Long-acting insulin analogue

Insulin is a peptide hormone acting as a key regulator of glucose homeostasis. Insulin binds to the insulin receptor (InsR), which exists in two alternatively spliced isoforms, InsR-A and InsR-B. The insulin receptor belongs to the same family of receptor tyrosine kinases as the IGF1 receptor (IGF1R) and insulin is therefore also able to bind to the IGF1R albeit with considerably lower affinity as compared to the insulin receptor.

NNC0100-0454 (also known as insulin degludec) is a long-acting insulin analogue with a C16 fatty diacid attached to lysine at position B29 (B29K) via a γ-L-glutamic acid linker and is therefore able to reversibly bind to serum albumin. In the marketed formulation containing zinc and phenol, this insulin analogue forms a depot of soluble multi-hexamers in the subcutis after subcutaneous injection. Over time the multi-hexamers slowly dissociate into monomeric entities that are absorbed into the circulation and through the fatty acid bind to albumin. These properties contribute to the long PK profile of NNC0100-0454.