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High interest in inhibitors of
the novel target sodium-dependent glucose (co-) transporter (SGLT) for therapy
of type 2 diabetes
Barcelona, January 23, 2006:
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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