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Feature

Dosing convenience mandates the pipeline of glucagon-like peptide-1 (GLP-1) analogs for type 2 diabetes

Posted on: 06 Feb 06
Dosing convenience mandates the pipeline of glucagon-like peptide-1 (GLP-1) analogs for type 2 diabetes

Summary

Twice-daily injection is the benchmark set by exenatide, the first GLP-1 analog launched in the US by Lilly in June 2005 and half-year sales of US$ 74.6 mln, which now faces competition by GLP-1 analog treatment modalities with less frequent dosing.

Barcelona, Spain | Feb 6, 2006 | The Business Intelligence firm La Merie S.L. reported today that twice-daily injection is the benchmark set by exenatide, the first GLP-1 analog launched in the US by Lilly in June 2005 and half-year sales of US$ 74.6 mln, which now faces competition by GLP-1 analog treatment modalities with less frequent dosing. More convenience is brought to patients with once-daily dosing from the closest competitor (Novo Nordisk) which Lilly counters with a once-a-week injectable drug delivery. Other competitors follow with sustained release formulations of GLP-1 analogs or develop a nasal spray GLP-1 analog as a non-invasive alternative to injections. Another, yet IND or preclinical stage approach is the development of fusion proteins of GLP-1 with large carrier proteins such as albumin or transferrin leading to even longer half-lives, thus potentially allowing dosing every 2 or 3 weeks. These results were found in a search conducted by La Merie Business Intelligence published in the February 6 issue of R&D Pipeline News, edited by La Merie, and can be acquired as a Project Pipeline List at www.pipelinereview.com.


 


Both enzymatic cleavage and renal clearance contribute to a very short circulating half-life of several minutes for native GLP-1 which is a 30-amino acid gut peptide produced in enteroendocrine cells located in the distal ileum and colon. Thus, GLP-1 analogs have been constructed with resistance to enzymatic cleavage. These GLP-1 mimetics bind to GLP-1 receptors with similar affinity and produce biological actions identical to those of native GLP-1 which controls blood glucose via multiple actions including stimulation of insulin secretion and inhibition of both glucagon secretion and gastric emptying. Preclinical data suggest that GLP-1 analogs engage signaling pathways in the islet beta-cell that lead to stimulation of beta-cell replication and inhibition of beta-cell apoptosis. However, it remains to be proven clinically whether GLP1 analogs may reverse the decline in beta-cell mass of the pancreas that is characteristic of the natural history of type 2 diabetes.


 


Exenatide from Lilly is approved for use in patients with type 2 diabetes who exhibit unaceptable glycemic control whil using meformin and/or sulfonylurea. GLP-1 analog therapy clinically has shown the advantage of reducing body weight, but is associated with nausea and vomiting as the most common adverse effects which might be reduced with optimized dosing regimens.


 


Apart from use of GLP-1 analogs in the treatment of diabetes, its usefulness currently is being investigated in clinical studies of irritable bowel syndrome and functional dyspepsia. Further studies explore the effects of natural GLP-1 and of AC2592 from Amylin Pharmaceuticals administered by continuous infusion in patients with congestive heart failure.


 


 



About La Merie


 


La Merie S.L. is a Business Intelligence enterprise fully dedicated to provide high quality R&D information to the biopharmaceutical industry. La Merie offers individual consultancy services and publishes reports and periodicals. For more information visit www.lamerie.com.


 



 


About R&D Pipeline News


 


R&D Pipeline News is a premier information source about research and development projects in the pipeline of the biopharmaceutical industry and is directed to all stakeholders in R&D. The weekly publication comes in a rapid- and easy-to-screen tabular format and provides access to the original information source via hyperlinks. R&D Pipeline News covers all relevant treatment modalities and is directly delivered to the desktop via e-mail.


 


More information about the journal, a free trial and subscriptions are available via La Merie’s Business Intelligence Center www.pipelinereview.com.

La Merie Business Intelligence

Last updated on: 27/08/2010 11:40:18

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