Gestational diabetes (a type of diabetes that occurs during pregnancy) is a common pregnancy complication. It can lead to adverse pregnancy outcomes to mother and child, including potential long-lasting health impacts (e.g., heart disease and type 2 diabetes). Proper control of blood sugar during pregnancy is crucial in preventing these long-term complications.
Drugs are usually given for women who do not achieve target blood sugar levels through lifestyle interventions such as diet or exercise. Although insulin is the recommended treatment for pregnant women with gestational diabetes, it is inconvenient for patients because it is administered by injection and because it requires increased medical visits for monitoring. Oral anti-diabetic drugs, such as metformin or glyburide may be potential alternative treatments. However, there are safety concerns surrounding their use during pregnancy that require further investigation. Currently, there is no clear consensus on the effectiveness and safety of using metformin or glyburide during pregnancy due to limitations of existing studies in this area.
Therefore, we aim to use information from the Clinical Practice Research Datalink (CPRD) to provide complementary evidence to current clinical trials with rigorous research methods. We will include all pregnant women in the CPRD between 1998 and 2018 with a gestational diabetes diagnosis. We will first describe the utilization of drugs used to treat gestational diabetes in terms of trends over time and patient characteristics. We will then investigate the effectiveness and safety of these oral anti-diabetic drugs vs. insulin on short-term and long-term health outcomes of mothers and their offspring.
Gestational diabetes mellitus (GDM), defined as glucose intolerance during pregnancy, has detrimental impacts on short and long-term health outcomes of mothers and offspring. Insulin is a first-line treatment for GDM not controlled through diet that creates patient burden with more medical visits and administration via injection. Oral hypoglycemic agents (OHAs), such as metformin or glyburide, may be viable alternatives to insulin, but placental drug permeation presents safety concerns requiring further investigation. There is no clear consensus on the effectiveness and safety of OHAs due to the limitations of the evidence, including small sample trials, different diagnostic criteria, and few long-term follow-up studies. Although OHA use has not been authorized during pregnancy, it is recommended in guidelines and frequently used off-label. It is crucial to quantify real-world use and to evaluate effectiveness and safety of OHAs versus insulin with large samples and appropriate methods.
Thus, we propose a comprehensive evaluation of GDM treatment in a populated-based cohort of women with GDM. We will (1) describe the utilization, patient demographic and clinical characteristics of GDM treatments; (2) examine the effectiveness and safety of GDM treatments on short-term outcomes (e.g., preterm birth, birth weight) and long-term outcomes (e.g. GDM recurrence). Using CPRD pregnancy registry, CPRD Gold, the mother-baby linkage, and Hospital Episode Statistics, our study will include all pregnancies from women with GDM and no prior history of diabetes identified from 1998 to March 2018. We will first describe the prescription patterns of different GDM treatments by year and maternal demographics and comorbidities. Binomial regression will estimate the risk difference and risk ratios of binary outcomes comparing use of metformin versus glyburide and metformin versus insulin. Marginal structural Cox models will be applied for time to event outcomes accounting for time-varying confounders by weighting by high-dimensional propensity score (hdPS).
Our outcomes of interest include maternal and perinatal outcomes (preterm birth, birth weight, small for gestational age (SGA), large for gestational age (LGA), macrosomia, neonatal hypoglycaemia, birth injury, neonatal intensive care unit (NICU) admission, glycemic control, preeclampsia, pregnancy-induced hypertension, gestational weight gain), in addition to offspring-related long-term outcomes (height, weight, body mass index (BMI), metabolic abnormality, neurodevelopment disorders (NDD), and maternal long-term outcomes (recurrence of GDM, incident type 2 diabetes)).
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Kristian Filion - Corresponding Applicant - McGill University
pauline reynier - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Robert Platt - Collaborator - McGill University
YA-HUI YU - Collaborator - Georgia State University
Ya-Hui Yu - Collaborator - McGill University
CPRD Mother-Baby Link;HES Admitted Patient Care;Patient Level Index of Multiple Deprivation;Pregnancy Register