Question
What is the relationship between NovoLog and Humalog? Molecular structure aside, can they be directly substituted for each other?
Response From Expert
Mario M. Zeolla, PharmD, BCPS
Associate Professor, Department of Pharmacy Practice, Albany College of Pharmacy, New York; Patient Care Pharmacist, Eckerd Patient Care Center, Loudonville, New York
Insulin aspart (NovoLog, made by Novo Nordisk) and insulin lispro (Humalog, made by Eli Lilly) are rapid-acting insulin analogs indicated for treatment of type 1 and type 2 diabetes. Some institutions do substitute these agents for one another. Their pharmacokinetic parameters as reported in the product information are very similar. A number of small clinical trials have been performed comparing their pharmacokinetic and pharmacodynamic profiles, which suggest that few meaningful differences exist between the 2 products.
A randomized, double-blind, cross-over trial of patients with type 1 diabetes was performed to determine differences in the pharmacokinetic and pharmacodynamic profiles of insulin aspart and insulin lispro. Twenty-four subjects were given a single prandial dose of each agent tailored to individual dosing needs. Blood samples drawn before and after insulin administration demonstrated no statistical differences in relative blood glucose concentrations between the 2 agents over a 6-hour period. Similarly, there were no statistical differences in pharmacokinetic parameters, including peak insulin concentrations, insulin area-under-the-curve (AUC) at 4 and 6 hours, and time to peak insulin concentrations. The authors concluded that the 2 agents were equally effective.
However, an earlier study also performed in subjects with type 1 diabetes found some differences in pharmacokinetic parameters between the 2 agents. Fourteen subjects were randomized to a single dose of each agent before a standardized breakfast, with the alternate agent given to each subject after a 5- to 21-day washout period. While there were no statistically significant differences in glucose levels or insulin AUC between the agents over a 4-hour period, insulin lispro demonstrated more rapid absorption and elimination. These differences were statistically significant, but the clinical importance remains questionable, given the similar effects seen on glucose values.
A third study done in healthy volunteers had contrasting results, with insulin aspart demonstrating more rapid absorption and higher peak insulin concentrations. Again, absolute differences in pharmacokinetic parameters were statistically significant but small, and likely insignificant from a clinical standpoint.
Any differences in pharmacokinetic parameters are unlikely to be clinically relevant, and as such, these 2 agents may be interchanged. However, it is important to keep in mind that the pharmacokinetics and clinical response to all insulin products can vary between individuals due to a variety of factors. Individual patients switched from 1 agent to the other should be especially cautious about monitoring their blood glucose initially after the change.
A third rapid-acting insulin analogue, insulin glulisine (Apidra, made by Aventis), recently came to market. This agent appears to be more rapidly absorbed than the other 2 drugs. Head-to-head studies comparing these agents are not available, so substituting insulin glulisine for aspart or lispro should be avoided at this point.