Basal insulin analogues in diabetic pregnancy: a literature review and baseline results of a randomised, controlled trial in type 1 diabetes

Abstract

As basal insulin analogues are being used off-label, there is a need to evaluate their safety (maternal hypoglycaemia and fetal and perinatal outcomes) and efficacy [haemoglobin A1c(HbA1c), fasting plasma glucose, and maternal weight gain]. The aim of this review is to provide an overview of the current literature concerning basal insulin analogue use in diabetic pregnancy, and to present the design and preliminary, non-validated baseline characteristics of a currently ongoing randomized, controlled, open-label, multicentre, multinational trial comparing insulin detemir with neutral protamine hagedorn insulin, both with insulin aspart, in women with type 1 diabetes planning a pregnancy (n = 306) or are already pregnant (n = 164). Inclusion criteria include type 1 diabetes > 12 months' duration; screening HbA1c ≤ 9.0% (women recruited prepregnancy), or pregnant with gestational age 8-12 weeks and HbA1c ≤ 8.0% at randomization. At confirmation of pregnancy all subjects must have HbA1c ≤ 8.0%. Exclusion criteria include impaired hepatic function, cardiac problems, and uncontrolled hypertension. Subjects are randomized to either insulin detemir or neutral protamine hagedorn insulin, both with prandial insulin aspart. The results are expected mid-2011 with full publications expected later this year. Baseline characteristics show that basal insulin analogues are already frequently used in pregnant women with type 1 diabetes. This study will hopefully elucidate the safety and efficacy of the basal insulin analogue detemir in diabetic pregnancy.

A randomized trial comparing perinatal outcomes using insulin detemir or neutral protamine Hagedorn in type 1 diabetes

“…In contrast, few studies have examined the efficacy and safety of long-acting analogs in women with type 1 diabetes during pregnancy, despite their increasing use in this subject group. Consequently, basal insulin analogs have been used off-label [15]. Only one randomized controlled trial, described here, has investigated a basal analog, comparing insulin detemir (IDet) with neutral protamine Hagedorn (NPH), both in combination with insulin aspart (IAsp), in pregnant women with type 1 diabetes [16].…”

Comments on gestational diabetes mellitus: from pathophysiology to clinical practice

“…43 The main study outcome was the achievement of glycemic control, assessed by HbA1c, during gestational week 36; secondary outcomes were the effectiveness and safety of insulin detemir in terms of pregnancy outcome. Insulin detemir achieved comparable glycemic control, levels of HbA1c and number of hypoglycemic episodes compared with insulin NPH.…”

“…Insulin detemir resulted in significantly decreased fasting glucose and comparable pregnancy outcome. 43 According to the recent Endocrine society guidelines, 25 insulin detemir may be initiated during pregnancy whenever it is suspected that NPH insulin might result in hypoglycemia. Women taking insulin detemir or insulin glargine before pregnancy may continue their use throughout pregnancy.…”

Insulin analogues in the treatment of diabetes in pregnancy

“…The results found so far that detemir insulin is not inferior compared with NPH insulin in pregnant women with type 1 diabetes. This study will hopefully elucidate the safety and efficacy of the basal insulin analogue detemir in diabetic pregnancy (57).…”