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High interest in inhibitors of the novel target sodium-dependent glucose (co-) transporter (SGLT) for therapy of type 2 diabetes

 
  January, 23 2006 13:59
your information resource in human molecular genetics
 
     
A plethora of SGLT inhibitors in the patent literature and seven compounds in early clinical development indicate an abundance of interest in the therapeutic use of SGLT inhibitors for the treatment of type 2 diabetes. SGLT inhibitors do not intervene with glucose metabolism, thus being complementary to mainstream approaches to glucose regulation, i.e. PPAR agonists, DPP-IV antagonists and GLP-1 analogues. While SGLT-2 inhibitors block the reabsorption of glucose from the renal filtrate, SGLT1 inhibitors suppress absorption of glucose from the gut. Most of the known SGLT inhibitors are selective for SGLT2, but there are also mixed type inhibitors and SGLT1 inhibitors. Among the leading companies with clinical stage SGLT inhibitors are Sanofi-Aventis (AVE2268), GlaxoSmithKline (869682) and Bristol-Myers Squibb. These results were found in a search conducted by La Merie Business Intelligence. The results were published in the January 23 issue of R&D Pipeline News , edited by La Merie Business Intelligence.

SGLT2 is a molecular target to directly induce glucose excretion and to safely normalise plasma glucose in the treatment of type 2 diabetes. Chemically, most of the SGLT2 inhibitors are derived from the prototype phlorizin and structurally are glycosides. Exceptions are the second generation antisense approach from ISIS Pharmaceuticals and SGLT peptide antagonists from Theratech, both in preclinical stages. Japanese companies have pioneered the SGLT inhibitor arena (Tanabe Seiyaku with T-1095) and are still dominating the patent application field. SGLT2 inhibitors are also promising for other therapeutic uses such as obesity as they cause the net loss of calories from the body in form of glucose. In fact, GSK’s lead compound 869682 is under clinical investigation in obesity.

So far, little is known about the therapeutic efficacy of SGLT inhibitors due to the early development stage in the clinic. Theoretical safety concerns about increased glucosuria by SGLT2 inhibtion do not appear to be relevant as patients with familial renal glucosuria by an inherited defective form of SGLT2 have normal kidney function, are not hypoglycemic and have no pathology caused by the transporter defect.

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 the website, www.lamerie.com.


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