title: Subcutaneous Injection Depth Does Not Affect the Pharmacokinetics or Glucodynamics of Insulin Lispro in Normal Weight or Healthy Obese Subjects.
abstract: BACKGROUND
  An 8-mm needle length is commonly used for insulin injections; however, recent recommendations suggest shorter needles may help patients avoid intramuscular injections and reduce pain, while maintaining adequate glucose control. The goal of these analyses was to compare the pharmacokinetics (PK) and glucodynamics (GD) of insulin lispro after a 5-mm or an 8-mm injection depth administration in 2 populations: normal weight (study 1) or obese (study 2).
  
  
  METHODS
  In both open-label, randomized, 2-period crossover euglycemic clamp studies, subjects received single 0.25 U/kg insulin lispro doses on 2 occasions (at 5-mm and 8-mm injection depths); samples for PK and GD analyses were collected up to 6 hours postdose. Noncompartmental PK parameters AUC0-tlast, AUC0-∞, Cmax and GD parameters Gtot, Rmax, tRmax were log-transformed prior to analysis using a mixed effects model.
  
  
  RESULTS
  There were no apparent differences between PK profiles at the 5-mm or 8-mm injection depth in either study, demonstrated by the ratios of geometric means of AUC0-tlast, AUC0-∞, and Cmax being close to 1, with 90% confidence intervals (CI) within (0.80, 1.25). There were no apparent differences between GD profiles at either injection depth with the ratios of Gtot and Rmax near unity and 90% CIs that included 1. In both studies, the tRmax values were similar between injection depths, with a small median of pairwise differences and a 90% CI that included zero.
  
  
  CONCLUSIONS
  Injection depths in the 5-8 mm range did not affect the PK or GD of insulin lispro in normal weight or obese subjects.
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA de_la_pena_amparo@lilly.com.
authors.forename: Amparo
authors.initials: A
authors.lastname: de la Peña
authors.affiliation: Lilly-NUS Centre for Clinical Pharmacology, Singapore.
authors.forename: Kwee P
authors.initials: KP
authors.lastname: Yeo
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Helle
authors.initials: H
authors.lastname: Linnebjerg
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Catton
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Shobha
authors.initials: S
authors.lastname: Reddy
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Brown-Augsburger
authors.affiliation: Profil Institute for Clinical Research, Chula Vista, CA, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Morrow
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Debra A
authors.initials: DA
authors.lastname: Ignaut
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis*; D015992:Body Mass Index; D001835:Body Weight; D018592:Cross-Over Studies; D005260:Female; D015309:Glucose Clamp Technique; D064368:Healthy Volunteers; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D007279:Injections, Subcutaneous; D061268:Insulin Lispro / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity; D012107:Research Design; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D061268:Insulin Lispro
keywords: glucodynamics; injection depth; insulin lispro; pharmacokinetics