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FDA Approves Once-Daily JANUVIA(TM), the First and Only DPP-4 Inhibitor Available in the United States for Type 2 Diabetes



    Merck & Co., Inc., Whitehouse Station, N.J., U.S.A., which
    operates as Merck, Sharp & Dohme (MSD) in countries outside the U.S.,
    announced today that the U.S. Food and Drug Administration (FDA)
    approved JANUVIA(TM) (sitagliptin phosphate), the first and only DPP-4
    inhibitor available in the United States for the treatment of type 2
    diabetes. JANUVIA has been approved 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 is 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.

    JANUVIA enhances a natural body system to significantly lower
    elevated blood sugar

    JANUVIA belongs to a new breakthrough class of prescription
    medications called dipeptidyl peptidase-4 (DPP-4) inhibitors that
    improves blood sugar control in patients with type 2 diabetes. JANUVIA
    enhances a natural body system called the incretin system, which helps
    to regulate glucose by affecting the beta cells and alpha cells in the
    pancreas. Through DPP-4 inhibition, JANUVIA works only when blood
    sugar is elevated to address diminished insulin due to beta-cell
    dysfunction and uncontrolled production of glucose by the liver due to
    alpha-cell and beta-cell dysfunction.

    "Those patients who are unable to adequately manage their type 2
    diabetes with lifestyle changes, like healthy eating and increased
    physical exercise, and who require medications now have a new product
    to help regulate their blood sugar levels," said Edward S. Horton,
    M.D., director of clinical research, Joslin Diabetes Center and
    professor of medicine, Harvard Medical School, Boston.

    "JANUVIA underscores MSD's commitment to the field of diabetes,
    and the benefits we strive to bring to patients and physicians who
    struggle in the treatment of type 2 diabetes," said Richard T. Clark,
    president and chief executive officer, Merck & Co., Inc. "The approval
    of JANUVIA is a clear example of MSD's focus on developing innovative
    therapies to improve human health around the world."

    JANUVIA had an overall incidence of side effects comparable to
    placebo

    In clinical trials, JANUVIA demonstrated an overall incidence of
    side effects comparable to placebo. The most common side effects
    reported with JANUVIA (greater than or equal to 5 percent and higher
    than placebo) were stuffy or runny nose and sore throat, upper
    respiratory infection, and headache.

    JANUVIA provides powerful HBA1C(1) reductions as monotherapy

    In two double-blind, placebo-controlled studies of 24 weeks
    (n=473) and 18 weeks (n=296) in patients with mild to moderate
    baseline HBA1C levels (mean 8.0%; enrollment range 7.0% to 10.0%),
    JANUVIA 100 mg once-daily showed significant mean differences in HBA1C
    from placebo of -0.8% and -0.6%, respectively (p less than 0.001). As
    is typical in trials of agents to treat type 2 diabetes, mean response
    to JANUVIA in HBA1C lowering appears to be related to the degree of
    HBA1C elevation at baseline. In a pooled analysis of these two
    monotherapy studies, a pre-specified subgroup analysis showed that
    when patients were grouped by baseline HBA1C into those with mildly
    elevated HBA1C levels (less than 8%, n=411), moderately elevated HBA1C
    levels (greater than or equal to 8% to less than 9%, n=239) and the
    highest elevated HBA1C levels (greater than or equal to 9%, n=119),
    mean differences in HBA1C from placebo after 18 weeks were -0.6%,
    -0.7% and -1.4%, respectively (p less than 0.001 for treatment by
    subgroup interactions).

    JANUVIA has a significant and complementary effect when added to
    metformin or TZDs

    JANUVIA addresses two of the three key defects that cause poor
    glucose control: diminished insulin release due to beta-cell
    dysfunction and uncontrolled production of glucose by the liver due to
    alpha-cell and beta-cell dysfunction. By adding JANUVIA to the insulin
    sensitizers metformin or pioglitazone (a TZD), the three key defects
    of type 2 diabetes can be addressed: insulin resistance, beta-cell
    dysfunction (decreased insulin release), and alpha-cell dysfunction
    (unsuppressed hepatic glucose production).

    In separate 24-week studies of patients with type 2 diabetes who
    were inadequately controlled on either metformin or pioglitazone
    alone, JANUVIA 100 mg once daily provided a complementary effect.
    JANUVIA showed significant mean differences in HBA1C from placebo of
    -0.7% in the metformin add-on study (p less than 0.001) and -0.7% in
    the pioglitazone add-on study (p less than 0.001). In those same
    studies, the mean HBA1C reduction from baseline with JANUVIA was 0.7%
    from a mean baseline HBA1C of 8.0% and 0.9% from a mean baseline of
    8.1%, respectively.

    Approximately twice as many patients got to HBA1C goal of less
    than 7% with JANUVIA

    In the metformin add-on study, more than twice as many patients
    uncontrolled on metformin got to HBA1C goal of less than 7% when
    JANUVIA was added (47 percent with JANUVIA and metformin vs. 18
    percent for patients continuing on metformin alone) (p less than
    0.001). Similarly, in the pioglitazone add-on study, 45 percent of
    patients adding JANUVIA to their regimen reached the HBA1C goal of
    less than 7% compared with 23 percent who continued on pioglitazone
    alone (p less than 0.001).

    JANUVIA provides powerful HBA1C lowering through combined
    reductions of both PPG and FPG throughout the day

    JANUVIA has been demonstrated to provide a 24-hour glucose
    response at mealtime, between meals and overnight. In a 24-week,
    placebo-controlled study of patients uncontrolled on metformin, adding
    JANUVIA 100 mg once daily substantially reduced PPG (or post-meal
    glucose) levels by 51 mg/dL and FPG by 25 mg/dL compared to patients
    continuing on metformin alone (p less than 0.001).

    Treatment with JANUVIA was not associated with weight gain or
    increased risk of hypoglycemia

    JANUVIA once-daily was weight neutral compared to placebo in
    clinical trials. Mean body weight decreased 0.2 kg (vs. 1.1 kg
    decrease for placebo) and 0.7 kg (vs. 0.6 kg), respectively, in two
    24-week trials: one in patients taking JANUVIA as monotherapy (n=193)
    and one in combination with metformin (n=399). The overall incidence
    of hypoglycemia in patients treated with JANUVIA 100 mg was similar to
    placebo (1.2 percent vs. 0.9 percent, respectively) across the
    clinical program. The incidence of selected gastrointestinal adverse
    reactions in patients treated with JANUVIA was as follows: abdominal
    pain (JANUVIA, 2.3 percent; placebo, 2.1 percent), nausea (1.4
    percent, 0.6 percent), and diarrhea (3.0 percent, 2.3 percent).

    Glucose-dependent mechanism of action

    The novel mechanism of JANUVIA is glucose-dependent, responding to
    the presence of elevated glucose and resulting in the release of
    insulin and decrease of glucagon only when needed, thereby lowering
    the potential for hypoglycemia. By inhibiting the DPP-4 enzyme,
    JANUVIA significantly increases the levels of active incretin
    hormones, increasing the synthesis and release of insulin from the
    pancreatic beta cells and decreasing the release of glucagon from the
    pancreatic alpha cells.

    Indications and contraindications for JANUVIA

    JANUVIA is indicated, as an adjunct to diet and exercise, to
    improve glycemic control in patients with type 2 diabetes mellitus.
    JANUVIA is also indicated to improve glycemic control, in combination
    with metformin or a TZD, in patients with type 2 diabetes when the
    single agent alone plus diet and exercise do not provide adequate
    glycemic control. 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. There are no contraindications for
    JANUVIA.

    Selected cautionary information for JANUVIA

    Because JANUVIA is renally eliminated, and to achieve plasma
    concentrations of JANUVIA similar to those in patients with normal
    renal function, a dosage adjustment is recommended in patients with
    moderate renal insufficiency and in patients with severe renal
    insufficiency or with end-stage renal disease (ESRD) requiring
    hemodialysis or peritoneal dialysis. Safety and effectiveness of
    JANUVIA in pediatric patients have not been established. There are no
    adequate and well-controlled studies in pregnant women. JANUVIA should
    be used during pregnancy only if clearly needed. Caution should be
    exercised when JANUVIA is administered to a nursing woman.

    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 greater than or equal to
    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 ESRD patients requiring hemodialysis. For patients with
    moderate renal insufficiency (CrCl greater than or equal to 30 to less
    than 50 mL/min), the dose of JANUVIA is 50 mg once daily. For those
    with severe renal insufficiency (CrCl less than 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.

    Pricing and availability of JANUVIA

    The price of once-daily JANUVIA in the United States will be $4.86
    per tablet. JANUVIA will be broadly available in pharmacies in the
    United States in the near future.

    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, the insulin that the body produces may not work as
    well as it should, and/or the liver may release too much glucose.

    Nearly 21 million people in the United States (7 percent of the
    population) have diabetes, with type 2 accounting for 90-95 percent of
    cases. Approximately half of people diagnosed with type 2 diabetes
    have not achieved adequate control of their blood sugar levels.
    Patients with diabetes can develop heart disease, kidney disease,
    blindness, vascular or neurological problems that can lead to
    amputation and can suffer increased rates of mortality.

    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 worldwide number may exceed 350
    million by 2025. The American Diabetes Association recommends that
    patients with type 2 diabetes achieve a target HBA1C level of less
    than 7%, while the American Academy of Clinical Endocrinologists
    recommends a target HBA1C level of less than 6.5%.

    Expanding clinical development program for JANUVIA

    MSD'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 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 Merck & Co., Inc.

    Merck & Co., Inc. which operates as Merck, Sharp & Dohme (MSD) in
    countries outside the U.S., 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.

    Forward-looking statement

    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. MSD 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 MSD's business, particularly those mentioned in the cautionary
    statements in Item 1 of MSD'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.

    NOTE: The views stated herein are those of Dr. Edward Horton and
    do not necessarily represent the views of Joslin Diabetes Center.
    Joslin Diabetes Center does not endorse products, did not participate
    in any tests for the product JANUVIA and makes no representations as
    to its quality or efficacy.

    JANUVIA(TM) is a registered trademark of Merck & Co., Inc.,
    Whitehouse Station, N.J., U.S.A., known as Merck, Sharp & Dohme
    outside the U.S.A.

    (1) HBA1C is a measure of a person's average blood glucose over a
    two- to three-month period.