Preconception incretin therapy reduces pregnancy and cardiometabolic outcomes in polycystic ovary syndrome
- Design
- Retrospective cohort · 96252 participants · Hard outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationINDIRECT: women aged 18 or older with PCOS/PMOS, which the authors describe as a metabolic-endocrine syndrome the target group does not have; BMI, diabetes status and age distribution are not reported.
- Could weight loss explain it?
- PossiblyPossibly: no weight or glycaemic change is reported, and the authors frame the result as pre-conception metabolic optimisation; matching on baseline anthropometrics addresses confounding, not mediation.
- Study tier
- Study tier 3LOW: a single observational target trial emulation in health-record data, capped at LOW.
- Assessment
- Version 3 · Two reviewers differed; settled by a recorded ruling · Oct 19, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
Using a large health-record network, this study compared women aged 18 or older with polycystic ovary syndrome who took liraglutide, semaglutide or tirzepatide before conception with matched women taking metformin, 48,126 per group. GLP-1 drug use was linked to a lower risk of a combined measure of pregnancy complications (HR 0.38), and in exploratory analyses to lower risks of major cardiovascular events and type 2 diabetes, though results varied in some sensitivity analyses. This is an observational association, not proof of cause, and it says nothing about using these drugs during pregnancy.
01Findings
What the study reported
- Drugs
- Liraglutide, Semaglutide, Tirzepatide
- Comparator
- metformin
- Primary outcome
- Composite of adverse pregnancy outcomes over two years
- Effect
- Composite adverse pregnancy outcome HR 0.38; exploratory MACE HR 0.88 and type 2 diabetes HR 0.31; associations varied across some sensitivity analyses
- 95% confidence interval
- 95% CI 0.34-0.41
- Follow-up
- over two years
- Adverse events
- not reported in abstract
- Limitations
- Observational target-trial emulation in health-record data, open to residual confounding; associations varied across sensitivity analyses and the study cannot assess safety or efficacy during pregnancy.
Who was studied
- Age min
- 18
- Sex distribution
- women only
- Obesity status
- not reported in abstract
- Diabetes status
- not reported in abstract
- Cvd status
- not reported in abstract
- Ckd status
- not reported in abstract
- Baseline condition
- polycystic ovary syndrome (PCOS/PMOS)
- Sample size
- 96252
- Inclusion exclusion
- women ≥18 with PCOS/PMOS on pre-conception GLP-1/GIP RA or metformin; 1:1 propensity matching
Study quality details
- Study design
- Retrospective cohort
- Sample size
- 96252
- Randomization
- no
- Blinding
- n/a
- Comparator
- metformin
- Follow up duration
- over two years
- Outcome type
- hard
- Replication
- not assessed
- Consistency with other evidence
- not assessed
- Population applicability
- INDIRECT
- Statistical precision
- 95% CIs reported; event counts not reported in abstract; 48,126 patients per group after matching
- Risk of bias
- not assessed
- Funding conflicts
- unclear
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- not reported in abstract
- Industry funded
- Unclear
- Manufacturer
- not stated in source
- Sponsor role
- not reported in abstract
- Author conflicts
- not reported in abstract
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[BACKGROUND] Polycystic ovary syndrome (PCOS), now polyendocrine metabolic ovarian syndrome (PMOS), is associated with reproductive and cardiometabolic complications. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) receptor agonists (RAs) improve obesity-related outcomes, but their impact on pregnancy outcomes in PMOS remains unclear. [METHODS] We conducted a target trial emulation using the TriNetX global federated health research network. Women ≥18 years with PCOS/PMOS receiving pre-conception GLP-1/dual GLP-1/GIP RA therapy (liraglutide, semaglutide or tirzepatide) were compared with metformin. Propensity score matching (1:1) accounted for demographics, anthropometrics, comorbidities and medications. The primary outcome was a composite of adverse pregnancy outcomes (hypertensive, glycaemic, placental, delivery, labour, foetal growth, preterm and early pregnancy complications) over two years. Individual pregnancy endpoints, major adverse cardiovascular events (MACE) and type 2 diabetes (T2D) were exploratory secondary outcomes. Cox regression generated hazard ratios (HRs) and 95% confidence intervals (CIs). [RESULTS] After matching, 48,126 patients were included per group. Pre-conception GLP-1/GIP RA use was associated with lower risk of the composite pregnancy outcome (HR 0.38; 95% CI 0.34-0.41). Exploratory analyses also demonstrated lower risks of individual pregnancy endpoints, MACE (HR 0.88; 95% CI 0.81-0.95) and T2D (HR 0.31; 95% CI 0.30-0.33). Associations varied across some sensitivity analyses. [CONCLUSION] Pre-conception GLP-1/GIP RA use in women with PCOS/PMOS was associated with lower risks of adverse pregnancy outcomes and cardiometabolic disease compared with metformin, consistent with potential benefits of pre-conception metabolic optimisation. This study cannot evaluate in-pregnancy safety or efficacy, and these findings do not support GLP-1/GIP RA use during gestation.