| Encapsulation of Exenatide in Poly-(d,l-Lactide-Co-Glycolide) Microspheres Produced an Investigational Long-Acting Once-Weekly Formulation for Type 2 Diabetes. | |
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MedLine Citation:
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PMID: 21751887 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Abstract Exenatide once-weekly (EQW [2 mg s.c.]) is under development as monotherapy as an adjunct to diet and exercise or as a combination therapy with an oral antidiabetes drug(s) in adults with type 2 diabetes. This long-acting formulation contains the active ingredient of the original exenatide twice-daily (EBID) formulation encapsulated in 0.06-mm-diameter microspheres of medical-grade poly-(d,l-lactide-co-glycolide) (PLG). After mechanical suspension and subcutaneous injection by the patient, EQW microspheres hydrate in situ and adhere to one another to form an amalgam. A small amount of loosely bound surface exenatide, typically less than 1%, releases in the first few hours, whereas drug located in deeper interstices diffuses out more slowly (time to maximum, ∼2 weeks). Fully encapsulated exenatide (i.e., drug initially inaccessible to diffusion) releases over a still longer period (time to maximum, ∼7 weeks) as the PLG matrix hydrolyzes into lactic acid and glycolic acid, which are subsequently eliminated as carbon dioxide and water. For EQW, plasma exenatide concentrations reach the therapeutic range by 2 weeks and steady state by 6-7 weeks. This gradual approach to steady state seems to improve tolerability, as nausea is less frequent with EQW than EBID. EQW administrations may be associated with palpable skin nodules that generally resolve without further medical intervention. In comparative trials, EQW improved hemoglobin A1c more than EBID, sitagliptin, pioglitazone, or insulin glargine and reduced fasting plasma glucose more than EBID. Weight loss due to EQW or EBID was similar. EQW is the first glucose-lowering agent that is administered once weekly. |
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Authors:
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Mary Beth Deyoung; Leigh Macconell; Viren Sarin; Michael Trautmann; Paul Herbert |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-13 |
Journal Detail:
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Title: Diabetes technology & therapeutics Volume: - ISSN: 1557-8593 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-7-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100889084 Medline TA: Diabetes Technol Ther Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1 Amylin Pharmaceuticals, Inc. , San Diego, California. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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