title: Basal insulin peglispro demonstrates preferential hepatic versus peripheral action relative to insulin glargine in healthy subjects.
abstract: OBJECTIVE
  We evaluated the endogenous glucose production (EGP) and glucose disposal rate (GDR) over a range of doses of basal insulin peglispro (BIL) and insulin glargine in healthy subjects.
  
  
  METHODS
  This was a single-center, randomized, open-label, four-period, incomplete-block, crossover study conducted in eight healthy male subjects. Subjects had 8-h euglycemic clamps performed with primed, continuous infusions of BIL (5.1 to 74.1 mU/min) in three dosing periods and insulin glargine (20 or 30 mU/m(2)/min) in a fourth period, targeted to achieve 50-100% suppression of EGP. D-[3-(3)H] glucose was infused to assess rates of glucose appearance and disappearance.
  
  
  RESULTS
  Mean BIL and insulin glargine concentrations (targeted to reflect the differences in intrinsic affinities of the two basal insulins) ranged from 824 to 11,400 and 212 to 290 pmol/L, respectively, and increased accordingly with increases in dose. Suppression of EGP and stimulation of GDR were observed with increasing concentrations of both insulins. At insulin concentrations where EGP was significantly suppressed, insulin glargine resulted in increased GDR. In contrast, at comparable suppression of EGP, BIL had minimal effect on GDR at lower doses and had substantially less effect on GDR than insulin glargine at higher doses.
  
  
  CONCLUSIONS
  The novel basal insulin analog BIL has relative hepatopreferential action and decreased peripheral action, compared with insulin glargine, in healthy subjects.
authors.affiliation: Center for Metabolic Research, VA San Diego Healthcare System, San Diego, CA University of California, San Diego, La Jolla, CA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Henry
authors.affiliation: Center for Metabolic Research, VA San Diego Healthcare System, San Diego, CA University of California, San Diego, La Jolla, CA.
authors.forename: Sunder
authors.initials: S
authors.lastname: Mudaliar
authors.affiliation: Center for Metabolic Research, VA San Diego Healthcare System, San Diego, CA University of California, San Diego, La Jolla, CA.
authors.forename: Theodore P
authors.initials: TP
authors.lastname: Ciaraldi
authors.affiliation: Center for Metabolic Research, VA San Diego Healthcare System, San Diego, CA.
authors.forename: Debra A
authors.initials: DA
authors.lastname: Armstrong
authors.affiliation: Center for Metabolic Research, VA San Diego Healthcare System, San Diego, CA.
authors.forename: Paivi
authors.initials: P
authors.lastname: Burke
authors.affiliation: University of California, San Diego, La Jolla, CA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Pettus
authors.affiliation: Eli Lilly and Company, Indianapolis, IN.
authors.forename: Parag
authors.initials: P
authors.lastname: Garhyan
authors.affiliation: Eli Lilly and Company, Singapore, Singapore.
authors.forename: Siak Leng
authors.initials: SL
authors.lastname: Choi
authors.affiliation: Eli Lilly and Company, Indianapolis, IN.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Jacober
authors.affiliation: Eli Lilly and Company, Indianapolis, IN.
authors.forename: Mary Pat
authors.initials: MP
authors.lastname: Knadler
authors.affiliation: Eli Lilly and Company, Singapore, Singapore.
authors.forename: Eric Chen Quin
authors.initials: EC
authors.lastname: Lam
authors.affiliation: Eli Lilly and Company, Indianapolis, IN.
authors.forename: Melvin J
authors.initials: MJ
authors.lastname: Prince
authors.affiliation: University of California, San Diego, La Jolla, CA.
authors.forename: Namrata
authors.initials: N
authors.lastname: Bose
authors.affiliation: Eli Lilly and Company, Indianapolis, IN.
authors.forename: Niels
authors.initials: N
authors.lastname: Porksen
authors.affiliation: Eli Lilly and Company, Indianapolis, IN.
authors.forename: Vikram P
authors.initials: VP
authors.lastname: Sinha
authors.affiliation: Eli Lilly and Company, Indianapolis, IN linnebjerg_helle@lilly.com.
authors.forename: Helle
authors.initials: H
authors.lastname: Linnebjerg
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects*; D015331:Cohort Studies; D018592:Cross-Over Studies; D015309:Glucose Clamp Technique; D064368:Healthy Volunteers; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000069036:Insulin Glargine; D061268:Insulin Lispro / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D049528:Insulin, Long-Acting / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008099:Liver / Q000187:drug effects*; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro; D049528:Insulin, Long-Acting; C000621851:basal insulin peglispro; D000069036:Insulin Glargine; D011092:Polyethylene Glycols