Diabetes Pro Quarterly - Fall 2019 - 10

OZEMPIC ® (semaglutide) injection
Rx Only
BRIEF SUMMARY: Please consult package insert for full prescribing
information.
WARNING: RISK OF THYROID C-CELL TUMORS: In rodents, semaglutide
causes dose-dependent and treatment-duration-dependent thyroid
C-cell tumors at clinically relevant exposures. It is unknown whether
OZEMPIC ® causes thyroid C-cell tumors, including medullary thyroid
carcinoma (MTC), in humans as human relevance of semaglutideinduced rodent thyroid C-cell tumors has not been determined [see
Warnings and Precautions]. OZEMPIC® is contraindicated in patients
with a personal or family history of MTC or in patients with Multiple
Endocrine Neoplasia syndrome type 2 (MEN 2) [see Contraindications].
Counsel patients regarding the potential risk for MTC with the use
of OZEMPIC ® and inform them of symptoms of thyroid tumors (e.g.
a mass in the neck, dysphagia, dyspnea, persistent hoarseness).
Routine monitoring of serum calcitonin or using thyroid ultrasound is
of uncertain value for early detection of MTC in patients treated with
OZEMPIC ® [see Contraindications and Warnings and Precautions].
INDICATIONS AND USAGE: OZEMPIC® is indicated as an adjunct to diet and
exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Limitations of Use: OZEMPIC® is not recommended as a first-line therapy for patients
who have inadequate glycemic control on diet and exercise because of the uncertain
relevance of rodent C-cell tumor findings to humans [see Warnings and Precautions].
OZEMPIC® has not been studied in patients with a history of pancreatitis. Consider
other antidiabetic therapies in patients with a history of pancreatitis [see Warnings and
Precautions]. OZEMPIC® is not a substitute for insulin. OZEMPIC® is not indicated
for use in patients with type 1 diabetes mellitus or for the treatment of patients with
diabetic ketoacidosis, as it would not be effective in these settings.
CONTRAINDICATIONS: OZEMPIC® is contraindicated in patients with: A personal
or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple
Endocrine Neoplasia syndrome type 2 (MEN 2) [see Warnings and Precautions];
Known hypersensitivity to semaglutide or to any of the product components [see
Warnings and Precautions].
WARNINGS AND PRECAUTIONS: Risk of Thyroid C-Cell Tumors: In mice
and rats, semaglutide caused a dose-dependent and treatment-duration-dependent
increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after
lifetime exposure at clinically relevant plasma exposures. It is unknown whether
OZEMPIC® causes thyroid C-cell tumors, including medullary thyroid carcinoma
(MTC), in humans as human relevance of semaglutide-induced rodent thyroid
C-cell tumors has not been determined. Cases of MTC in patients treated with
liraglutide, another GLP-1 receptor agonist, have been reported in the postmarketing
period; the data in these reports are insufficient to establish or exclude a causal
relationship between MTC and GLP-1 receptor agonist use in humans. OZEMPIC®
is contraindicated in patients with a personal or family history of MTC or in patients
with MEN 2. Counsel patients regarding the potential risk for MTC with the use of
OZEMPIC® and inform them of symptoms of thyroid tumors (e.g. a mass in the neck,
dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin
or using thyroid ultrasound is of uncertain value for early detection of MTC in patients
treated with OZEMPIC®. Such monitoring may increase the risk of unnecessary
procedures, due to the low test specificity for serum calcitonin and a high background
incidence of thyroid disease. Significantly elevated serum calcitonin value may
indicate MTC and patients with MTC usually have calcitonin values >50 ng/L. If
serum calcitonin is measured and found to be elevated, the patient should be further
evaluated. Patients with thyroid nodules noted on physical examination or neck
imaging should also be further evaluated. Pancreatitis: In glycemic control trials,
acute pancreatitis was confirmed by adjudication in 7 OZEMPIC®-treated patients (0.3
cases per 100 patient years) versus 3 in comparator-treated patients (0.2 cases per
100 patient years). One case of chronic pancreatitis was confirmed in an OZEMPIC®treated patient. In a 2-year trial, acute pancreatitis was confirmed by adjudication in 8
OZEMPIC®-treated patients (0.27 cases per 100 patient years) and 10 placebo-treated
patients (0.33 cases per 100 patient years), both on a background of standard of
care. After initiation of OZEMPIC®, observe patients carefully for signs and symptoms
of pancreatitis (including persistent severe abdominal pain, sometimes radiating to
the back and which may or may not be accompanied by vomiting). If pancreatitis
is suspected, OZEMPIC® should be discontinued and appropriate management
initiated; if confirmed, OZEMPIC® should not be restarted. Diabetic Retinopathy
Complications: In a 2-year trial involving patients with type 2 diabetes and high
cardiovascular risk, more events of diabetic retinopathy complications occurred in
patients treated with OZEMPIC® (3.0%) compared to placebo (1.8%). The absolute
risk increase for diabetic retinopathy complications was larger among patients with
a history of diabetic retinopathy at baseline (OZEMPIC® 8.2%, placebo 5.2%) than
among patients without a known history of diabetic retinopathy (OZEMPIC ® 0.7%,
placebo 0.4%). Rapid improvement in glucose control has been associated with a
temporary worsening of diabetic retinopathy. The effect of long-term glycemic control
with semaglutide on diabetic retinopathy complications has not been studied. Patients
with a history of diabetic retinopathy should be monitored for progression of diabetic
retinopathy. Never Share an OZEMPIC® Pen Between Patients: OZEMPIC®
pens must never be shared between patients, even if the needle is changed. Pensharing poses a risk for transmission of blood-borne pathogens. Hypoglycemia
with Concomitant Use of Insulin Secretagogues or Insulin: The risk of
hypoglycemia is increased when OZEMPIC® is used in combination with insulin

secretagogues (e.g., sulfonylureas) or insulin. Patients may require a lower dose of the
secretagogue or insulin to reduce the risk of hypoglycemia in this setting [see Adverse
Reactions, Drug Interactions]. Acute Kidney Injury: There have been postmarketing
reports of acute kidney injury and worsening of chronic renal failure, which may
sometimes require hemodialysis, in patients treated with GLP-1 receptor agonists.
Some of these events have been reported in patients without known underlying renal
disease. A majority of the reported events occurred in patients who had experienced
nausea, vomiting, diarrhea, or dehydration. Monitor renal function when initiating or
escalating doses of OZEMPIC® in patients reporting severe adverse gastrointestinal
reactions. Hypersensitivity: Serious hypersensitivity reactions (e.g., anaphylaxis,
angioedema) have been reported with GLP-1 receptor agonists. If hypersensitivity
reactions occur, discontinue use of OZEMPIC®; treat promptly per standard of care,
and monitor until signs and symptoms resolve. Do not use in patients with a previous
hypersensitivity to OZEMPIC® [see Contraindications]. Anaphylaxis and angioedema
have been reported with other GLP-1 receptor agonists. Use caution in a patient
with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist
because it is unknown whether such patients will be predisposed to anaphylaxis
with OZEMPIC®. Macrovascular Outcomes: There have been no clinical studies
establishing conclusive evidence of macrovascular risk reduction with OZEMPIC®.
ADVERSE REACTIONS: The following serious adverse reactions are described
below or elsewhere in the prescribing information: Risk of Thyroid C-cell Tumors [see
Warnings and Precautions]; Pancreatitis [see Warnings and Precautions]; Diabetic
Retinopathy Complications [see Warnings and Precautions]; Hypoglycemia with
Concomitant Use of Insulin Secretagogues or Insulin [see Warnings and Precautions];
Acute Kidney Injury [see Warnings and Precautions]; Hypersensitivity [see Warnings
and Precautions]. Clinical Trials Experience: Because clinical trials are conducted
under widely varying conditions, adverse reaction rates observed in the clinical trials
of a drug cannot be directly compared to rates in the clinical trials of another drug and
may not reflect the rates observed in practice. Pool of Placebo-Controlled Trials: The
data in Table 1 are derived from 2 placebo-controlled trials (1 monotherapy trial and
1 trial in combination with basal insulin) in patients with type 2 diabetes. These data
reflect exposure of 521 patients to OZEMPIC® and a mean duration of exposure to
OZEMPIC® of 32.9 weeks. Across the treatment arms, the mean age of patients was
56 years, 3.4% were 75 years or older and 55% were male. In these trials 71% were
White, 7% were Black or African American, and 19% were Asian; 21% identified as
Hispanic or Latino ethnicity. At baseline, patients had type 2 diabetes for an average
of 8.8 years and had a mean HbA1c of 8.2%. At baseline, 8.9% of the population
reported retinopathy. Baseline estimated renal function was normal (eGFR ≥90 mL/
min/1.73m2) in 57.2%, mildly impaired (eGFR 60 to 90 mL/min/1.73m2) in 35.9%
and moderately impaired (eGFR 30 to 60 mL/min/1.73m2) in 6.9% of patients. Pool
of Placebo- and Active-Controlled Trials: The occurrence of adverse reactions was
also evaluated in a larger pool of patients with type 2 diabetes participating in 7
placebo- and active-controlled glycemic control trials including two trials in Japanese
patients evaluating the use of OZEMPIC® as monotherapy and add-on therapy to oral
medications or insulin. In this pool, a total of 3150 patients with type 2 diabetes were
treated with OZEMPIC® for a mean duration of 44.9 weeks. Across the treatment arms,
the mean age of patients was 57 years, 3.2% were 75 years or older and 57% were
male. In these trials, 60% were White, 6% were Black or African American, and 31%
were Asian; 16% identified as Hispanic or Latino ethnicity. At baseline, patients had
type 2 diabetes for an average of 8.2 years and had a mean HbA1c of 8.2%. At baseline,
7.8% of the population reported retinopathy. Baseline estimated renal function was
normal (eGFR ≥90 mL/min/1.73m2) in 63.1%, mildly impaired (eGFR 60 to 90 mL/
min/1.73m2) in 34.3%, and moderately impaired (eGFR 30 to 60 mL/min/1.73m2) in
2.5% of the patients. Common Adverse Reactions: Table 1 shows common adverse
reactions, excluding hypoglycemia, associated with the use of OZEMPIC® in the pool
of placebo-controlled trials. These adverse reactions occurred more commonly on
OZEMPIC® than on placebo, and occurred in at least 5% of patients treated with
OZEMPIC®.
Table 1. Adverse Reactions in Placebo-Controlled Trials Reported in
≥5% of OZEMPIC ®-Treated Patients with Type 2 Diabetes Mellitus
Placebo
OZEMPIC® 0.5 mg OZEMPIC® 1 mg
Adverse Reaction
(N=262) %
(N=260) %
(N=261) %
Nausea
6.1
15.8
20.3
Vomiting
2.3
5.0
9.2
Diarrhea
1.9
8.5
8.8
Abdominal pain
4.6
7.3
5.7
Constipation
1.5
5.0
3.1
In the pool of placebo- and active-controlled trials and in the 2-year cardiovascular
outcomes trial, the types and frequency of common adverse reactions, excluding
hypoglycemia, were similar to those listed in Table 1. Gastrointestinal Adverse
Reactions: In the pool of placebo-controlled trials, gastrointestinal adverse reactions
occurred more frequently among patients receiving OZEMPIC® than placebo (placebo
15.3%, OZEMPIC® 0.5 mg 32.7%, OZEMPIC® 1 mg 36.4%). The majority of reports
of nausea, vomiting, and/or diarrhea occurred during dose escalation. More patients
receiving OZEMPIC® 0.5 mg (3.1%) and OZEMPIC® 1 mg (3.8%) discontinued
treatment due to gastrointestinal adverse reactions than patients receiving placebo
(0.4%). In addition to the reactions in Table 1, the following gastrointestinal adverse
reactions with a frequency of <5% were associated with OZEMPIC® (frequencies
listed, respectively, as: placebo; 0.5 mg; 1 mg): dyspepsia (1.9%, 3.5%, 2.7%),
eructation (0%, 2.7%, 1.1%), flatulence (0.8%, 0.4%, 1.5%), gastroesophageal
reflux disease (0%, 1.9%, 1.5%), and gastritis (0.8%, 0.8%, 0.4%). Other Adverse
Reactions: Hypoglycemia: Table 2 summarizes the incidence of events related to

Diabetes Pro Quarterly - Fall 2019

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