Subject: GLP-1 Pregnancy Fears vs Reality… The First Real Data Is In
From: Dave Knapp from On The Pen <[email-masked]>
To: [email-masked]
Date: Sat, 28 Mar 2026 17:38:29 +0000
List-Id: <onthepen.substack.com>

View this post on the web at https://onthepen.substack.com/p/glp-1-pregnancy-fears-vs-reality

If you’re currently on a GLP-1, or if you’ve been on one long enough to feel your body experience massive changes, you already understand why this conversation matters. These are not casual medications for this community, they are often the first thing that actually moved the needle after years of trying everything else. For many others, it was the first real hope offered, after the promises of metabolic surgeries failed to deliver as promised.
That is exactly why pregnancy can add such a complex layer to the journey, because the same medication that helped restore metabolic health is also restoring ovulation in ways many women using GLP-1 therapies did not necessarily expect. For many in this community, pregnancy is no longer some far fetched possibility. Once those systems start functioning again, pregnancy becomes something that can happen much faster than the timeline you may have had in your head.
A new systematic review pulled together 36 human studies (over 2,000,000 patients) looking at exposure to GLP-1 receptor agonists and dual incretin therapies like tirzepatide across preconception, early pregnancy, and postpartum. Most of the data comes from observational cohorts, so this is real world experience being analyzed, not tightly controlled clinical trials designed to answer one narrow question.
Across those cohorts, early exposure, especially around conception and during the first trimester, was not consistently associated with increased risk of major congenital malformations. When researchers adjusted for underlying metabolic disease, outcomes like stillbirth, neonatal mortality, and fetal growth restriction also did not show a reproducible increase compared to similar patients treated with insulin or other therapies.
That does not suddenly make this issue simple or risk free, and it is certainly not being presented that way in the literature. What it does do is start to chip away at the idea that early exposure automatically equals worst case scenario, which is the exact question many patients and prescribers have quietly had in the back of their mind.
Maternal outcomes were far less clean, and that part of the data feels exactly like you would expect at this stage. Rates of gestational diabetes, hypertensive disorders, preterm birth, and gestational weight gain were all over the place depending on the study, with no single direction that clearly stands out.
Where this really lands for the OTP community is with Polycystic Ovary Syndrome, and this is not some small corner of the audience. This is a huge group of women who have spent years being told their condition was secondary to weight instead of something with its own biology and its own set of levers. In the review, GLP-1 therapies were associated with improvements in both metabolic and reproductive markers in women with PCOS, including signals around insulin resistance, hormonal balance, and in some studies, changes in menstrual regularity and ovulation. These were often secondary outcomes rather than primary endpoints, but the pattern showing up across studies is consistent enough that it is getting harder to ignore.
That is exactly where the data starts to line up with what this community has already been seeing in real life. There are countless stories of cycle regulation, improved ovulation, and in many cases unexpected pregnancies after starting therapies like semaglutide or tirzepatide, and those stories have been piling up long before the data showed up on the scene.
What is happening now is not that science suddenly discovered something new, it is that it is finally starting to measure what patients have been reporting for years. That shift from anecdote to early structured evidence is slow, but it is meaningful when you start to see the same signals show up in both places. 
You can see that shift even more clearly in how new trials are being designed. The PERIODS trial out of Germany is looking at tirzepatide specifically for ovarian dysfunction, with ovulation frequency and menstrual regularity as primary endpoints over a 72 week period, which is a very different question than most prior studies have asked.
That matters because endpoints are how the system decides what a drug actually does, and PCOS has historically been studied through indirect markers that never fully captured the condition itself. When ovulation becomes the outcome, the framing starts to move closer to what patients have been describing all along.
Lactation is still largely an unknown, which is not surprising given how early this entire space is. There is one small pharmacokinetic study involving Semaglutide [ chatgpt://generic-entity?number=3 ] that did not detect transfer into breast milk, but the patient pool was small, and more studies will likely be necessary for many clinicians to feel comfortable giving GLP-1 use during lactation the “thumbs up”.
The biggest gap across all of this is duration, and that is where the uncertainty really shows up. Most of what we have looks at early exposure, not what happens if someone stays on therapy throughout pregnancy, which leaves the most obvious question is still sitting there unanswered.
So what you are left with is not clarity, but context, and for this community that actually matters. Instead of operating in a complete vacuum, there is now at least some human data suggesting that early exposure is not consistently tied to the outcomes people fear most, even though the full picture is still being built.
And that is really the point of this moment. The science is not finished, but it is no longer silent either, and for a community that has been living this in real time, that shift feels long overdue.
I’m not a doctor, and this is not medical advice. I’m sharing what the data is starting to show and how it connects to what this community is experiencing. ALWAYS talk to your doctor about your own situation.

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