Comparative effectiveness of metformin versus insulin for gestational diabetes in New Zealand

Abstract

Purpose To measure the comparative effectiveness of metformin versus insulin for initial pharmacological management of gestational diabetes mellitus (GDM). Methods We conducted a population‐based retrospective cohort study using administrative claims, maternity care, and laboratory result data from New Zealand. We followed pregnant women aged 15 to 45 from GDM diagnosis through delivery and assessed outcomes using maternity care and hospitalization data. We adjusted for covariates using inverse probability of treatment weights and multiple imputation for missing covariate information. We estimated unadjusted and adjusted risk ratios (RRs), risk differences (RDs) per 100, and 95% confidence intervals (CIs). Linear regression was used to estimate the association of treatment with birthweight. We stratified analyses by ethnicity and infant sex in prespecified sensitivity analyses. Results We compared 3818 metformin‐treated pregnancies with 3450 insulin‐treated pregnancies. We observed differences in treatment initiation by ethnicity, socioeconomic status, region, and calendar year. Treatment groups were similar in age, body mass index (BMI), and timing of diagnosis/treatment initiation. After adjustment, metformin was associated with reduced absolute risk of planned elective c‐section (RD = −2.3, 95% CI, −4.3 to −0.3), large for gestational age (RD = −3.7, 95% CI, −5.5 to −1.8), and neonatal hypoglycemia (RD = −5.0, 95% CI, −6.9 to −3.2) compared with insulin. There were no clinically meaningful differences in average birthweight between metformin‐ and insulin‐treated pregnancies. We observed variation in estimates by ethnicity and infant sex for some neonatal outcomes. Conclusion Metformin appears to be an effective treatment for women with GDM and may reduce risk of some adverse neonatal outcomes when compared with insulin.

Research progress of metformin in gestational diabetes mellitus: a narrative review

“…One RCT found that newborn birth weight of the metformin group was lower compared to the insulin group, indicating that metformin could reduce the newborn birth weight to some degree (77). In addition, we found that several meta-analyses showed that metformin reduced birth weights of newborns compared with insulin (45,66,67); however, a recent retrospective cohort study showed no clinically significant difference in neonatal mean birth weight between pregnant women treated with metformin and insulin (63). Another RCT showed no statistically significant difference in the average birth weight between metformin and insulin treatment groups (54).…”

“…Therefore, to further understand the therapeutic effect of metformin on GDM, we summarized some studies on the control of blood glucose by metformin in pregnant women with GDM to further explore the effect of metformin on blood glucose in GDM in Table 1 (35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51). At the same time, we also summarized the randomized controlled trials (36-37, 39-41,52-57), observational studies (43,(58)(59)(60)(61)(62)(63) and metaanalyses (34,(44)(45)(46)(47)(48)(49)(50)(51)(64)(65)(66)(67)(68)(69) of the effects of metformin on maternal and infant outcomes of pregnant women with GDM, and discussed the effects of metformin on maternal and infant outcomes in GDM in Table 2.…”

“…A recent retrospective cohort study (63) found that metformin significantly reduced the incidence of neonatal hypoglycemia in pregnant women with GDM compared with insulin treatment. One RCT found that neonatal hypoglycemia was higher in the insulin group than in the metformin group (38), while recent meta-analysis suggested that the risk of neonatal hypoglycemia in the metformin group was lower than in the insulin group (34,69).…”

Das metabolische Syndrom und Schwangerschaft

“…Es scheint daher naheliegend, dass -zumindest in Bezug auf die Adipositas des Kindes -eine Lifestyle-Modifikation mit präkonzeptionellem Gewichtsverlust durch Ernährungsumstellung und körperliche Betätigung nicht nur der Mutter, sondern auch dem Kindsvater empfohlen werden sollte [21]. [23,24].…”

Lactational Metformin Treatment in Mouse Dams Ameliorates Maternal High-Fat Diet-induced Metabolic Complications in Male Offspring

“…Due to its ability to cross the placenta and limited long-term safety data on offspring, clinical use of metformin in the treatment of gestational has been concerned [10,11]. However, there is accumulating evidence both in animals and humans indicated that metformin is an effective and safe option for the treatment of diabetes during pregnancy and breastfeeding, providing some metabolic benefits on offspring compared to insulin without adverse effects on long-term growth and development [12,13]. However, most of these animal studies investigated the effects of maternal metformin exposure throughout both gestation and lactation periods or just focusing on the gestation period.…”