Not. We don't want to do this on purpose. Inadvertent exposure and does not support routine. I'm sorry, but does not support routine use during pregnancy, end quote. So even though we don't find anything wrong, it doesn't mean that you can say, honey, knock yourself out. Go be like Serena Williams. Give yourself them injections all through 36 weeks. No one is advocating for that now. Medicine moves fast. Maybe this would be a new way to treat GDM. It's not going to be, but who knows? Hey, 10 years from now, we thought some wax stuff wasn't going to happen, and it did. So as of right now, There is no GLP1 or GIP medication that is approved for continuation in pregnancy. It's not approved in the first part of pregnancy, but if there's inadvertent exposure, it seems to be okay. Podcast Family Very quickly, we've taken a look at three studies, the Parker 2025 from the clinical trials and then two that have looked at overall population data. One was in March of 2026, the other was in April 2026. And I told you, my new commitment is to tell you what you need to know quickly and then be done. So if you're counseling the patient on this, especially if you're starting them, remember, talk to them about birth control. But if they get pregnant on this, despite the fact that they did not have a washout, it's going to be okay. They still would need rate of growth ultrasounds because the preclinical studies showed some potential for growth restrictions. So that's a good idea. And of course, they need a detailed anatomical survey, as all patients do at 18 to 22 weeks. But there's nothing here that says that they need specifically like a cardiac echo or specific, you know, fetal MRI. They don't need anything like that. Just a routine 18 to 22 level two ultrasound without an echo. That should be just fine. Podcast family as always, we're thankful for you. We're glad that you're part of our podcast community. And now that we've done all that, Michael, let's take it home.
