This site complies with the HONcode standard for trustworthy health information:
verify here.

Rewarding for
you and us
Defeat Diabetes Foundation

Defeat Diabetes
Foundation
150 153rd Ave,
Suite 300
Madeira Beach, FL 33708

Significant Glucose-Lowering Efficacy Of JANUVIA™ in Phase III Study

Posted: Thursday, September 21, 2006

New data presented for the first time at the 42nd annual meeting of the European Association for the Study of Diabetes (EASD) in Copenhagen demonstrated a mean reduction in A1C of 2.1% from a mean baseline A1C of 8.8% and a reduction of 2.9% for those with a mean A1c of 11.2%.

Using JANUVIA™ (sitagliptin phosphate) 50 mg twice daily and metformin 1000 mg twice daily, in patients off therapy at randomization. This study included another arm with JANUVIA and a lower dose of metformin and also monotherapy and placebo arms, and full results will be presented later this year. JANUVIA is Merck & Co., Inc.'s investigational oral medicine for type 2 diabetes.

In the clinical program as a whole, JANUVIA had an overall incidence of side effects comparable to placebo and was generally well tolerated. The most common side effects reported with JANUVIA (>3 percent and higher than placebo) were stuffy or runny nose and sore throat; headache; diarrhea; upper respiratory infection; joint pain; and urinary tract infection (with differences ranging from 0.1 percent to 1.5 percent vs. placebo).

In other Phase III studies, JANUVIA was administered once daily as monotherapy or add-on treatment. In an arm of this new study, JANUVIA was administered 50 mg twice daily simultaneously with metformin 1000 mg twice daily. In patients with moderately elevated baseline A1C levels (mean: 8.8%), simultaneous treatment of JANUVIA and metformin showed significant mean placebo-subtracted reductions in A1C of 2.1% (primary analysis, p<0.001). In addition, treatment with JANUVIA and metformin led to two-thirds of patients achieving goal A1C levels of <7% (66 percent) compared to patients on metformin alone (38 percent).

Significant A1C placebo-subtracted reductions (1.6%, p<0.001) and goal attainment (43 percent vs. 23 percent, p<0.001) also were seen with JANUVIA 50 mg twice daily when combined with a lower dose of metformin (500 mg twice daily).

This 24-week, randomized, double-blind, placebo-controlled study evaluated simultaneous treatment of JANUVIA with metformin and the use of both agents as monotherapy in 1,056 untreated patients with type 2 diabetes. Analyses were performed in patients who received JANUVIA 100 mg once daily (n=175), metformin 500 mg twice daily (n=178), metformin 1000 mg twice daily (n=177), JANUVIA 50 mg twice daily and metformin 500 mg twice daily (n=183), JANUVIA 50 mg twice daily and metformin 1000 mg twice daily (n=178), and placebo (n=165).

Though not included in the analysis that addressed the study hypotheses due to the severity of their hyperglycemia, an additional 117 patients with severely elevated baseline A1C (mean: 11.2%) were enrolled as an open label cohort receiving JANUVIA 50 mg twice daily and metformin 1000 mg twice daily. In this open label cohort, simultaneous treatment of JANUVIA with metformin showed a significant mean reduction in A1C from baseline of 2.9%.

"The significant glucose-lowering efficacy seen in this study suggests complementary mechanisms of action of sitagliptin and metformin resulting in an additive effect when both agents are given together," said Barry J. Goldstein, M.D., study investigator and director, Division of Endocrinology, Diabetes and Metabolic Diseases, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. "These results demonstrated that giving sitagliptin and metformin together was well tolerated with significantly greater efficacy than metformin alone, a mainstay of current diabetes treatment."

JANUVIA is an investigational once-daily medicine that, if approved, would potentially be the first in a new class of oral drugs (dipeptidyl peptidase-4 [DPP-4] inhibitors) in the U.S. that enhance the body's natural ability to lower blood sugar (glucose) when it is elevated. The mechanism of action of DPP-4 inhibitors is distinct from that of any currently available class of glucose-lowering agents.

Merck's clinical development program for JANUVIA is robust and continues to expand with 43 studies completed or under way, and four more studies set to begin this year. There are about 6,700 patients in the Company's clinical studies with about 4,700 of these patients being treated with JANUVIA. Additionally, about 1,100 patients have been treated with JANUVIA for more than a year.

JANUVIA is Merck's investigational oral, once daily DPP-4 inhibitor for the treatment of type 2 diabetes. JANUVIA is a potent and highly selective DPP-4 inhibitor. DPP-4 inhibitors work by enhancing a natural body system that lowers blood sugar, the incretin system. When blood sugar is elevated, incretins work in two ways to help the body regulate high blood sugar levels: they trigger the pancreas to increase insulin and signal the liver to reduce glucose production. DPP-4 inhibitors enhance the body's own ability to control blood sugar levels by increasing the active levels of these incretin hormones in the body, helping to decrease blood sugar levels in patients with type 2 diabetes. The mechanism of action is distinct from any existing class of glucose lowering agents.

JANUVIA has been accepted for standard review by the U.S. Food and Drug Administration (FDA). Merck expects an FDA action on the New Drug Application (NDA) by mid-October. The Company is also moving forward as planned with filings in countries outside the United States. JANUVIA became the first marketed DPP-4 inhibitor in the world when it received regulatory approval from Mexico in August.

JANUVIA also is being investigated as part of a single tablet combination with metformin (MK-0431A). MK-0431A has been accepted for standard review by the FDA, and an FDA action is expected by the end of March 2007. Regulatory filings in countries outside the United States are moving forward as planned.

Source: Diabetes In Control: Presented in Copenhagen last Saturday at the 42nd annual meeting of the European Association for the Study of Diabetes.