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A 5-week study of the pharmacokinetics and pharmacodynamics of LY2189265, a novel, long-acting glucagon-like peptide-1 analog, in patients with type 2 diabetes.
MedLine Citation:
PMID:  21251178     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Aims: To investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of LY2189265 (LY), a novel, long-acting GLP-1 analog, administered once-weekly to subjects with type 2 diabetes. Materials and Methods: This was a placebo-controlled, parallel-group, subject- and investigator-blind study of LY in subjects (N=43) with type-2 diabetes mellitus controlled with diet and exercise alone or with a single oral antidiabetic medication. Subjects taking metformin or thiazolidinediones continued on their therapy. Subjects receiving sulfonylurea, acarbose, repaglinide or nateglinide were switched to metformin prior to enrollment. Subjects received five once-weekly doses of 0.05, 0.3, 1, 3, 5 or 8 mg. Effects on glucose, insulin, and C-peptide concentrations were determined during fasting and following standard test-meals. The pharmacokinetics of LY2189265 and its effects on HbA1c, glucagon, body weight, gastric emptying and safety parameters were assessed. Results: Once-weekly administration of LY significantly reduced (p<0.01) fasting plasma glucose, 2h post-test meal postprandial glucose, and glucose AUC after test meals at doses ≥1 mg. These effects were seen after the first dose, and were sustained through the weekly dosing cycle. Most doses produced statistically significant increases in insulin and C-peptide AUC when normalized for glucose AUC. Statistically significant reductions in HbA1c were observed for all dose groups except 0.3 mg. The most commonly reported AEs were nausea (35 events), headache (20 events), vomiting (18 events), and diarrhea (8 events). Conclusions: LY demonstrated improvement in fasting and postprandial glycemic parameters when administered once-weekly in subjects with type 2 diabetes. The pharmacokinetics and safety profiles also support further investigation of this novel agent.
Authors:
P Barrington; J Y Chien; H D H Showalter; K Schneck; S Cui; F Tibaldi; B Ellis; T A Hardy
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-1-19
Journal Detail:
Title:  Diabetes, obesity & metabolism     Volume:  -     ISSN:  1463-1326     ISO Abbreviation:  -     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-1-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100883645     Medline TA:  Diabetes Obes Metab     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2011 Blackwell Publishing Ltd.
Affiliation:
Eli Lilly and Company, Erl Wood, United Kingdom Eli Lilly and Company, Indianapolis, Indiana, USA i3StatProbe, Austin, TX, USA GSK Biologicals, Rixensart, Belgium Global Statistical Sciences, Eli Lilly, Lilly Corporate Center, 46285 Indianapolis, Indiana, USA Eli Lilly and Company, Lilly Corporate Center, 46285 Indianapolis, Indiana, USA.
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