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Three studies, two directions, one average

Pooled, GLP-1 exposure showed no association with hypertensive disorders of pregnancy. Two of the three studies found lower risk and one found higher.

Glenn Torres5 min read
Pooled across three studies0.910.571.471.0two studies found lower risk · one found higherThe average is not a resolution of that

Preeclampsia and the other hypertensive disorders of pregnancy are among the things obesity makes more likely, so a drug that treats obesity might plausibly reduce them. Three studies have looked. They do not agree, and the thing that gets quoted is their average — a different outcome from the ones the pregnancy safety review covers.

What exists

Five databases searched from inception to December 2025 turned up 75 records, of which three retrospective cohort studies qualified. [1] All three were conducted in the United States between 2014 and 2025, and between them they covered 10,880 pregnancies: 4,942 exposed to a GLP-1 around conception or in the first trimester, and 5,938 not.

The exposure pooled seven different drugs — semaglutide, liraglutide, dulaglutide, tirzepatide, exenatide, lixisenatide and albiglutide. That is a class exposure rather than a drug exposure, and the class does not behave uniformly on other outcomes.

The disagreement, and the average

Two of the three studies found lower rates of hypertensive disorders among exposed pregnancies. The third found higher. Pooled with a random-effects model, the odds ratio came to 0.91 with a 95% CI of 0.57 to 1.47.

Reading the interval

0.57 to 1.47. At the lower end, a 43% reduction in hypertensive disorders of pregnancy — a large and clinically important benefit. At the upper end, a 47% increase, which would be a serious harm. The evidence cannot distinguish between those two worlds.

“Not significantly associated” is the correct technical summary and the most misleading available phrase, because it reads as a statement about the drug when it is a statement about the evidence — the same distinction that separates a null from a demonstration of equivalence.

What it would take to know

The authors call for large prospective studies, which is the right request and a slow one. Randomized trials will not happen here — nobody will randomize pregnant women to a drug that is not recommended in pregnancy — so the realistic path is much larger observational cohorts with better exposure data.

Until then, hypertensive disorders sit in the same category as most pregnancy questions about these drugs: not shown to be raised, not shown to be lowered, and studied in far fewer people than the number currently taking them. Pooling more of that evidence will narrow the interval without fixing what pooling cannot fix.

The practical version

Anybody who could become pregnant while taking one of these drugs should be discussing it before starting, not after a positive test. The evidence on every pregnancy outcome is thinner than the number of people exposed would suggest, and an intake form is not where that conversation belongs — the questions sellers leave to you include most of the ones that matter here.

Frequently asked

Do these drugs raise or lower the risk of preeclampsia?
Nobody knows. The pooled odds ratio was 0.91 with an interval from 0.57 to 1.47, which contains a large reduction and a large increase.
Why did the studies disagree?
The review does not establish why. Two found lower risk among exposed pregnancies and one found higher, and with three studies the statistics that measure disagreement are barely computable.
Does 'no significant association' mean it is safe?
No. It means the available evidence cannot distinguish a benefit from a harm on this outcome. That is a statement about the evidence rather than about the drug.
Will randomized trials settle it?
Not on this question. Nobody will randomize pregnant women to a drug that is not recommended in pregnancy, so the realistic path is much larger observational cohorts.

Sources

  1. [1] Pisani D, et al. (2026). Hypertensive disorders of pregnancy and GLP-1 receptor agonist timing: a systematic review and meta-analysis Endocrine. PMID 42536323

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