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This Article Accepted manuscript (PDF) All Versions of this Article: EJE-09-1086v1 163/2/217    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ocheltree, S. Articles by Jacober, S. PubMed PubMed Citation Articles by Ocheltree, S. Articles by Jacober, S.

Comparison of pharmacodynamic intrasubject variability of insulin lispro protamine suspension and insulin glargine in subjects with type 1 diabetes

S Ocheltree, Program Phase Research, Eli Lilly and Company, Indianapolis, United States
M Hompesch, Profil Institute for Clinical Research, Inc., Chula Vista, United States
E Wondmagegnehu, Program Phase Statistics, Eli Lilly and Company, Indianapolis, United States
L Morrow, Profil Institute for Clinical Research, Inc., Chula Vista, United States
K Win, Profil Institute for Clinical Research, Inc., Chula Vista, United States
S Jacober, Insulins Medical, Eli Lilly and Company, Indianapolis, United States

Correspondence: Scott Jacober, Email: sjacober{at}lilly.com

Objective: The objective was to evaluate pharmacodynamic (PD) intrasubject variability of a single, subcutaneous (SC) dose of insulin lispro protamine suspension (ILPS) compared to insulin glargine in subjects with type 1 diabetes mellitus (T1DM) and additionally, to compare the intrasubject variability of pharmacokinetic (PK) parameters of both insulins.

Design: This was a single-center, investigator-blinded and subject-blinded, 2-arm, parallel, randomized, 4-period study. During the replicate visits, subjects received a single subcutaneous 0.6 U/kg dose of either ILPS or glargine and underwent 24-hour euglycemic glucose clamps.

Results: The intrasubject variabilities of the primary PD parameters, G_tot and R_max, were statistically significantly lower for ILPS when compared with glargine (p<0.0001). Least square mean estimates for G_tot and R_max were 2512.7 mg/kg and 3.740 mg/min/kg, respectively, for ILPS and 1291.9 mg/kg and 1.793 mg/min/kg, respectively, for glargine. The least square mean estimates for G_tot and R_max were statistically greater (p=0.0010 and p<0.0001, respectively) for ILPS compared with glargine, suggesting that ILPS had greater 24-hour glucose-lowering activity. Glargine demonstrated a flatter GIR-time curve and ILPS demonstrated a significantly shorter tR_max and earlier early 50% tR_max and late 50% tR_max. ILPS administration resulted in significantly greater exposure compared with glargine (AUC_0-24: 77 150 versus 53 111 pmol•min/L; C_max: 119 versus 68 pmol/L; ILPS versus glargine, respectively), but the intrasubject variabilities for AUC and C_max were comparable.

Conclusion: Although glargine demonstrated a flatter GIR-time profile, the lower PD intrasubject variability of ILPS may provide more a predictable response.