| Comparison of pharmacodynamic intrasubject variability of insulin lispro protamine suspension and insulin glargine in subjects with type 1 diabetes. | |
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MedLine Citation:
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PMID: 20508081 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: The objective of the study was to evaluate pharmacodynamic (PD) intrasubject variability of a single, s.c. dose of insulin lispro protamine suspension (ILPS) compared with insulin glargine in subjects with type 1 diabetes mellitus and additionally, to compare the intrasubject variability of pharmacokinetic parameters of both insulins. DESIGN: This was a single-center, investigator-blinded and subject-blinded, two-arm, parallel, randomized, four-period study. During the replicate visits, subjects received a single s.c. 0.6 U/kg dose of either ILPS or glargine, and underwent 24-h euglycemic glucose clamps. RESULTS: The intrasubject variabilities of the primary PD parameters, total amount of glucose infused (G(tot)) and maximum glucose infusion rate (GIR; R(max)), were statistically significantly lower for ILPS when compared with glargine (P<0.0001). Least-square (LS) mean estimates for G(tot) and R(max) were 2512.7 mg/kg and 3.740 mg/min per kg respectively for ILPS, and 1291.9 mg/kg and 1.793 mg/min per kg respectively for glargine. The LS 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-h glucose-lowering activity. Glargine demonstrated a flatter GIR-time curve, and ILPS demonstrated a significantly shorter time of maximum GIR (tR(max)) and earlier time to half-maximal GIR before tR(max) and time to half-maximal GIR after tR(max). ILPS administration resulted in significantly greater exposure compared with glargine (area under the baseline-corrected serum concentration versus time curve from time 0 to 24 h (AUC(0-24)): 77 150 vs 53 111 pmol min/l; maximum serum insulin concentration (C(max)): 119 vs 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 a more predictable response. |
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Authors:
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S M Ocheltree; M Hompesch; E T Wondmagegnehu; L Morrow; K Win; S J Jacober |
Publication Detail:
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Type: Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't Date: 2010-05-27 |
Journal Detail:
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Title: European journal of endocrinology / European Federation of Endocrine Societies Volume: 163 ISSN: 1479-683X ISO Abbreviation: Eur. J. Endocrinol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-27 Completed Date: 2010-08-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9423848 Medline TA: Eur J Endocrinol Country: England |
Other Details:
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Languages: eng Pagination: 217-23 Citation Subset: IM |
Affiliation:
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Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Area Under Curve Blood Glucose Body Mass Index Diabetes Mellitus, Type 1 / blood, drug therapy* Double-Blind Method Female Glucose Clamp Technique Humans Hypoglycemic Agents / pharmacology, therapeutic use Individuality Insulin / analogs & derivatives*, blood, pharmacology, therapeutic use Male Middle Aged Statistics, Nonparametric |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Hypoglycemic Agents; 0/glargine; 11061-68-0/Insulin; 133107-64-9/insulin LISPRO |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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