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

Presented in poster format at the 35th annual meeting of the Society for Maternal-Fetal Medicine, San Diego, CA, Feb. 2-7, 2015.
https://doi.org/10.1016/j.ajog.2015.06.010Get rights and content

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.

Section snippets

Materials and Methods

This open-label, noninferiority, randomized study was conducted between March 2013 and January 2015. The study was approved by the institutional review board (#12-166) of Mount Sinai Roosevelt Hospital and was registered in ClinicalTrials.gov (NCT01837680). Eligible subjects were all pregnant women with a viable singleton or twin gestation, with either preexisting T2DM or GDM at ≤34 weeks, in need of medical therapy, who received care at our institution. GDM was diagnosed based on a positive

Results

During the study period of March 2013 through October 2014, 740 women entered the DIPP. In all, 635 women were excluded, leaving 105 women consented for randomization (53 to the NPH group, and 52 to the detemir group). In the detemir group, 46 patients received the allocation for the duration of treatment and 6 patients did not as they had an allergic reaction. Two patients were lost to follow-up, and 2 discontinued the detemir due to personal preference and switched to an oral hypoglycemic

Comment

From our data, we conclude that IDet is noninferior to insulin NPH for the treatment of GDM and T2DM in pregnancy. We have demonstrated this by using multiple analyses to validate and corroborate our results. First, by using a mixed effects model to analyze the primary outcome, we were able to account for the fact that patients came to follow-up visits at variable time intervals and therefore we may have overrepresentation of glucose data obtained over short intervals. Secondly, we have

Acknowledgments

We thank Sophia Scarpelli, RN, CDE, and Debi Lee, RN, CDE, of Roosevelt Hospital Diabetes in Pregnancy Program, Member of Mount Sinai Health System. They have no disclosures of financial funding.

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The authors report no conflict of interest.

Cite this article as: Herrera KM, Rosenn BM, Foroutan J, et al. Randomized controlled trial of insulin detemir versus NPH for the treatment of pregnant women with diabetes. Am J Obstet Gynecol 2015;213:426.e1-7.

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