Cannabis Exposure During Pregnancy; Tirzepatide Cessation and Weight Gain

Derick Alison
Derick Alison
17 Min Read

TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week.

This week’s topics include metformin plus insulin in type 2 diabetes in pregnancy, newer vaccine technologies in adults, cannabis exposure during pregnancy, and tirzepatide (Zepbound) cessation and weight gain.

Program notes:

0:40 Two studies on vaccines in adults

1:40 Recombinant flu vaccine

2:40 Protects other populations

3:24 mRNA vaccine against RSV

4:24 One more vaccine against this virus

5:04 Cannabis exposure during pregnancy

6:04 2/3 had ongoing exposure

7:04 Why use during pregnancy?

7:35 Addition of metformin to insulin in pregnancy

8:35 Halted at 75% accrual

9:35 Issue of type 2 diabetes increasing

9:55 Tirzepatide cessation and weight

10:55 Those who continued lost more weight

11:52 Not long lasting

12:23 End

Transcript:

Elizabeth: A couple of newer vaccine technologies and their utility in adults.

Rick: Maintenance of obesity-reducing medications.

Elizabeth: If we add metformin to insulin in pregnant persons with diabetes, does that help outcomes?

Rick: And does cannabis exposure adversely affect pregnancy outcomes?

Elizabeth: That’s what we’re talking about this week on TTHealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore-based medical journalist.

Rick: And I’m Rick Lange, president of Texas Tech University Health Sciences Center in El Paso, where I’m also Dean of the Paul L. Foster School of Medicine.

Elizabeth: Rick, we’re going to turn first to the New England Journal of Medicine. There are two studies published this week taking a look at two different vaccines in adult populations. I have chosen to treat these two together because they employ newer technologies to raise these newer vaccines. They both have proved to be fairly efficacious. I’m going to talk first about the recombinant or standard-dose influenza vaccine in adults under 65 years of age.

What we know about the flu vaccine — the one that’s raised in eggs, this old fashioned technology — is that it is susceptible to what’s called antigenic drift during the manufacturing period. It takes a long time to get that thing ready and by the time we get it here, sometimes there is really a substantial mismatch between the circulating strain and the strain that was used for the vaccine development.

So we do have this other thing, this high-dose, recombinant influenza vaccine. Right now, we administer that to folks who are 65 years of age and older. They wanted to take a look at this in adults aged 50 to 64 years and in those 18 to 49 years of age. They either got one of two standard dose influenza vaccines and they looked at this during the 2018 to 2019 period and 2019 and 2020. Their primary outcome was influenza A or B that was confirmed by PCR.

A huge database here, 1,600,000+ people who received the vaccine between those ages 18 and 64, 600,000+ in the recombinant vaccine group, and almost a million in the standard dose. What they basically found was that it actually was helpful. The recombinant vaccine was not significantly more protective against hospitalization. However, it did have a protection — it offered protection of about 15% against infection.

The authors say that this is fairly modest. However, I want to point out that the other populations who are susceptible to the flu, that’s older people, this is an important place where if we reduce the infections that they get, we’re also going to reduce it for other folks. I want to hear your comments about that before we turn to the second one.

Rick: I totally agree. The current vaccine we have, because of the antigenic drift, is only about 40% to 60% effective, so an additional 15% is helpful. It’s both a manufactured vaccine — which makes it less likely to drift away from the influenza we’re seeing — and it’s also three times the amount of protein as well. By the way, no safety issues at all. This seems like a better alternative — especially for people that are allergic to eggs and can’t receive the current vaccine. This is good news.

Elizabeth: I think it is good news and let’s turn to the other, which is an mRNA-based vaccine against respiratory syncytial virus or RSV, an important pathogen impacting older adults and [it] actually results in significant hospitalizations and deaths. Unfortunately, I would just note that yesterday the CDC reported data saying that our currently available RSV vaccine has only been received by about 15%, nationally, of those adults who are eligible for it.

This is a study that reports results on this mRNA-based vaccine. 35,000+ participants. Hey, what happened? Did you get either upper respiratory or a lower respiratory tract disease after you got vaccinated? Sure enough, they found that this single dose of this, there were no evident safety concerns. There was a lower incidence of lower respiratory tract disease and acute respiratory disease compared with placebo in adults 60 years of age or older who received it. One more part of the armamentarium against RSV and I would just say to anybody who is that age, it’s time to get the vaccine folks.

Rick: Elizabeth, I’m glad you mentioned that because the annual incidence of RSV infection among adults, especially older adults, is about 3% to 10%. For example, in 2019 there were 5.2 million cases of RSV among adults. It led to 470,000 hospitalizations and here is the key point: 33,000 in-hospital deaths among adults 60 years or older. If our listeners are adults, especially older adults, and they haven’t been vaccinated for RSV, I think it’s incredibly important.

Elizabeth: Me too. Which of yours would you like to turn to?

Rick: Let’s talk about cannabis exposure during pregnancy. This is a multicenter observational study. This study was done in pregnant women at eight U.S. medical centers and they had stored urine samples. These women were studied from 2010 through 2013 and the project was just completed this past year. They were able to examine the urine to say which women had had cannabis exposure during pregnancy and whether it was the first trimester or afterwards, and whether it adversely affected the pregnancy outcomes.

When they studied this in monkeys, it looked like cannabis exposure actually resulted in alterations of the placenta — less oxygenation, decreased perfusion and that can affect fetal outcome. The fetal outcomes that it can affect are preterm birth or stillbirth, hypertensive disorders of pregnancy, and small-for-gestational-age birth.

When they have looked at over 9200 women, about 6.6% had had cannabis use. A third of those were only in the first trimester and two-thirds of those had ongoing exposure after the first trimester. Women that had no cannabis use, those outcomes I mentioned occurred in about 17%. But in women that had cannabis exposure, it was 26%, almost 30% higher. It was cannabis use after the first trimester, and there happened to be a dose-response curve. The higher that dose of cannabis or the higher the exposure, the more likely these adverse outcomes.

Elizabeth: Very concerning, of course, now that it is legalized all over the country — so many people are using it. In fact, I was recently in a place where vaping cannabis is allowed on the street and I felt like I was going to have an exposure to it whether I wanted it or not.

Rick: Oftentimes, we think well, gosh, since the baby is forming in the first trimester that I’ll avoid anything that could potentially harm the baby’s development, and after that it shouldn’t be an issue. But in fact, cannabis use following he first trimester was the thing that seemed to be associated more with these adverse outcomes.

Elizabeth: I guess one thing I’m wondering is why women would be using it during pregnancy. As you know, it’s touted a lot for things like chronic pain. I’m just wondering if there is any data on that.

Rick: This particular study just associated the presence of cannabis in the urine sample and the outcome. It didn’t examine why the mothers used it. I really can’t answer that.

Elizabeth: It sounds like, though, it would probably be a good idea to give it a miss.

Rick: Yep. Even if it is used to either decrease pain or for antiemetic, anti-nausea properties, there are other things we know that are safe and don’t have these adverse outcomes.

Elizabeth: Staying in JAMA then and also looking at pregnant women, this study is looking at the addition of metformin to insulin in women 18 to 45 years of age with preexisting type 2 diabetes or diabetes diagnosed prior to 23 weeks of gestation. Clearly, the question was, “If we add metformin to their existing insulin regimen, can we look at these primary outcomes, the composite of perinatal death, preterm birth, large or small for gestational age, and hyperbilirubinemia requiring phototherapy for the infant?”

They looked at 794 women, almost 400 in each arm. They also had a very wide range of ethnicities. They found that this composite adverse neonatal outcome occurred in 71% of the metformin group and 74% of the placebo group. The study was halted at 75% accrual because of futility and detecting a significant difference. They did find that metformin did seem to reduce the large-for-gestational-age. They say that that could use some follow-up to see if it’s borne out in larger studies, but at the moment it appears rather disappointing, this strategy.

Rick: We have talked before about gestational diabetes and type 2 diabetes becoming more prevalent in this age group and among pregnant women. The main treatment is to reduce the glucose level. We know that insulin does that. It is associated with some weight gain, but it’s fairly effective. It would have been nice if metformin in women with type 2 diabetes was more helpful, but it appears that it’s really not.

It didn’t cause more hypoglycemia, but it really didn’t produce the outcome we were hoping for. You don’t usually report on a negative study, but it’s important in this particular case, and it really urges us to look for other treatments that may be more effective either to use with insulin or in place of insulin.

Elizabeth: The editorialist notes that, of course, this issue of gestational diabetes and frank type 2 diabetes before pregnancy is increasing at an alarming rate, largely due to obesity. Once again, taking a look at that — and that segues us very well into what you’re going to talk about next — what do we do about our obesity problem?

Rick: We’re going to talk about one of the medications, tirzepatide, which is a weight-reduction medication. It’s a GLP-1 receptor agonist. These are synergistic effects that reduce appetite, should reduce food intake and change the metabolic function. We know it’s effective in weight reduction because we’ve done it in short-term studies. What we haven’t done, though, is look to see if we maintain that for a long period of time, do we have continued weight loss or is there weight gain? What happens if you start it and then you stop it?

That’s exactly what this study did. We looked at continued treatment with either tirzepatide or placebo in individuals that have already been on tirzepatide for 36 weeks and then were transferred over to either continue tirzepatide or to placebo. By the way, this is a once-weekly subcutaneous injection.

Seventy sites and four countries on tirzepatide. Those individuals that received it, there was about a 21% weight reduction over that time period. Then they randomized them to either continue it or stop it. For those that continued it, there was an additional 5.5% weight reduction. Those that stopped it, unfortunately, they experienced a 14% weight regain. For those that continued it, their blood pressure was down, their hemoglobin A1C was down, and their cholesterol was down. A cautionary note to our listeners who think that this is the answer — now, what we don’t know is, what are the long-term side effects?

Elizabeth: Now, this is rather disappointing and also concerning, isn’t it? Because these medications are expensive and, as you suggested, it’s unclear exactly what’s going to happen if people stay on them for years. It calls into question for me, what exactly is the mechanism by which these medications result in weight loss? My understanding is that it really just completely eliminates someone’s appetite and sometimes results also in nausea, so that they really are twice sort of reluctant to eat.

Rick: In fact, that’s the major side effect from this particular medication, but it’s not long-lasting. That indicates that obesity ends up being a chronic disease and like most chronic diseases, we’re much better off preventing them than treating them.

Elizabeth: Yes, indeed. On that note then, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.

Rick: And I’m Rick Lange. Y’all listen up and make healthy choices.

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