Real-world experience of metformin use in pregnancy: Observational data from the Northern Territory Diabetes in Pregnancy Clinical Register.

Louise J Maple-Brown, Greta Lindenmayer, Federica Barzi, Cherie Whitbread, Christine Connors, Elizabeth Moore, Jacqueline Boyle, Marie Kirkwood, I-Lynn Lee, Danielle Longmore, Paula van Dokkum, Mary Wicks, Michelle Dowden, Chrissie Inglis, Margaret Cotter, Renae Kirkham, Sumaria Corpus, Sridhar Chitturi, Sujatha Thomas, Kerin O'Dea, Paul Zimmet, Jeremy Oats, Harold D McIntyre, Alex Brown, Jonathan E Shaw

Journal: Journal of diabetes 2020;11(9):761-770

PMID: 30680949

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Abstract

BACKGROUND

In Australia's Northern Territory, Indigenous mothers account for 33% of births and have high rates of hyperglycemia in pregnancy. The prevalence of type 2 diabetes (T2D) in pregnancy is up to 10-fold higher in Indigenous than non-Indigenous Australian mothers, and the use of metformin is common. We assessed birth outcomes in relation to metformin use during pregnancy from a clinical register.

METHODS

The study included women with gestational diabetes (GDM), newly diagnosed diabetes in pregnancy (DIP), or pre-existing T2D from 2012 to 2016. Data were analyzed for metformin use in the third trimester. Regression models were adjusted for maternal age, body mass index, parity, and insulin use.

RESULTS

Of 1649 pregnancies, 814 (49.4%) were to Indigenous women, of whom 234 (28.7%) had T2D (vs 4.6% non-Indigenous women; P < 0.001). Metformin use was high in Indigenous women (84%-90% T2D, 42%-48% GDM/DIP) and increased over time in non-Indigenous women (43%-100% T2D, 14%-35% GDM/DIP). Among Indigenous women with GDM/DIP, there were no significant differences between groups with and without metformin in cesarean section (51% vs 39%; adjusted odds ratio [aOR] 1.25, 95% confidence interval [CI] 0.87-1.81), large for gestational age (24% vs 13%; aOR 1.5, 95% CI 0.9-2.5), or serious neonatal adverse events (9.4% vs 5.9%; aOR 1.32, 95% CI 0.68-2.57). Metformin use was independently associated with earlier gestational age (37.7 vs 38.5 weeks), but the risk did not remain independently higher after exclusion of women managed with medical nutrition therapy alone, and the increase in births <37 weeks was not significant on multivariate analysis.

CONCLUSIONS

We found no clear evidence of any adverse outcomes related to the use of metformin for the treatment of hyperglycemia in pregnancy.

Address: Wellbeing and Preventable Chronic Diseases Division, Menzies School of Health Research, Darwin, Northern Territory, Australia.; Division of Medicine, Royal Darwin Hospital, Darwin, Northern Territory, Australia.; Wellbeing and Preventable Chronic Diseases Division, Menzies School of Health Research, Darwin, Northern Territory, Australia.; Northern Territory Department of Health, Darwin, Northern Territory, Australia.; Aboriginal Medical Services Alliance Northern Territory, Darwin, Northern Territory, Australia.; Wellbeing and Preventable Chronic Diseases Division, Menzies School of Health Research, Darwin, Northern Territory, Australia.; Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.; Department of Medicine, Alice Springs Hospital, Alice Springs, Northern Territory, Australia.; Population Health Research, Baker Heart and Diabetes Institute, Alice Springs, Northern Territory, Australia.; Department of Medicine, Alice Springs Hospital, Alice Springs, Northern Territory, Australia.; One Disease, Darwin, Northern Territory, Australia.; Healthy Living NT, Darwin, Northern Territory, Australia.; Danila Dilba Health Service, Darwin, Northern Territory, Australia.; Division of Medicine, Royal Darwin Hospital, Darwin, Northern Territory, Australia.; Obstetrics and Gynaecology Department, Royal Darwin Hospital, Darwin, Northern Territory, Australia.; Population Health Research, University of South Australia, Adelaide, South Australia, Australia.; Department of Medicine, Central Clinical School, Monash University, Melbourne, Victoria, Australia.; Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.; Mater Medical Research Institute, University of Queensland, Brisbane, Queensland, Australia.; Obstetrics and Gynaecology Department, Royal Darwin Hospital, Darwin, Northern Territory, Australia.; South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.; Population Health Research, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.

DOI: 10.1111/1753-0407.12905

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MeSH Terms: Adult, Australia, Biomarkers, Birth Weight, Blood Glucose, Case-Control Studies, Diabetes Mellitus, Type 2, Diabetes, Gestational, Female, Follow-Up Studies, Gestational Age, Humans, Hypoglycemic Agents, Metformin, Northern Territory, Population Groups, Prediabetic State, Pregnancy, Pregnancy Outcome, Prognosis