Merck’s Omarigliptin, an Investigational Once-Weekly DPP-4 Inhibitor, Achieved Similar A1C Reductions to JANUVIA® (sitagliptin) in Patients with Type 2 Diabetes Inadequately Controlled on Metformin Monotherapy


September 16, 2015 9:16 am ET

Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced that omarigliptin, Merck’s investigational once-weekly
DPP-4 inhibitor in development for adults with type 2 diabetes, achieved
its primary efficacy endpoint in a Phase 3 study. Omarigliptin was found
to be non-inferior to Merck’s once-daily DPP-4 inhibitor, JANUVIA®
(sitagliptin), at reducing patients’ A1C* levels
from baseline, with similar A1C reductions achieved in both groups. The
head-to-head study was designed to evaluate once-weekly treatment with
omarigliptin 25 mg compared to 100 mg of JANUVIA once daily, a widely
prescribed DPP-4 inhibitor worldwide. Results were presented during an
oral session at the 51st European Association for the Study
of Diabetes (EASD) Annual Meeting.

“Type 2 diabetes is a chronic, progressive disease that affects millions
of Americans2, and its prevalence continues to grow rapidly.
Many people are still not at their recommended blood sugar levels,
underscoring the importance of individualized blood sugar goals and
multiple treatment options,” said Sam Engel, M.D., associate vice
president, Merck clinical research, diabetes and endocrinology.
“Omarigliptin has the potential to be an important treatment option,
particularly for those who also prefer once-weekly dosing.”

Merck submitted a new drug application to the Japanese Pharmaceuticals
and Medical Devices Agency in November 2014 and plans to submit for
regulatory approval of omarigliptin in the U.S. by the end of 2015. The
clinical development program for omarigliptin, O-QWEST (Omarigliptin
Q Weekly Efficacy and Safety in Type 2
Diabetes), includes 10 Phase 3 clinical trials involving approximately
8,000 patients with type 2 diabetes.

About the study

This Phase 3 randomized, double-blind, non-inferiority trial assessed
the efficacy, safety and tolerability of omarigliptin 25 mg once weekly
compared to JANUVIA 100 mg once daily in adults with type 2 diabetes
(n=642) who experienced inadequate glycemic control while taking
metformin. The primary efficacy endpoint was non-inferiority of
omarigliptin to JANUVIA in decreasing A1C levels from baseline to week
24.1 At the start of the trial, baseline A1C was
approximately 7.5 percent in both groups. Mean baseline fasting plasma
glucose (FPG) levels were also similar between treatment groups.

The study achieved its primary efficacy endpoint of non-inferior
reductions in A1C for omarigliptin compared to JANUVIA at 24 weeks.1
At week 24, patients taking omarigliptin had an average A1C reduction
from baseline of -0.47 percent as compared to an average reduction of
-0.43 percent among patients taking JANUVIA, with a difference of -0.03
between groups (95% CI [-0.15, 0.08]). In patients in the pre-specified
sub-group with a higher baseline A1C of greater than or equal to 8.0
percent, omarigliptin treatment resulted in reductions of -0.79 percent
compared to -0.71 percent for JANUVIA (difference = -0.08 percent; 95%
CI [-0.37, 0.21]).

The percentage of patients achieving their A1C goals was similar for
both omarigliptin and JANUVIA. At 24 weeks, 51 percent of patients
treated with omarigliptin reached an A1C of less than 7.0 percent,
compared to 49 percent of patients treated with JANUVIA (p=0.334). The
percentage of patients reaching an A1C of less than 6.5 percent was also
similar across treatment groups: 27 percent for omarigliptin compared
with 23 percent for JANUVIA (p=0.219). FPG was reduced from baseline by
0.8 mmol/L in the omarigliptin group and 0.5 mmol/L in the JANUVIA
group, with a between-group difference of -0.2 mmol/L (p= 0.089).1

The incidences of serious adverse events, drug-related adverse events
and discontinuations were similar across both treatment groups. Common
adverse events included diarrhea (0.9 percent for omarigliptin vs. 2.8
percent for JANUVIA), influenza (0.3 percent for omarigliptin vs. 2.2
percent for JANUVIA), upper respiratory tract infection (4.0 percent for
omarigliptin vs. 3.8 percent for JANUVIA), urinary tract infection (1.2
percent for omarigliptin vs. 2.8 percent for JANUVIA), lipase increase
(2.5 percent for omarigliptin vs. 4.1 percent for JANUVIA) and back pain
(2.5 percent for omarigliptin vs. 0.6 percent for JANUVIA). Adverse
events of hypoglycemia (symptomatic and asymptomatic) were reported in
3.7 percent of the omarigliptin group (with one severe hypoglycemia
event reported) and 4.7 percent of the JANUVIA group.1

Indications and Limitations of Use for JANUVIA®
(sitagliptin) 25 mg, 50 mg and 100 mg tablets

JANUVIA is indicated as an adjunct to diet and exercise to improve
glycemic control in adults with type 2 diabetes mellitus. JANUVIA should
not be used in patients with type 1 diabetes or for the treatment of
diabetic ketoacidosis. JANUVIA has not been studied in patients with a
history of pancreatitis. It is unknown whether patients with a history
of pancreatitis are at increased risk of developing pancreatitis while
taking JANUVIA.

Selected Important Risk Information about JANUVIA

JANUVIA is contraindicated in patients with a history of a serious
hypersensitivity reaction to sitagliptin, such as anaphylaxis or

There have been postmarketing reports of acute pancreatitis, including
fatal and nonfatal hemorrhagic or necrotizing pancreatitis, in patients
taking JANUVIA. After initiating JANUVIA, observe patients carefully for
signs and symptoms of pancreatitis. If pancreatitis is suspected,
promptly discontinue JANUVIA and initiate appropriate management. It is
unknown whether patients with a history of pancreatitis are at increased
risk of developing pancreatitis while taking JANUVIA.

Assessment of renal function is recommended prior to initiating JANUVIA
and periodically thereafter. A dosage adjustment is recommended in
patients with moderate or severe renal insufficiency and in patients
with end-stage renal disease requiring hemodialysis or peritoneal
dialysis. Caution should be used to ensure that the correct dose of
JANUVIA is prescribed.

There have been postmarketing reports of worsening renal function,
including acute renal failure, sometimes requiring dialysis. A subset of
these reports involved patients with renal insufficiency, some of whom
were prescribed inappropriate doses of sitagliptin.

When JANUVIA was used in combination with a sulfonylurea or insulin,
medications known to cause hypoglycemia, the incidence of hypoglycemia
was increased over that of placebo. Therefore, a lower dose of
sulfonylurea or insulin may be required to reduce the risk of

The incidence (and rate) of hypoglycemia based on all reports of
symptomatic hypoglycemia were: 12.2% (0.59 episodes/patient-year) for
JANUVIA 100 mg in combination with glimepiride (with or without
metformin), 1.8% (0.24 episodes/patient-year) for placebo in combination
with glimepiride (with or without metformin), 15.5% (1.06
episodes/patient-year) for JANUVIA 100 mg in combination with insulin
(with or without metformin), and 7.8% (0.51 episodes/patient-year) for
placebo in combination with insulin (with or without metformin).

There have been postmarketing reports of serious hypersensitivity
reactions in patients treated with JANUVIA, such as anaphylaxis,
angioedema, and exfoliative skin conditions including Stevens -Johnson
syndrome. Onset of these reactions occurred within the first 3 months
after initiation of treatment with JANUVIA, with some reports occurring
after the first dose. If a hypersensitivity reaction is suspected,
discontinue JANUVIA, assess for other potential causes for the event,
and institute alternative treatment for diabetes.

Angioedema has also been reported with other dipeptidyl peptidase-4
(DPP-4) inhibitors. Use caution in a patient with a history of
angioedema with another DPP-4 inhibitor because it is unknown whether
such patients will be predisposed to angioedema with JANUVIA.

There have been postmarketing reports of severe and disabling arthralgia
in patients taking DPP-4 inhibitors. The time to onset of symptoms
following initiation of drug therapy varied from 1 day to years.
Patients experienced relief of symptoms upon discontinuation of the
medication. A subset of patients experienced a recurrence of symptoms
when restarting the same drug or a different DPP-4 inhibitor. Consider
DPP-4 inhibitors as a possible cause for severe joint pain and
discontinue drug if appropriate.

There have been no clinical studies establishing conclusive evidence of
macrovascular risk reduction with JANUVIA or with any other antidiabetic

In clinical studies, the adverse reactions reported, regardless of
investigator assessment of causality, in ≥5% of patients treated with
JANUVIA as monotherapy and in combination therapy and more commonly than
in patients treated with placebo, were upper respiratory tract
infection, nasopharyngitis, and headache.

Merck commitment to diabetes

At Merck, we are committed to improving type 2 diabetes care through
scientific advancement and innovation for the millions of people living
with diabetes every day. We strive to deliver a broad range of
treatments and educational tools for patients and healthcare providers
and are applying significant resources and capabilities with a continued
focus on research and development.

About Merck

Today’s Merck is a global healthcare leader working to help the world be
well. Merck is known as Merck outside the United States and Canada.
Through our prescription medicines, vaccines, biologic therapies, and
animal health products, we work with customers and operate in more than
140 countries to deliver innovative health solutions. We also
demonstrate our commitment to increasing access to healthcare through
far-reaching policies, programs and partnerships. For more information,
and connect with us on Twitter,
and YouTube.

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

This news release of Merck & Co., Inc., Kenilworth, NJ, USA (the
“company”) includes “forward-looking statements” within the meaning of
the safe harbor provisions of the United States Private Securities
Litigation Reform Act of 1995. These statements are based upon the
current beliefs and expectations of the Company’s management and are
subject to significant risks and uncertainties. There can be no
guarantees with respect to pipeline products that the products will
receive the necessary regulatory approvals or that they will prove to be
commercially successful. If underlying assumptions prove inaccurate or
risks or uncertainties materialize, actual results may differ materially
from those set forth in the forward-looking statements.

Risks and uncertainties include, but are not limited to, general
industry conditions and competition; general economic factors, including
interest rate and currency exchange rate fluctuations; the impact of
pharmaceutical industry regulation and healthcare legislation in the
United States and internationally; global trends toward healthcare cost
containment; technological advances, new products and patents attained
by competitors; challenges inherent in new product development,
including obtaining regulatory approval; the Company’s ability to
accurately predict future market conditions; manufacturing difficulties
or delays; financial instability of international economies and
sovereign risk; dependence on the effectiveness of the Company’s s
patents and other protections for innovative products; and the exposure
to litigation, including patent litigation, and/or regulatory actions.

The Company undertakes no obligation to publicly update any
forward-looking statement, whether as a result of new information,
future events or otherwise. Additional factors that could cause results
to differ materially from those described in the forward-looking
statements can be found in the Company’s 2014 Annual Report on Form 10-K
and the company’s other filings with the Securities and Exchange
Commission (SEC) available at the SEC’s Internet site (

Please see Prescribing Information for JANUVIA® (sitagliptin)
and Medication Guide for JANUVIA at


1 Gantz, I et al. Omarigliptin, a once-weekly DPP-4
inhibitor, provides similar glycaemic control to sitagliptin in patients
with type 2 diabetes mellitus inadequately controlled on metformin.
Presentation #110, to be presented at the 51st EASD Annual Meeting on
Sept. 16, 2015. Available at–2.

2 Centers for Disease Control and Prevention. National
Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the
United States, 2014. Atlanta, GA: US Department of Health and Human
Services; 2014;1–9.

* A1C is an estimate of a person’s average blood glucose over
a two- to three-month period.

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