Galvus, a new antidiabetic drug that appears to limit the weight gain and fluid retention which often occurs with other antidiabetic drugs, has been filed in the EU for the treatment of patients with type 2 diabetes, after being accepted for US regulatory review earlier this year.

The drug is the first in a new class of oral antidiabetic agents known as dipetidyl peptidase inhibitors (DDP-4) or incretin enhancers. Patients with type 2 diabetes have impaired incretin function and are unable to properly regulate their blood sugar levels.

Galvus works by inhibiting DPP-4; an enzyme that breaks down the glucagon-like peptide (GLP-1), by delaying the degradation of GLP-1, In this way, it extends the action of insulin  while also suppressing the release of glucagon.

Phase III trials show that when Galvus (vildaglipin) is taken together with Actos (piogliyazone), it lowers blood sugar levels by nearly 2% in patients with poor glycaemic control.  Actos is an insulin sensitiser, which stimulates the transport of glucose into the cell.  

Novartis claims Galvus' mode of action is distinct from other existing antidiabetic medications, as apart from lowering blood sugar levels, it blocks the weight gain and fluid retention associated with other oral drugs for type 2 diabetes.

These new findings were presented at the 66th Scientific Sessions of the American Diabetes Association in Washington DC, where Dr James Shannon, Novartis Pharma AG's head of development, told delegates: "This new data underscores the significant efficacy and good tolerability that has been consistently observed in the robust Galvus clinical development programme."

The study showed the combination of Galvus and Eli Lilly/Takeda's Actos led to an overall 1.9% reduction in blood sugar levels and demonstrated no significant weight gain and lower fluid retention levels compared to Actos alone.

Dr Shannon emphasised:  "The magnitude of blood sugar level reductions seen with the combination of Galvus and Actos is encouraging for patients struggling to reach and maintain their blood sugar levels.

In on-going phase III trials Galvus is being studied as both monotherapy and in combination with other standard antidiabetic drugs. Its estimated peak sales are said to be in the region of $2,000 million.

Merck filed a similar DPP-4 inhibitor, Januvia, with the US regulator in February 2006 and claims its clinical trials also showed similar results to Galvus regarding weight gain in patients.

However, both drugs can expect intense scrutiny as the DPP-4 protein is closely related to the DPP-8 and DPP-9 proteins  both of which are associated with fatal toxicities in rats.

pharmafocus@wiley.co.uk