Metformin use and preeclampsia risk in women with diabetes: a two-country cohort analysis

• Published in: BMC medicine 2024-09, Vol.22 (1), p.418-10, Article 418
• Main Authors: Gordon, Hannah, Salim, Noor, Tong, Stephen, Walker, Susan, De Silva, Manarangi, Cluver, Catherine, Mehdipour, Parinaz, Hiscock, Richard, Sutherland, Lauren, Doust, Ann, Bergman, Lina, Wikström, Anna-Karin, Lindquist, Anthea, Hesselman, Susanne, Hastie, Roxanne
• Format: Article
• Language: English
• Subjects: Adult; Allmän medicin; Antidiabetics; Authorship; Birth weight; Body mass index; Care and treatment; Cohort Studies; Complications and side effects; Confidence intervals; Confounding (Statistics); Country of birth; Data analysis; Diabetes in pregnancy; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - epidemiology; Diabetes, Gestational - drug therapy; Diabetes, Gestational - epidemiology; Dosage and administration; Family Medicine; Female; Gestational age; Gestational diabetes; Gestational hypertension; Health aspects; Humans; Hypertension; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; In vitro fertilization; Infant, Newborn; Meta-analysis; Metformin; Metformin - adverse effects; Metformin - therapeutic use; Morbidity; Neonates; Observational studies; Ovaries; Parent educational background; Polycystic ovary syndrome; Population; Pre-eclampsia; Pre-Eclampsia - epidemiology; Preeclampsia; Pregnancy; Pregnancy complications; Pregnancy-induced hypertension; Pregnant women; Premature birth; Prevention; Random variables; Regression analysis; Risk factors; Risk management; Risk reduction; Scotland - epidemiology; Socioeconomic factors; Socioeconomic status; Statistical analysis; Sweden - epidemiology; Womens health
• ISSN: 1741-7015; 1741-7015
• DOI: 10.1186/s12916-024-03628-0

Metformin is a hypoglycaemic medication that has been proposed to treat or prevent preeclampsia. Combining national birth data from Scotland and Sweden, we investigated whether metformin used during pregnancy was associated with an altered risk of developing a hypertensive disorder of pregnancy. We utilised data from two population-based cohorts: Scotland (2012-2018) and Sweden (2007-2019). Nulliparous women with gestational diabetes or type 2 diabetes who had birth outcome data linked with medications prescribed during pregnancy were included. The association between metformin prescription and hypertensive disorders of pregnancy was characterised using inverse probability weighted regression analysis, adjusting for variables that predict metformin use and potential confounders. Adverse neonatal outcomes were included as secondary outcomes. Results from both countries were then combined in a meta-analysis using a random effects model. The Scottish cohort included 3859 women with gestational diabetes or type 2 diabetes. Of these women, 30.8% (n = 1187) received at least one metformin prescription during pregnancy. For Sweden, 7771 women with gestational diabetes were included where 19.3% (1498) used metformin during pregnancy. Metformin prescription was not associated with an altered risk of any hypertensive disorder of pregnancy (Scotland adjusted relative risk (aRR) 0.88 [95% confidence interval (CI) 0.66-1.19]; Sweden aRR 1.08 [95% CI 0.86-1.37]) or preeclampsia (Scotland aRR 1.02 [95% CI 0.66-1.60]; Sweden aRR 1.00 [95% CI 0.72-1.39]). Combining adjusted results in a meta-analysis produced similar findings, with a pooled RR of 0.98 (95% CI 0.79-1.18) for any hypertensive disorder and RR 1.01 ([95% CI 0.73-1.28]) for preeclampsia. For neonatal outcomes, metformin was associated with a reduced risk of birthweight > 4500 g in Scotland (aRR 0.39 [95% CI 0.21-0.71]) but not in Sweden. There was no association between metformin and preterm birth or birthweight