JANUVIA is indicated in patients with type 2 diabetes to improve glycemic control in combination with metformin when diet and exercise plus metformin do not provide adequate glycemic control. For patients with type 2 diabetes in whom use of a PPAR-gamma agonist (i.e. a thiazolidinedione) is appropriate, JANUVIA is indicated in combination with the PPAR-gamma agonist when diet and exercise plus the PPAR-gamma agonist alone do not provide adequate glycemic control.
The adoption applies to all of the 27 countries that are members of the European Union (EU), including the United Kingdom, Germany, France, Italy and Spain, as well as Norway and Iceland (who follow European Medicines Evaluation Agency (EMEA) decisions). JANUVIA will be launched shortly in the EU countries. JANUVIA is now approved for use in 42 countries around the world including Mexico, the United States, and the Philippines.
In October 2006, the U.S. Food and Drug Administration (FDA) approved JANUVIA as monotherapy and as add-on therapy to either of two other types of oral diabetes medications, metformin or thiazolidinediones (TZDs), to improve blood sugar (glucose) control in patients with type 2 diabetes when diet and exercise are not enough. The recommended dose of JANUVIA is 100 mg once daily. JANUVIA should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings.
In clinical trials, JANUVIA demonstrated an overall incidence of side effects comparable to placebo. The most common side effects reported with JANUVIA (>5 percent and greater than placebo) were stuffy or runny nose and sore throat, upper respiratory infection, and headache. The incidence of selected gastrointestinal adverse reactions in patients treated with JANUVIA was as follows: abdominal pain (2.3 percent; placebo, 2.1 percent), nausea (1.4 percent; placebo, 0.6 percent) and diarrhea (3.0 percent; placebo, 2.3 percent).
JANUVIA is an oral, once-daily, selective DPP-4 inhibitor. DPP-4 inhibitors work by enhancing a natural body process 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 the release of insulin and signal the liver to reduce its production of glucose. 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. JANUVIA is currently approved in at least one country in the major regions around the world including Asia Pacific, Europe, the United States and Latin America.
Sitagliptin is also being investigated as part of Merck's single tablet combination with metformin, a widely prescribed medicine for type 2 diabetes. JANUMET is the trademark for the combination tablet. The mechanism of action of DPP-4 inhibitors is distinct from that of metformin and other drugs in the currently available classes of glucose-lowering agents. JANUMET has been accepted for standard review by the FDA. FDA action is expected on the New Drug Application by the end of March 2007. The Company is also moving forward with regulatory filings in countries outside the United States.
Dosing of JANUVIA
The recommended dose of JANUVIA is 100 mg once daily, with or without food, for all approved indications. No dosage adjustment is needed for patients with mild to moderate hepatic insufficiency or in patients with mild renal insufficiency (CrCl >50 mL/min). To achieve plasma concentrations of JANUVIA similar to those in patients with normal renal function, lower dosages are recommended in patients with moderate and severe renal insufficiency as well as in end-stage renal disease (ESRD) patients requiring hemodialysis. For patients with moderate renal insufficiency (CrCl >30 to <50 mL/min), the dose of JANUVIA is 50 mg once daily. For those with severe renal insufficiency (CrCl <30 mL/min) or with ESRD requiring dialysis, the dose of JANUVIA is 25 mg once daily. Because there is a need for dosage adjustment based upon renal function, assessment of renal function is recommended prior to initiation of JANUVIA and periodically thereafter.
Use in specific populations
JANUVIA should be used during pregnancy only if clearly needed. Caution should be exercised when JANUVIA is administered to a nursing woman. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in the elderly and it may be useful to assess renal function in these patients prior to initiating dosing and periodically thereafter.
Expanding clinical trial program for JANUVIA
Merck's clinical development program for sitagliptin is robust and continues to expand with 47 studies completed or underway, and nine more studies set to begin this year. There are more than 7,600 patients in the Company's clinical studies with about 4,700 of these patients being treated with sitagliptin. Additionally, about 1,900 patients have been treated with sitagliptin for more than a year.
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.