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Humulin® Therapies
Humulin® R (U-100) (regular insulin human injection, USP [rDNA origin])
100 units/mLHumulin® R (U-500) (regular U-500 [concentrated] insulin human injection, USP [rDNA origin])
500 units/mLHumulin® 70/30 (70% human insulin isophane suspension and 30% human insulin injection [rDNA origin])
100 units/mLHumulin® N U-100 (human insulin [rDNA origin] isophane suspension)
100 units/mLThis information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
What are the pharmacokinetics and pharmacodynamics of Humulin® R U-500 (insulin human injection)?
The time action characteristics reflect both prandial and basal activity attributed to the high concentration of Humulin R U‑500.
Detailed Information
The prandial and basal activity of Humulin® R U‑500 (insulin human injection) 500 units/mL (U‑500R) is consistent with clinical experience ().1-3
Reference/Study |
Study Design |
Results |
de la Peña A, et al1. |
Randomized, double-blind, single-site, crossover, euglycemic clamp study including 24 healthy subjects who were
Evaluated PK/PD of U‑500R and U‑100R administered as single SC injection of
Primary objective was relative exposure (AUC0-t’) for U‑500R and U‑100R. Secondary objectives included
|
Similar between U‑100R and U‑500R at both doses were
Significantly (p<.05) lower for U‑500R at both doses were
Significantly (p<.05) longer for U‑500R vs U‑100R at both doses was
Significantly (p<.05) longer for U‑500R at only the 100‑unit dose were
Authors concluded that
No severe TEAE was reported. No discontinuation due to AE. AEs reported included
|
de la Peña A, et al2. |
Simulation modeling PK/PD study with U‑500R derived from 3
Evaluated PK/PD of single-dose U‑500R in
Insulin doses:
Simulation profiles:
|
All 3 dosing regimens achieved steady-state PK by 24 hours post dose.
|
Hood RC, et al3. |
Randomized, prospective, open-label, multicenter, 24-week study, including 325 patients with T2DM taking >200 units of insulin/day. Compared the efficacy and safety of U‑500R dosed
Mean baseline demographics were
Primary objective was HbA1c change.c Secondary objective was 7-point SMPG profiles. Hypoglycemia definitions were
|
HbA1c change: LSM=0.10% (95% CI, -0.33 to 0.12%), supporting clinical equivalence between the 2 dosing regimens.d HbA1c reductions significant (p<.001) for both groups were
7-point SMPG profiles difference between groups were
Thrice-daily dosing resulted in a significantly lower incidence (p=.003) and rate of documented symptomatic hypoglycemia than twice-daily dosing (p=.02). There was no difference in the incidence or rate of severe hypoglycemia groups. The prandial/basal time-concentration/action characteristics of U‑500R provide explanation for the differences between the groups in
Higher rate of hypoglycemia in
|
Abbreviations: AE = adverse event; AUC0-t’ = area under the serum insulin concentration vs time curve from zero to return to baseline; BMI = body mass index; BW = body weight; HbA1c = glycated hemoglobin; LSM = least squares mean; PD = pharmacodynamics; PG = plasma glucose; PK = pharmacokinetics; SC = subcutaneous; SMPG = self-monitored plasma glucose; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus; TDI = total daily insulin; TEAE = treatment-emergent adverse event; U-100R = Humulin® R U-100 (insulin human injection) 100 units/mL; U-500R = Humulin® R U-500 (insulin human injection) 500 units/mL.
aMean value.
bCompared with twice-daily dosing.
cFrom baseline.
dPrespecified noninferiority margin of 0.4%.
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1de la Peña A, Riddle M, Morrow LA, et al. Pharmacokinetics and pharmacodynamics of high-dose human regular U-500 insulin versus human regular U-100 insulin in healthy obese subjects. Diabetes Care. 2014;37(8):2414. https://doi.org/10.2337/dc14-er08
2de la Peña A, Ma X, Reddy S, et al. Application of PK/PD modeling and simulation to dosing regimen optimization of high-dose human regular U-500 insulin. J Diabetes Sci Technol. 2014;8(4):821-829. http://dx.doi.org/10.1177/1932296814532326
3Hood RC, Arakaki RF, Wysham C, et al. Two treatment approaches for human regular U-500 insulin in patients with type 2 diabetes not achieving adequate glycemic control on high-dose U-100 insulin therapy with or without oral agents: a randomized, titration-to-target clinical trial. Endocr Pract. 2015;21(7):782-794. https://doi.org/10.4158/EP15612.OR
Date of Last Review: September 07, 2021