Randomized controlled trial of insulin detemir versus NPH for the treatment of pregnant women with diabetes

Abstract

Objective: We sought to determine if insulin detemir (IDet) is noninferior to insulin neutral protamine Hagedorn (NPH) for the treatment of gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) in pregnancy.

Study design: We conducted a randomized, controlled noninferiority trial of women with GDM and T2DM who entered our Diabetes in Pregnancy Program from March 2013 through October 2014. Exclusion criteria were type 1 diabetes, age <18 years, and insulin allergy. Women who failed to achieve good glycemic control (GC) (mean blood glucose [BG] <100 mg/dL) on diet and/or hypoglycemic agents were randomized to receive either IDet or NPH, with short-acting insulin aspart added as needed. Patients were instructed to test BG 4 times a day (fasting and 2-hour postprandial). Targets of GC were fasting BG <90 mg/dL and postprandial BG <120 mg/dL, and insulin was adjusted as needed to achieve the targets. The primary outcome was overall mean BG during insulin treatment; secondary outcomes included overall mean postprandial and fasting BG, median number of weeks to achieve GC, percent of patients with overall GC, maternal weight gain, perinatal/neonatal outcomes, and number of hypoglycemic events. Power analysis (90% power) determined that 88 patients would need to be randomized, assuming a maximal acceptable difference in overall mean BG of 7 mg/dL (SD ± 10 mg/dL). A per protocol analysis was performed.

Results: In all, 105 women were randomized. Eighteen women were excluded leaving 87 participants for analysis (45 NPH, 42 IDet). Maternal characteristics were similar in both groups. The difference in the mean BG of the groups was 2.1 mg/dL with a 1-sided upper 95% confidence limit of 5.5 mg/dL (less than the maximal acceptable difference of 7 mg/dL; P = .2937). There was no significant difference in the primary outcome when an intent-to-treat analysis was performed or when the T2DM patients were excluded. The time to achieve GC was similar in both groups. There were no differences in perinatal outcomes and maternal weight gain among the groups. There were more hypoglycemic events per patient in the NPH group.

Conclusion: IDet is noninferior to insulin NPH for the treatment of GDM and T2DM in pregnancy.

Trial registration: ClinicalTrials.gov NCT01837680.

Keywords: gestational diabetes; insulin detemir; insulin neutral protamine Hagedorn; pregnancy; type 2 diabetes.