Treatment of gestational diabetes mellitus to a tighter glycemic target is not beneficial

Reference

Crowther CA, Samuel D, Hughes R, et al, for the TARGET Study Group. Tighter or less tight glycaemic target for women with gestational diabetes mellitus for reducing maternal and perinatal morbidity: A stepped-wise, cluster-randomised trial. PLoS Med 2022;19:e1004087.

Synopsis

This was a cluster-randomized trial of clinical implementation of a tight glycemic target for the treatment of gestational diabetes mellitus (GDM). Mothers with GDM between 22 weeks and 34 weeks of gestation based on a 2-hour (75g) oral glucose tolerance test were automatically enrolled in the study, which was a rollout of a change in care in New Zealand’s national healthcare system. The rollout was conducted in phases, with 10 hospitals randomized in cluster pairs at each of five 4-month intervals. For each pair, one hospital was randomized to the new tighter glycemic control target of a fasting glucose level of not more than 90 mg/dL and a 2-hour postprandial glucose level of not more than 121 mg/dL, and the other hospital continued prior standard targets of less than 99 mg/dL fasting and less than 144 mg/dL postprandial. Hospitals were notified 2 weeks prior to the implementation date of the new targets. Their personnel received training during that 2-week lead period. All patients received standard dietary and lifestyle counseling, blood glucose monitoring, and pharmacological treatment, as needed. The authors didn't report whether lower glucose targets were achieved. The primary outcome of incidence of a large-for-gestational-age infant did not differ between groups (88/599 [14.7%] in the study group vs 76/502 [15.1%] in the control group; adjusted relative risk [aRR] 0.96; 95% CI 0.66 - 1.40). A composite serious adverse outcome for infants included perinatal death, birth trauma, and shoulder dystocia. This composite outcome was not significantly different between groups (8/599 [1.3%] vs 13/505 [2.6%]; aRR 0.33; 0.10 - 1.08). The authors made further post hoc adjustments for gestational age at the diagnosis of GDM, body mass index, ethnicity, and history of GDM. With those adjustments, the calculated relative risk favored the tighter glucose targets, statistically significant at P = .03, which I don’t find convincing. A composite serious adverse outcome for mothers included maternal death, pulmonary edema, eclampsia, stroke, adult respiratory distress syndrome, cardiac arrest, respiratory arrest, placental abruption, hemolysis, coagulopathy, major postpartum hemorrhage, deep vein thrombosis, and pulmonary thromboembolism. This composite outcome occurred more frequently among women in the tight treatment groups (35/595 [5.9%] vs 15/501 [3.0%]; aRR 2.29; 1.14 - 4.59; P = .02; number needed to treat to harm = 27;15 - 144). Postpartum hemorrhage accounted for the majority of adverse maternal events in both groups (26/595 [4.4%] and 12/501 [2.4%]).