Insulin analogues and other developments in insulin therapy for diabetes

Accelerated Pharmacokinetics and Glucodynamics of Prandial Insulins Injected With Recombinant Human Hyaluronidase

“…23 Co-injection of rHuPH20 reduced the intersubject variability of several key pharmacokinetic and glucodynamic parameters; this effect was observed with both Humalog and Humulin R. These intersubject variability findings indirectly suggest that intrasubject variability may also be reduced with rHuPH20 coadministration. Greater predictability of insulin absorption and consequent glucodynamic effects across a group of patients could allow simplified insulin dosing instructions to be used.…”

“…17,21,22 The slow onset of regular human insulin results largely from its hexameric structure; subcutaneous absorption is delayed until insulin is dissociated into monomeric form. 23 The fast-acting insulin analogs (e.g., insulin lispro) were developed to dissociate more rapidly, thus facilitating faster capillary absorption. 23 Co-administration of rHuPH20 with regular insulin or rapid-acting insulin analogues would enhance dispersion and thus should accelerate pharmacokinetic and glucodynamic parameters of either of these insulin formulations.…”

“…23 The fast-acting insulin analogs (e.g., insulin lispro) were developed to dissociate more rapidly, thus facilitating faster capillary absorption. 23 Co-administration of rHuPH20 with regular insulin or rapid-acting insulin analogues would enhance dispersion and thus should accelerate pharmacokinetic and glucodynamic parameters of either of these insulin formulations. The objectives of the current study were to compare the pharmacokinetic insulin time-concentration profile and glucodynamics of fast-acting insulin lispro (Humalog Ò , Eli Lilly and Co., Indianapolis, IN) and, separately, regular human insulin (Humulin Ò R, Eli Lilly and Co.) when administered alone or in combination with rHuPH20 and to determine the safety and tolerability of these injections.…”

Insulin degludec: overview of a novel ultra long‐acting basal insulin

“…While NPH insulin is injected as a precipitate, these analogues achieve protracted absorption through other mechanisms, described below, meaning they can be injected as clear solutions. This avoids the risk of incomplete re‐suspension of the formulation before injection and hence removes a well‐recognized source of injection‐to‐injection variability in pharmacodynamic (PD) effect . Glargine and detemir produce more prolonged and less peaked PD responses than NPH insulin, and both analogues produce lower intra‐patient injection‐to‐injection variability in glucose‐lowering effect .…”

Subcutaneous injection of hyaluronidase with recombinant human insulin compared with insulin lispro in type 1 diabetes

“…The time required for absorption of regular insulin leads to a delay in the onset of action, and a longer duration of action relative to physiological insulin response. The latter contributes to late hypoglycaemic episodes . Rapid‐acting insulin analogues (e.g.…”