High interest in inhibitors of the novel target sodium-dependent glucose (co-) transporter (SGLT) for therapy of type 2 diabetes
Released on = January 23, 2006, 4:41 am
Press Release Author = La Merie Business Intelligence
Industry = Biotech
Press Release Summary = 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.
Press Release Body = 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.
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