FDA Approves SGLT2 Inhibitor STEGLATRO™ (ertugliflozin) and Fixed-Dose Combination STEGLUJAN™ (ertugliflozin and sitagliptin) for Adults with Type 2 Diabetes

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December 22, 2017 7:00 am ET

Merck (NYSE:MRK), known as MSD outside the United States and Canada, and
Pfizer Inc. (NYSE:PFE), today announced that the U.S. Food and Drug
Administration (FDA) has approved STEGLATROTM (ertugliflozin)
tablets, an oral sodium-glucose cotransporter 2 (SGLT2) inhibitor, and
the fixed-dose combination STEGLUJAN™ (ertugliflozin and sitagliptin)
tablets.

STEGLATRO is indicated as an adjunct to diet and exercise to improve
glycemic control in adults with type 2 diabetes mellitus. STEGLUJAN is
indicated as an adjunct to diet and exercise to improve glycemic control
in adults with type 2 diabetes mellitus when treatment with both
ertugliflozin and sitagliptin is appropriate. STEGLATRO and STEGLUJAN
are not recommended in patients with type 1 diabetes mellitus or for the
treatment of diabetic ketoacidosis. STEGLUJAN 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 for the development
of pancreatitis while using STEGLUJAN. STEGLATRO and STEGLUJAN are
contraindicated in patients with severe renal impairment, end-stage
renal disease or on dialysis, or with a history of a serious
hypersensitivity reaction to ertugliflozin. STEGLUJAN is also
contraindicated in patients with a history of a serious hypersensitivity
reaction to sitagliptin (such as anaphylaxis or angioedema). Additional
safety information can be found below.

These FDA approvals are supported by seven Phase 3 studies of
approximately 4,800 patients. STEGLATRO was studied as monotherapy and
in combination with metformin and/or sitagliptin, as well as with
insulin and a sulfonylurea, in adults with type 2 diabetes and moderate
renal impairment. “In clinical trials, treatment with STEGLATRO resulted
in significant A1C reductions when used alone or in combination with
sitagliptin,” said Juan Pablo Frias, M.D., president and principal
investigator, National Research Institute, Los Angeles. “This is
important, as A1C-lowering is a key component of diabetes management,
and many of my adult patients may need multiple medications to help
manage their condition.”

“Merck welcomes the opportunity to provide adult patients with type 2
diabetes and their physicians these new medicines to help lower A1C,
building on over a decade of experience with our diabetes portfolio and
reflecting our continued commitment to diabetes research and patient
care,” said Keith Kaufman, M.D., vice president, global clinical
development and therapeutic area head for diabetes, endocrinology and
women’s health, Merck Research Laboratories.

Diabetes is a chronic, progressive disease affecting approximately 30
million Americans (90 to 95 percent have type 2 diabetes). About
one-third of adults with type 2 diabetes in the U.S. are not at their
A1C goal.

“There remains a need to help adults with type 2 diabetes improve their
glycemic control, and as the prevalence of the disease continues to
rise, we are pleased to offer additional treatment options to these
patients and the healthcare providers who treat them,” said James
Rusnak, M.D., Ph.D., senior vice president and chief development
officer, internal medicine, Pfizer Global Product Development.

One of the studies supporting the FDA approvals was VERTIS SITA2, a
26-week double-blind, placebo-controlled study. VERTIS SITA2 evaluated
STEGLATRO (ertugliflozin) compared to placebo in 463 patients with type
2 diabetes inadequately controlled (baseline A1C of 7.0-10.5%) on
background metformin (≥1,500 mg/day) and sitagliptin (100 mg/day).
Patients were randomized to STEGLATRO 5 mg, STEGLATRO 15 mg or placebo
administered once daily, in addition to continuation of background
metformin and sitagliptin therapy. In the study, STEGLATRO provided
significant additional A1C reductions on top of metformin plus
sitagliptin of 0.7 percent and 0.8 percent, respectively, for the 5 and
15 mg doses, compared with 0.2 percent for placebo (p<0.001, for both comparisons), which was the study’s primary endpoint.

In this study, STEGLATRO significantly reduced body weight by 6.6 pounds
with the 5 mg dose and 6.2 pounds with the 15 mg dose, on top of
metformin plus sitagliptin, compared with 2.2 pounds with placebo.
Baseline body weight was 193.1 pounds, 190.9 pounds and 190.6 pounds for
the 5 mg, 15 mg and placebo groups, respectively. The difference from
placebo was -4.2 pounds for STEGLATRO 5 mg (95% CI: -5.7, -2.9) and -4.0
pounds for STEGLATRO 15 mg (95% CI: -5.3, -2.6). STEGLATRO 5 mg and 15
mg were also associated with significant reductions in fasting plasma
glucose (25.7 mg/dL and 32.1 mg/dL, respectively, vs. 6.5 mg/dL for
placebo; p<0.001, for both comparisons). Baseline fasting plasma glucose levels were 167.7 mg/dL, 171.7 mg/dL and 169.6 mg/dL for the 5 mg, 15 mg and placebo groups, respectively. Significant reductions in systolic blood pressure were also observed for STEGLATRO (3.8 mmHg for 5 mg and 4.5 mmHg for 15 mg, vs. 0.2 mmHg for placebo). Baseline systolic blood pressure values were 132.1 mmHg, 131.6 mmHg and 130.2 mmHg for the 5 mg, 15 mg and placebo groups, respectively. For systolic blood pressure, the difference from placebo was -3.7 mmHg for STEGLATRO (ertugliflozin) 5 mg (95% CI: -6.1, -1.2) and -4.3 mmHg for STEGLATRO 15 mg (95% CI: -6.7, -1.9). STEGLATRO is not indicated for weight loss or hypertension.

STEGLATRO causes intravascular volume contraction. Symptomatic
hypotension may occur after initiating STEGLATRO, particularly in
patients with impaired renal function (estimated glomerular filtration
rate [eGFR] less than 60 mL/min/1.73 m2), elderly patients
(≥65 years), patients with low systolic blood pressure or patients on
diuretics. Before initiating STEGLATRO, volume status should be assessed
and corrected if indicated. Monitor for signs and symptoms after
initiating therapy. Additional safety information can be found below.

In addition to STEGLATRO and STEGLUJAN (ertugliflozin and sitagliptin),
the only fixed-dose combination of an SGLT2 inhibitor and the dipeptidyl
peptidase-4 (DPP-4) inhibitor sitagliptin, the FDA also approved the
fixed-dose combination SEGLUROMETTM
(ertugliflozin and
metformin hydrochloride). SEGLUROMET is indicated as an adjunct to diet
and exercise to improve glycemic control in adults with type 2 diabetes
mellitus who are not adequately controlled on a regimen containing
ertugliflozin or metformin, or in patients who are already treated with
both ertugliflozin and metformin. SEGLUROMET is not recommended in
patients with type 1 diabetes mellitus or for the treatment of diabetic
ketoacidosis. The labeling for SEGLUROMET contains a boxed warning for
lactic acidosis. SEGLUROMET is contraindicated in patients with severe
renal impairment, end-stage renal disease or on dialysis, acute or
chronic metabolic acidosis, including diabetic ketoacidosis, or a
history of a serious hypersensitivity reaction to SEGLUROMET,
ertugliflozin or metformin hydrochloride. Additional safety information
is found below.

STEGLATRO is available in 5 mg and 15 mg tablets. STEGLUJAN combines 5
mg or 15 mg of ertugliflozin with 100 mg of sitagliptin. SEGLUROMET
combines 2.5 mg or 7.5 mg of ertugliflozin with 500 mg or 1,000 mg of
metformin hydrochloride.

Merck-Pfizer Collaboration and Product Availability

In 2013, Merck and Pfizer announced that they entered into a worldwide
collaboration, except Japan, for the co-development and co-promotion of
ertugliflozin. The Merck sales force will exclusively promote STEGLATRO
and the two fixed-dose combination products in the United States. Merck
and Pfizer will share potential revenues and certain costs on a 60/40
percent basis, respectively, and Pfizer may be entitled to additional
milestone payments.

Merck has established a list price (Wholesale Acquisition Cost) of $8.94
per day for STEGLATRO, $17.45 per day for STEGLUJAN and $8.94 per day
for SEGLUROMET. Wholesale acquisition costs do not include discounts
that may be paid on the products. STEGLATRO (ertugliflozin) and STEGLUJAN
(ertugliflozin and sitagliptin) are expected to be available in
pharmacies in January 2018. SEGLUROMET (ertugliflozin and metformin
hydrochloride) is expected to be available in February 2018.

Selected Important Risk Information about STEGLATRO



(continued)

Ketoacidosis, a serious life-threatening condition requiring urgent
hospitalization, has been reported in patients with type 1 and type 2
diabetes receiving SGLT2 inhibitors including STEGLATRO. Some cases were
fatal. Assess patients with signs and symptoms of metabolic acidosis for
ketoacidosis, regardless of blood glucose level. If ketoacidosis is
suspected, STEGLATRO should be discontinued, patient should be
evaluated, and prompt treatment should be instituted. Before initiating
STEGLATRO, consider risk factors for ketoacidosis, including pancreatic
insulin deficiency from any cause, caloric restriction, and alcohol
abuse. In patients treated with STEGLATRO, consider monitoring for
ketoacidosis and temporarily discontinuing STEGLATRO in clinical
situations known to predispose to ketoacidosis (e.g., prolonged fasting
due to acute illness or surgery).

STEGLATRO causes intravascular volume contraction and can cause renal
impairment. There have been postmarketing reports of acute kidney
injury, some requiring hospitalization and dialysis, in patients
receiving SGLT2 inhibitors. Before initiating STEGLATRO, consider
factors that may predispose patients to acute kidney injury. Consider
temporarily discontinuing STEGLATRO in any setting of reduced oral
intake or fluid losses; monitor patients for signs and symptoms of acute
kidney injury. If acute kidney injury occurs, discontinue STEGLATRO
promptly and institute treatment.

STEGLATRO increases serum creatinine and decreases eGFR. Patients with
moderate renal impairment (eGFR 30 to less than 60 mL/min/1.73 m2)
may be more susceptible to these changes. Renal function abnormalities
can occur after initiating STEGLATRO. Renal function should be evaluated
prior to initiating STEGLATRO and periodically thereafter. Use of
STEGLATRO is not recommended when eGFR is persistently between 30 and
less than 60 mL/min/1.73 m2 and is contraindicated in
patients with an eGFR less than 30 mL/min/1.73 m2.

There have been postmarketing reports of serious urinary tract
infections, including urosepsis and pyelonephritis, requiring
hospitalization in patients receiving SGLT2 inhibitors. Cases of
pyelonephritis also have been reported in patients treated with
STEGLATRO in clinical trials. Treatment with SGLT2 inhibitors increases
the risk for urinary tract infections. Evaluate patients for signs and
symptoms of urinary tract infections and treat promptly, if indicated.

An increased risk for lower limb amputation has been observed in
clinical studies with another SGLT2 inhibitor. Across seven Phase 3
clinical trials with STEGLATRO, non-traumatic lower limb amputations
were reported in 1 (0.1%) patient in the comparator group, 3 (0.2%)
patients in the STEGLATRO 5 mg group, and 8 (0.5%) patients in the
STEGLATRO 15 mg group. A causal association between STEGLATRO
(ertugliflozin) and lower limb amputation has not been definitively
established. Before initiating STEGLATRO, consider factors that may
predispose patients to the need for amputations. Counsel patients about
the importance of routine preventative foot care. Monitor patients and
discontinue STEGLATRO if complications occur.

Insulin and insulin secretagogues (e.g., sulfonylurea) are known to
cause hypoglycemia. STEGLATRO may increase the risk of hypoglycemia when
used in combination with insulin and/or an insulin secretagogue.
Therefore, a lower dose of insulin or insulin secretagogue may be
required to minimize the risk of hypoglycemia when used in combination
with STEGLATRO.

STEGLATRO increases the risk of genital mycotic infections. Patients who
have a history of genital mycotic infections or who are uncircumcised
are more likely to develop genital mycotic infections. Monitor and treat
appropriately.

Dose-related increases in low-density lipoprotein cholesterol (LDL-C)
can occur with STEGLATRO. Monitor and treat as appropriate.

There have been no clinical studies establishing conclusive evidence of
macrovascular risk reduction with STEGLATRO.

The most common adverse reactions associated with STEGLATRO (incidence
≥5%) were female genital mycotic infections.

Selected Important Risk Information about STEGLUJAN



(ertugliflozin
and sitagliptin) (continued)

There have been postmarketing reports of acute pancreatitis, including
fatal and nonfatal hemorrhagic or necrotizing pancreatitis, in patients
taking sitagliptin. After initiating STEGLUJAN, patients should be
observed carefully for signs and symptoms of pancreatitis. If
pancreatitis is suspected, STEGLUJAN should promptly be discontinued and
appropriate management should be initiated. It is unknown whether
patients with a history of pancreatitis are at increased risk for the
development of pancreatitis while using STEGLUJAN.

Ertugliflozin causes intravascular volume contraction. Symptomatic
hypotension may occur after initiating STEGLUJAN, particularly in
patients with impaired renal function (eGFR less than 60 mL/min/1.73 m2),
elderly patients (≥65 years), in patients with low systolic blood
pressure, and in patients on diuretics. Before initiating STEGLUJAN,
volume status should be assessed and corrected if indicated. Monitor for
signs and symptoms after initiating therapy.

Ketoacidosis, a serious life-threatening condition requiring urgent
hospitalization, has been reported in patients with type 1 and type 2
diabetes receiving SGLT2 inhibitors, including STEGLUJAN. Some cases
were fatal. Assess patients with signs and symptoms of metabolic
acidosis for ketoacidosis, regardless of blood glucose level. If
ketoacidosis is suspected, STEGLUJAN should be discontinued, patient
should be evaluated, and prompt treatment should be instituted. Before
initiating STEGLUJAN (ertugliflozin and sitagliptin), consider
risk factors for ketoacidosis, including pancreatic insulin deficiency
from any cause, caloric restriction, and alcohol abuse. In patients
treated with STEGLUJAN, consider monitoring for ketoacidosis and
temporarily discontinuing STEGLUJAN in clinical situations known to
predispose to ketoacidosis (e.g., prolonged fasting due to acute illness
or surgery).

STEGLUJAN causes intravascular volume contraction and can cause renal
impairment. There have been postmarketing reports of acute kidney
injury, some requiring hospitalization and dialysis, in patients
receiving SGLT2 inhibitors. Before initiating STEGLUJAN, consider
factors that may predispose patients to acute kidney injury, including
hypovolemia, chronic renal insufficiency, congestive heart failure, and
concomitant medications. Consider temporarily discontinuing STEGLUJAN in
any setting of reduced oral intake or fluid losses; monitor patients for
signs and symptoms of acute kidney injury. If acute kidney injury
occurs, discontinue STEGLUJAN promptly and institute treatment.

Ertugliflozin increases serum creatinine and decreases eGFR. Patients
with moderate renal impairment (eGFR 30 to less than 60 mL/min/1.73 m2)
may be more susceptible to these changes. Renal function abnormalities
can occur. Renal function should be evaluated prior to initiating
STEGLUJAN and periodically thereafter. Use of STEGLUJAN is not
recommended when eGFR is persistently between 30 and less than 60
mL/min/1.73 m2 and is contraindicated in patients with an
eGFR less than 30 mL/min/1.73 m2.

Serious urinary tract infections, including urosepsis and
pyelonephritis, requiring hospitalization have been identified in
patients receiving SGLT2 inhibitors. Cases of pyelonephritis also have
been reported in ertugliflozin-treated patients in clinical trials.
Treatment with SGLT2 inhibitors increases the risk for urinary tract
infections. Evaluate patients for signs and symptoms of urinary tract
infections and treat promptly.

An increased risk for lower limb amputation has been observed in
clinical studies with another SGLT2 inhibitor. Across seven Phase 3
clinical trials with ertugliflozin, non-traumatic lower limb amputations
were reported in 1 (0.1%) patient in the comparator group, 3 (0.2%)
patients in the ertugliflozin 5 mg group, and 8 (0.5%) patients in the
ertugliflozin 15 mg group. A causal association between ertugliflozin
and lower limb amputation has not been definitively established. Before
initiating STEGLUJAN, consider factors that may predispose patients to
the need for amputations. Counsel patients about the importance of
routine preventative foot care. Monitor patients and discontinue
STEGLUJAN if complications occur.

An association between DPP-4 inhibitor treatment and heart failure has
been observed in cardiovascular outcomes trials for two other members of
the DPP-4 inhibitor class. These trials evaluated patients with type 2
diabetes mellitus and atherosclerotic cardiovascular disease. Consider
the risks and benefits of STEGLUJAN prior to initiating treatment in
patients at risk for heart failure, such as those with a prior history
of heart failure and a history of renal impairment, and observe these
patients for signs and symptoms of heart failure during therapy. Advise
patients to report any symptoms of heart failure. If heart failure
develops, evaluate and manage appropriately, and consider
discontinuation of STEGLUJAN (ertugliflozin and sitagliptin).

STEGLUJAN may increase the risk of hypoglycemia when combined with
insulin and/or an insulin secretagogue. Consider lowering the dose of
these agents when coadministered with STEGLUJAN.

Ertugliflozin increases the risk of genital mycotic infections,
particularly in patients with a history of these infections or who are
uncircumcised. Monitor and treat appropriately.

Serious hypersensitivity reactions (anaphylaxis, angioedema, and
exfoliative skin conditions including Stevens-Johnson syndrome) have
been reported in patients treated with sitagliptin. If a
hypersensitivity reaction is suspected, discontinue STEGLUJAN, assess
for other potential causes for the event, and institute alternative
treatment for diabetes. Angioedema has also been reported with other
DPP-4 inhibitors. Use caution in a patient with a history of angioedema
with another DPP-4 inhibitor.

Dose-related increases in LDL-C can occur with STEGLUJAN.

Severe and disabling arthralgia has been reported 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 medication. Consider DPP-4 inhibitors
as a possible cause for severe joint pain and discontinue drug if
appropriate.

Bullous pemphigoid requiring hospitalization has been reported with
DPP-4 inhibitor use. In reported cases, patients typically recovered
with topical or systemic immunosuppressive treatment and discontinuation
of the DPP-4 inhibitor. Tell patients to report any development of
blisters or erosions. If bullous pemphigoid is suspected, discontinue
STEGLUJAN and consider referral to a dermatologist.

There have been no clinical studies establishing conclusive evidence of
macrovascular risk reduction with STEGLUJAN.

The most common adverse reactions associated with ertugliflozin
(incidence ≥5%) were female genital mycotic infections. The most common
adverse reactions with sitagliptin (incidence ≥5%) were upper
respiratory tract infection, nasopharyngitis, and headache. In the
add-on to sulfonylurea and add-on to insulin studies, hypoglycemia was
more commonly reported in patients treated with sitagliptin.

Selected Important Risk Information about SEGLUROMET



(ertugliflozin
and metformin hydrochloride)

Postmarketing cases of metformin-associated lactic acidosis have
resulted in death, hypothermia, hypotension, and resistant
bradyarrhythmias. The onset of metformin-associated lactic acidosis is
often subtle, accompanied only by nonspecific symptoms such as malaise,
myalgias, respiratory distress, somnolence, and abdominal pain.
Metformin-associated lactic acidosis was characterized by elevated blood
lactate levels (>5 mmol/Liter), anion gap acidosis (without evidence of
ketonuria or ketonemia), an increased lactate/pyruvate ratio and
metformin plasma levels generally >5 mcg/mL.

Risk factors for metformin-associated lactic acidosis include renal
impairment, concomitant use of certain drugs (e.g., carbonic anhydrase
inhibitors such as topiramate), age 65 years old or greater, having a
radiological study with contrast, surgery and other procedures, hypoxic
states (e.g., acute congestive heart failure), excessive alcohol intake,
and hepatic impairment.

If metformin-associated lactic acidosis is suspected, immediately
discontinue SEGLUROMET (ertugliflozin and metformin hydrochloride) and
institute general supportive measures in a hospital setting. Prompt
hemodialysis is recommended.

Educate patients and their families about the symptoms of lactic
acidosis and, if these symptoms occur, instruct them to discontinue
SEGLUROMET and promptly notify their health care provider.

Recommendations to reduce the risk include:

  • Renal Impairment: Obtain an estimated eGFR prior to initiating therapy
    and annually or more frequently in patients at increased risk of
    developing renal impairment.
  • Drug Interactions: More frequent monitoring is recommended when
    administered with drugs that impair renal function, result in
    hemodynamic change, interfere with acid-base balance, or increase
    metformin accumulation.
  • Age 65 or Greater: Assess renal function more frequently.
  • Radiological Studies with Contrast: Stop SEGLUROMET at the time
    of, or prior to, an iodinated contrast imaging procedure in patients
    with an eGFR of less than 60 mL/min/1.73 m2; patients with
    a history of hepatic impairment, alcoholism, or heart failure; or
    patients who will be administered intra-arterial iodinated contrast.
    Re-evaluate eGFR 48 hours after the procedure and restart SEGLUROMET
    if renal function is stable.
  • Surgery and Other Procedures: Discontinue while patients have
    restricted food and fluid intake.
  • Hypoxic States: Discontinue in conditions associated with hypoxemia.
  • Excessive Alcohol Intake: Warn patients against excessive alcohol
    intake.
  • Hepatic Impairment: Avoid use in patients with evidence of hepatic
    disease.

Ertugliflozin causes intravascular volume contraction and symptomatic
hypotension may occur after initiating SEGLUROMET, particularly in
patients with impaired renal function (eGFR less than 60 mL/min/1.73 m2),
elderly patients (≥65 years), or patients on diuretics. Before
initiating SEGLUROMET (ertugliflozin and metformin hydrochloride),
assess and correct volume status. Monitor for hypotension.

Ketoacidosis, a serious life-threatening condition requiring urgent
hospitalization, has been reported in patients with type 1 and type 2
diabetes receiving SGLT2 inhibitors, including ertugliflozin. Some cases
were fatal. Assess patients with signs and symptoms of metabolic
acidosis for ketoacidosis, regardless of blood glucose level. If
ketoacidosis is suspected, SEGLUROMET should be discontinued, patient
should be evaluated, and prompt treatment should be instituted. Before
initiating SEGLUROMET, consider risk factors for ketoacidosis, including
pancreatic insulin deficiency from any cause, caloric restriction, and
alcohol abuse. In patients treated with SEGLUROMET, consider monitoring
for ketoacidosis and temporarily discontinuing SEGLUROMET in clinical
situations known to predispose to ketoacidosis (e.g., prolonged fasting
due to acute illness or surgery).

SEGLUROMET causes intravascular volume contraction and can cause renal
impairment. There have been reports of acute kidney injury, some
requiring hospitalization and dialysis, in patients receiving SGLT2
inhibitors. Before initiating SEGLUROMET, consider factors that may
predispose patients to acute kidney injury. Consider temporarily
discontinuing SEGLUROMET in any setting of reduced oral intake or fluid
losses; monitor patients for signs and symptoms of acute kidney injury.
If acute kidney injury occurs, discontinue SEGLUROMET promptly and
institute treatment.

SEGLUROMET increases serum creatinine and decreases eGFR. Patients with
moderate renal impairment (eGFR 30 to less than 60 mL/min/1.73 m2)
may be more susceptible to these changes. Renal function abnormalities
can occur after initiating SEGLUROMET. Renal function should be
evaluated prior to initiating SEGLUROMET and periodically thereafter.
Use of SEGLUROMET is not recommended when eGFR is persistently between
30 and less than 60 mL/min/1.73 m2 and is contraindicated in
patients with an eGFR less than 30 mL/min/1.73 m2.

There have been postmarketing reports of serious urinary tract
infections, including urosepsis and pyelonephritis, requiring
hospitalization in patients receiving SGLT2 inhibitors. Cases of
pyelonephritis also have been reported in ertugliflozin-treated patients
in clinical trials. Treatment with SGLT2 inhibitors increases the risk
for urinary tract infections. Evaluate for urinary tract infections and
treat promptly.

An increased risk for lower limb amputation has been observed in
clinical studies with another SGLT2 inhibitor. Across seven Phase 3
clinical trials with ertugliflozin, non-traumatic lower limb amputations
were reported in 1 (0.1%) patient in the comparator group, 3 (0.2%)
patients in the ertugliflozin 5 mg group, and 8 (0.5%) patients in the
ertugliflozin 15 mg group. A causal association between ertugliflozin
and lower limb amputation has not been definitively established. Before
initiating SEGLUROMET, consider factors that may predispose patients to
the need for amputations. Counsel patients about the importance of
routine preventative foot care. Monitor patients and discontinue
SEGLUROMET (ertugliflozin and metformin hydrochloride) if complications
occur.

Ertugliflozin may increase the risk of hypoglycemia when combined with
insulin and/or an insulin secretagogue. Consider lowering the dose of
these agents when coadministered with SEGLUROMET. Hypoglycemia could
occur when caloric intake is deficient, when strenuous exercise is not
compensated by caloric supplementation or during concomitant use of
other glucose-lowering agents or with the use of ethanol.

Ertugliflozin increases the risk of genital mycotic infections,
particularly in patients with a history of these infections or who are
uncircumcised. Monitor and treat appropriately.

Dose-related increases in LDL-C can occur with SEGLUROMET. Monitor and
treat as appropriate.

There have been no clinical studies establishing conclusive evidence of
macrovascular risk reduction with SEGLUROMET.

The most common adverse reactions associated with ertugliflozin
(incidence ≥5%) were female genital mycotic infections. The most common
adverse reactions associated with metformin (incidence ≥5%) were
diarrhea, nausea, vomiting, flatulence, abdominal discomfort,
indigestion, asthenia and headache.

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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
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Risks and uncertainties include but are not limited to, general industry
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Pfizer Disclosure Notice

The information contained in this release is current as of December 22,
2017. Pfizer assumes no obligation to update forward-looking statements
contained in this release as the result of new information or future
events or developments.

This release contains forward-looking information about STEGLATRO
(ertugliflozin), STEGLUJAN (ertugliflozin and sitagliptin) and
SEGLUROMET (ertugliflozin and metformin hydrochloride), including their
potential benefits, that involves substantial risks and uncertainties
that could cause actual results to differ materially from those
expressed or implied by such statements. Risks and uncertainties
include, among other things, uncertainties regarding the commercial
success of STEGLATRO, STEGLUJAN and SEGLUROMET; the uncertainties
inherent in research and development, including the ability to meet
anticipated clinical trial commencement and completion dates and
regulatory submission dates, as well as the possibility of unfavorable
clinical trial results, including unfavorable new clinical data and
additional analyses of existing clinical data; whether and when
applications for STEGLATRO, STEGLUJAN, and SEGLUROMET may be filed in
any other jurisdictions; whether and when any such other applications
for STEGLATRO, STEGLUJAN and SEGLUROMET that may be pending or filed may
be approved by regulatory authorities, which will depend on the
assessment by such regulatory authorities of the benefit-risk profile
suggested by the totality of the efficacy and safety information
submitted; decisions by regulatory authorities regarding labeling and
other matters that could affect the availability or commercial potential
of STEGLATRO, STEGLUJAN, and SEGLUROMET; and competitive developments.
The competitive landscape for type 2 diabetes therapies, including SGLT2
inhibitors, continues to evolve. The success of our ertugliflozin
program is dependent on developments in that space.

A further description of risks and uncertainties can be found in
Pfizer’s Annual Report on Form 10-K for the fiscal year ended December
31, 2016 and in its subsequent reports on Form 10-Q, including in the
sections thereof captioned “Risk Factors” and “Forward-Looking
Information and Factors That May Affect Future Results”, as well as in
its subsequent reports on Form 8-K, all of which are filed with the U.S.
Securities and Exchange Commission and available at
www.sec.gov


and www.pfizer.com.

Please see Prescribing Information for STEGLATRO at
http://www.merck.com/product/usa/pi_circulars/s/steglatro/steglatro_pi.pdf
and Patient Information for STEGLATRO at
http://www.merck.com/product/usa/pi_circulars/s/steglatro/steglatro_mg.pdf

Please see Prescribing Information for STEGLUJAN at
http://www.merck.com/product/usa/pi_circulars/s/steglujan/steglujan_pi.pdf
and Patient Information for STEGLUJAN at
http://www.merck.com/product/usa/pi_circulars/s/steglujan/steglujan_mg.pdf

Please see Prescribing Information for SEGLUROMET (ertugliflozin and
metformin hydrochloride)
at
http://www.merck.com/product/usa/pi_circulars/s/segluromet/segluromet_pi.pdf
and Patient Information for SEGLUROMET at
http://www.merck.com/product/usa/pi_circulars/s/segluromet/segluromet_mg.pdf



Merck
Media:
Pam Eisele, 267-305-3558
or
Kristen Drake, 908-334-4688
or
Investors:
Michael DeCarbo, 908-740-1807
or
Pfizer
Media:
Neha Wadhwa, 212-733-2835
or
Investors:
Ryan Crowe, 212-733-8160

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