Enteral recombinant human insulin: A novel pharmacotherapy for feeding intolerance in preterm infants

Feeding intolerance is a common condition among preterm infants owing to immaturity of the gastrointestinal tract. Clinical symptoms consist of gastric residuals, vomiting, and/or abdominal distention. Feeding intolerance prolongs dependency on parenteral nutrition, which, in turn, is associated with an increased risk of complications (e.g., late-onset sepsis and intestinal failure-associated liver disease).
Preterm infants fed with mother’s own milk have a more rapid postnatal intestinal maturation, fewer clinical symptoms of feeding intolerance, and a lower risk of postnatal complications relative to preterm infants fed with formula. The intestinal stimulating effect of mother’s own milk appears attributed to its numerous nonnutritive bioactive factors, including the peptide hormone insulin. This thesis shows that the natural insulin concentration in human milk peaks in the early postpartum period but declines to a basal level within the first three days postpartum. The insulin concentration in donor human milk is significantly reduced by heat-dependent pasteurization techniques used in human milk banks. To date, insulin is absent in formula.
Therefore, a recombinant human (rh) insulin formulation has been developed for enteral administration in preterm infants. This thesis shows that enteral administration of two different rh-insulin dosages is safe, and, compared to placebo, significantly reduces time to achieve full enteral feeding in preterm infants with a gestational age of 26–32 weeks. Implementation of enteral rh-insulin in standard clinical practice may be considered once efficacy and safety have been confirmed in a second planned, adequately powered, randomized controlled trial in preterm infants.