Healthcare Industry News: metformin
News Release - September 14, 2006
New Phase III Data Showed Significant Glucose-Lowering Efficacy of JANUVIA(TM), an Investigational Medicine for Type 2 Diabetes, When Taken Simultaneously with MetforminSimultaneous Treatment with JANUVIA and metformin Led to Significant Placebo-Subtracted Mean Reductions in A1C Levels of up to 2.1%
WHITEHOUSE STATION, N.J.--(HSMN NewsFeed)--Sept. 14, 2006--New data presented today for the first time at the 42nd annual meeting of the European Association for the Study of Diabetes (EASD) in Copenhagen demonstrated a significant mean placebo-subtracted reduction in A1C(1) of 2.1% from a mean baseline A1C of 8.8% (primary analysis of all patients treated, p less than 0.001) with JANUVIA(TM) (sitagliptin phosphate) 50 mg twice daily and metformin 1000 mg twice daily, a commonly used diabetes therapy, 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 this study, simultaneous treatment with JANUVIA and metformin was generally well tolerated and showed no meaningful differences in tolerability compared to metformin alone. Side effects of simultaneous treatment with JANUVIA 50 mg twice daily and metformin 1000 mg twice daily compared to metformin 1000 mg twice daily alone included diarrhea (9 percent vs. 10 percent, respectively), nausea (6 percent vs. 8 percent, respectively), abdominal pain/discomfort (3 percent vs. 5 percent, respectively) and vomiting (3 percent vs. 1 percent, respectively). 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 (greater than or equal to 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).
Efficacy and safety results from new co-administration study with metformin
In clinical studies, an important predictive factor of the magnitude of A1C reduction in response to anti-hyperglycemic therapy is a patient's A1C level at baseline.
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 less than 0.001). In addition, treatment with JANUVIA and metformin led to two-thirds of patients achieving goal A1C levels of less than 7% (66 percent) compared to patients on metformin alone (38 percent).
Significant A1C placebo-subtracted reductions (1.6%, p less than 0.001) and goal attainment (43 percent vs. 23 percent, p less than 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 commitment to diabetes
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.
Merck is committed to developing innovative therapies that offer advances in the treatment of serious diseases - including diabetes. As part of Merck's commitment to diabetes research and education, the Company continues to support EASD through unrestricted educational grants and other funding.
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.
About type 2 diabetes
Type 2 diabetes is a condition in which the body has elevated blood sugar or glucose. With type 2 diabetes, the body may not make enough insulin (which helps the body use glucose), the insulin that the body produces may not work as well as it should, or the body may make too much glucose. Patients with diabetes can develop heart disease, kidney disease, blindness, vascular or neurological problems that can lead to amputation and they can suffer increased mortality.
Nearly 21 million people in the United States, or seven percent of the population, have diabetes, with type 2 diabetes accounting for 90 to 95 percent of the cases. Approximately two-thirds of people diagnosed with type 2 diabetes have not achieved adequate control of their blood sugar levels (A1C less than seven percent as recommended by the American Diabetes Association). It is estimated that one in three Americans born in 2000 will develop diabetes sometime during their lifetime. There are currently more than 230 million people with diabetes worldwide, and if nothing is done to slow the epidemic, the number may exceed 350 million by 2025.
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com.
Unite for Diabetes
Merck is proud to be a platinum sponsor of the Unite for Diabetes campaign. The Unite for Diabetes Campaign aims to highlight the alarming rise of diabetes worldwide and to encourage government support for a United Nations resolution on diabetes. The International Diabetes Federation (IDF) is leading the local diabetes community in a concerted effort to secure the resolution on or around World Diabetes Day 2007 (November 14th).
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the cautionary statements in Item 1 of Merck's Form 10-K for the year ended Dec. 31, 2005, and in its periodic reports on Form 10-Q and Form 8-K, which the company incorporates by reference.
(1)A1C is a measure of a person's average blood glucose over a two- to three-month period.
JANUVIA(TM) is the proposed trademark for MK-0431 (sitagliptin phosphate).
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