1. Type of subcutaneous insulin and action towards achieving a physiological profile.

Type of Insulin	Action
Short‐ and rapid‐acting insulin
Lispro	Amino acid substitutions (inverting lysine at position 28 and proline at position 29 on the β‐chain of the insulin molecule), monomeric in tissues (Magon 2014; Home 2015). Peak insulin action achieved within 1 hour after injection and duration of action 2 to 4 hours (Durnwald 2008). Antibody levels not increased over those seen with regular human insulin. Does not seem to cross the placenta (Jovanovic 2007)
Aspart	Amino acid substitutions (proline at position 28 on the β‐chain of the insulin molecule with negatively charged aspartic acid), monomeric in tissues (Magon 2014; Home 2015). Peak action 31‐70 minutes for 2 to 4 hours and lowers postprandial glucose levels significantly better than human insulin (Jovanovic 2007; Magon 2014). No evidence that insulin aspart is teratogenic (Hod 2005)
Glulisine	Amino acid substitutions and reformulation, rapidly monomeric in tissues (Home 2015). Produces peak blood glucose level at 15‐20 minutes and lowers postprandial glucose levels significantly better than human insulin (Jovanovic 2007). Adverse effects on embryo‐fetal development were only seen at animal maternal toxic dose levels inducing hypoglycaemia. No clinical data currently available for the use of Insulin glulisine in pregnancy (Magon 2014)
Intermediate‐ and long‐acting insulin
Neutral Protamine Hagedorn (NPH)	Protamine crystal suspension (Home 2015). NPH has an onset of action approximately after 90 minutes and a duration of action up to 16 to 18 hours (Jovanovic 2007; Magon 2014). No randomised controlled trials currently to confirm safety during pregnancy but several case reports and one case‐control study indicate no fetal morbidity or macrosomia (Magon 2014)
Detemir	Slowly absorbed and binds to albumin through a fatty‐acid chain attached to the lysine at residue B29 resulting in reduction in its free level which slows distribution to peripheral target tissues with a duration of action of up to 24 hours (Magon 2014). Significant improvement in fasting plasma glucose with insulin detemir during pregnancy for T1DM without an increased incidence of hypoglycaemia, including at night. No adverse maternal or neonatal effects were identified (Mathiesen 2012; Callesen 2013; Hod 2014). Suffecool 2015 conducted a small study including 11 women with GDM and five women with type 2 diabetes receiving detemir assessing maternal and cord blood at birth. The results showed that while maternal detemir levels were in the expected range for adults, the hormone was undetectable in the cord blood, indicating that detemir does not cross the human placenta. Larger studies and randomised controlled trials are needed to confirm
Glargine	Slowly absorbed and replaces the human insulin amino acid asparagine at position A21 of the A chain with glycine and two arginine molecules are added to one end (C‐terminal) of the B‐chain with onset of action approximately after 90 minutes of injection and lasting for about 24 hours (Price 2007; Ansar 2013). Studies in non‐pregnant participants have indicated that insulin glargine has a smooth peak‐free profile of action, with a reduced incidence of nocturnal hypoglycaemia and better glycaemic control (Graves 2006; Magon 2014; Woolderink 2005). Concerns regarding insulin glargine’s use in pregnancy are raised from case‐control, case reports and retrospective studies (including women with T1DM, T2DM and some with GDM) that have shown six‐ to eight‐fold increased affinity for insulin growth factor (IGF)‐1 receptor compared with human insulin. However, results of these studies found no association with increased fetal macrosomia or neonatal morbidity with the use of glargine in pregnancy (Bolli 2000; Egerman 2009; Lv 2015; Pöyhönen‐Alho 2007). No randomised controlled trials currently to confirm safety during pregnancy

AbbreviationL GDM ‐ gestational diabetes mellitus; T1DM ‐ type 1 diabetes mellitus; T2DM ‐ type 2 diabetes mellitus