Merck Sharp & Dohme (MSD) today received a positive opinion from the
Committee for Medicinal Products for Human Use (CHMP) recommending
European approval for JanumetTM (sitagliptin/metformin, MSD), a new option for the treatment of type 2
diabetes. Sitagliptin/metformin delivers substantial glucose lowering
through a combination of sitagliptin, an incretin enhancer (DPP-4
inhibitor), and metformin, with a low risk of hypoglycaemia and weight
gain.1,2 Sitagliptin/metformin targets three
key defects of diabetes: insulin deficiency from pancreatic beta cells
insulin resistance, and overproduction of glucose by the liver.3,4,5
The CHMP, which reviews medicines for the European Commission (EC), has
recommended sitagliptin/metformin be approved to improve glycaemic
control in type 2 diabetes patients inadequately controlled on diet and
exercise plus their maximally tolerated dose of metformin alone or those
already being treated with the combination of sitagliptin and metformin.
Sitagliptin/metformin is also recommended for approval in combination
with a sulphonylurea (SU) as an adjunct to diet and exercise in patients
inadequately controlled on their maximal tolerated dose of metformin and
an SU. The decision will be applicable to the 27 countries that are
members of the EU, as well as Norway and Iceland. Marketing
authorisation is expected in within 67 days, assuming the EMEA adopts
the opinion of the CHMP.
Kamlesh Khunti, Professor of Primary Care Diabetes and Vascular
Medicine, University of Leicester said, "Many
patients remain poorly controlled on their existing oral combination
therapy. In order to effectively treat our patients with type 2
diabetes, we need simple and effective treatments that address glucose
control and common tolerability issues such as hypoglycaemia and weight
gain. The complementary mechanisms of action of sitagliptin and
metformin provide us with a further option to substantially improve
glucose control and are generally well tolerated."
The CHMP positive opinion was based on phase III data showing
significant reductions in blood sugar.* In a
30-week, placebo-controlled clinical study to evaluate at 18 and 30
weeks the safety and efficacy of the addition of sitagliptin 100 mg
once-daily to patients inadequately controlled ongoing metformin (n=190;
mean baseline HbA1c 9.2%), sitagliptin provided significant improvements
in HbA1c levels compared with placebo (p < 0.001). In this study, the mean placebo-adjusted HbA1c reduction was
-1.0% after prior metformin therapy at 18 and 30 weeks. In a subgroup of
patients with baseline HbA1c greater than or equal to 10%, the mean
placebo-adjusted reduction was -1.8% beyond metformin alone at week 18
and, due to improved response from the placebo group, was 1.4% at 30
weeks.1
In this 30-week study, the overall incidence of adverse reactions
considered as drug-related was similar in the two treatment groups.
There were no statistically significant differences between the two
treatment groups in the incidence of hypoglycaemia or in the incidence
of prespecified gastrointestinal adverse events (abdominal pain
diarrhea, nausea, vomiting). A small decrease in mean body weight of
0.5kg was seen in both groups.1
In a separate, 24-week, randomised, double-blind, placebo-controlled
study with 701 patients with mildly to moderately elevated HbA1c levels
(mean baseline 8.0%) inadequately controlled on metformin, patients
taking JANUMET (n=453) experienced significant additional mean
placebo-subtracted reductions in HbA1c of 0.7% beyond that achieved by
patients who continued on metformin alone (n=224) (p < 0.001).2
The CHMP also reviewed phase III clinical trial results supporting the
tolerability and efficacy of sitagliptin 100 mg once-daily in
combination with glimepiride (a sulphonylurea) alone or with glimepiride
plus metformin. Overall, the trial data showed that the addition of
sitagliptin significantly reduced HbA1c levels and fasting plasma
glucose levels, and was generally well tolerated.6
In the clinical trial in combination with a sulphonylurea (glimepiride)
plus metformin, sitagliptin demonstrated an overall incidence of adverse
reactions higher than that seen with placebo, in part related to a
higher incidence of hypoglycaemia with the treatment compared to placebo
(16.4% vs. 0.9%, respectively).6 A higher rate
of hypoglycaemia is commonly seen when antihyperglycaemic agents are
used in combination with sulphonylurea agents. When sitagliptin is used
in combination with a sulphonylurea, a lower dose of the sulphonylurea
may be considered to reduce the risk of hypoglycaemia.
Sitagliptin/metformin is not to be used in patients with moderate or
severe renal impairment or in patients with hepatic insufficiency.
Sitagliptin/metformin is contraindicated in patients with:
hypersensitivity to the active substances or to any of the excipients;
diabetic ketoacidosis, diabetic pre-coma; acute conditions with the
potential to alter renal function; acute or chronic disease which may
cause tissue hypoxia; acute alcohol intoxication, alcoholism; or who are
lactating.
Worldwide availability
There have been over four million prescriptions for sitagliptin and more
than 600,000 prescriptions for sitagliptin/metformin worldwide.7 Sitagliptin/metformin has received approval in 17 countries and
sitagliptin is approved in more than 70 countries and is available in
every region around the world. It is estimated that over 53 million
people in Europe have diabetes.8
About Merck & Co., Inc., of Whitehouse Station, N.J., U.S.A.
Merck & Co., Inc. which operates in many countries as Merck Sharp &
Dohme or MSD, is a global research-driven pharmaceutical company
dedicated to putting patients first. Established in 1891, the Company
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 programme
that not only donate its medicines but help deliver them to the people
who need them. Merck & Co., Inc. 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. 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 risk factors and
cautionary statements in Item 1A of Merck´s Form 10-K for the year ended
Dec. 31, 2007, and in any risk factors or cautionary statements
contained in the Company´s periodic reports on Form 10-Q or current
reports on Form 8-K, which the Company incorporates by reference.
1 Raz I, Chen Y,Wu M et al. Efficacy and safety
of sitagliptin added to ongoing metformin therapy in patients with type
2 diabetes. Current Medical Research and Opinion 2008, 24(2): 537-550.
2 Charbonnel B, Karasik A, Wu M et al. Efficacy
and Safety of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Added to
Ongoing Metformin Therapy in Patients With Type 2 Diabetes Inadequately
Controlled With Metformin Alone. Diabetes Care 2006, 29(12): 2638-2643.
3 Deacon C, Ahréns
B, Holst JJ. Inhibitors of dipeptidyl peptidase IV: a novel approach for
the prevention and treatment of Type 2 diabetes? Expert Opinion on
Investigational Drugs 2004, 13(9): 1091-1102.
4 Raz I, Hanefeld M, Xu L, et al. Efficacy and
safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as
monotherapy in patients with type 2 diabetes mellitus. Diabetologia
2006, 49: 2564"“2571.
5 Holst JJ and Deacon CF, Inhibition of the
Activity of Dipeptidyl-Peptidase IV as a Treatment for Type 2 diabetes.
Diabetes 1998, 47: 1663-1670.
6 Hermansen K, Kipnes M, Luo E et al. Efficacy
and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in
patients with type 2 diabetes mellitus inadequately controlled on
glimepiride alone or on glimepiride and metformin. Diabetes, Obesity and
Metabolism 2007, 9(5): 733-745.
7 IMS Health, NPA (TM) Weekly, TRxs, week-ending October 20, 2006 through week-ending March 21
2008.
8 International Diabetes Federation: Diabetes
Atlas, 3rd ed. 2006 Chapter 1, p.28.
* Clinical data referenced in this press
release for JANUMET were from studies including sitagliptin plus
metformin as separate tablets. A clinical bioequivalence study has
demonstrated the equivalence between JANUMET and sitagliptin plus
metformin as separate tablets.
JANUMET TM is a registered trademark of Merck &
Co., Inc., of Whitehouse St, NJ, USA known in many countries as Merck
Sharp & Dohme