HIGHLIGHTS OF PRESCRIBING INFORMATION
`These highlights do not include all the information needed to use
`TRULICITY safely and effectively. See full prescribing information
`for TRULICITY.
`TRULICITY (dulaglutide) injection, for subcutaneous use
`Initial U.S. Approval: 2014
`WARNING: RISK OF THYROID C-CELL TUMORS
`See full prescribing information for complete boxed warning.
`• Dulaglutide causes thyroid C-cell tumors in rats. It is unknown
`whether TRULICITY causes thyroid C-cell tumors, including
`medullary thyroid carcinoma (MTC), in humans as the human
`relevance of dulaglutide-induced rodent thyroid C-cell tumors
`has not been determined (5.1, 13.1).
`• TRULICITY is contraindicated in patients with a personal or
`family history of MTC and in patients with Multiple Endocrine
`Neoplasia syndrome type 2 (MEN 2). Counsel patients
`regarding the potential risk of MTC and symptoms of thyroid
`tumors (4, 5.1).
`
` --------------------------- RECENT MAJOR CHANGES --------------------------
`Warnings and Precautions (5.3)
`9/2021
`Warnings and Precautions (5.8)
`6/2022
` ---------------------------- INDICATIONS AND USAGE ---------------------------
`TRULICITY® is a glucagon-like peptide-1 (GLP-1) receptor agonist
`indicated:
`• as an adjunct to diet and exercise to improve glycemic control in
`adults with type 2 diabetes mellitus.
`• to reduce the risk of major adverse cardiovascular events in adults
`with type 2 diabetes mellitus who have established cardiovascular
`disease or multiple cardiovascular risk factors.
`Limitations of Use:
`• Has not been studied in patients with a history of pancreatitis.
`Consider other antidiabetic therapies in these patients (1, 5.2).
`• Not for treatment of type 1 diabetes mellitus (1).
`• Not recommended in patients with severe gastrointestinal disease,
`including severe gastroparesis (1, 5.6).
` ------------------------ DOSAGE AND ADMINISTRATION -----------------------
`• Initiate at 0.75 mg subcutaneously once weekly. Increase the dose
`to 1.5 mg once weekly for additional glycemic control.
`• If additional glycemic control is needed, increase the dose to 3 mg
`once weekly after at least 4 weeks on the 1.5 mg dose (2.1).
`• If additional glycemic control is needed, increase to the maximum
`dose of 4.5 mg once weekly after at least 4 weeks on the 3 mg
`dose. (2.1).
`• If a dose is missed, administer the missed dose as soon as possible
`if there are at least 3 days (72 hours) until the next scheduled dose
`(2.1).
`• Administer once weekly at any time of day with or without food (2.2).
`• Inject subcutaneously in the abdomen, thigh, or upper arm (2.2).
`
`
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`WARNING: RISK OF THYROID C-CELL TUMORS
`1
`INDICATIONS AND USAGE
`2 DOSAGE AND ADMINISTRATION
`2.1 Dosage
`2.2
`Important Administration Instructions
`3 DOSAGE FORMS AND STRENGTHS
`4 CONTRAINDICATIONS
`5 WARNINGS AND PRECAUTIONS
`5.1 Risk of Thyroid C-cell Tumors
`5.2 Pancreatitis
`5.3 Hypoglycemia with Concomitant Use of Insulin
`Secretagogues or Insulin
`5.4 Hypersensitivity Reactions
`5.5 Acute Kidney Injury
`
`Reference ID: 4997161
`
`
` ---------------------- DOSAGE FORMS AND STRENGTHS ---------------------
`• Injection: 0.75 mg/0.5 mL solution in a single-dose pen (3)
`• Injection: 1.5 mg/0.5 mL solution in a single-dose pen (3)
`• Injection: 3 mg/0.5 mL solution in a single-dose pen (3)
`• Injection: 4.5 mg/0.5 mL solution in a single-dose pen (3)
` ------------------------------- CONTRAINDICATIONS ------------------------------
`• Patients with a personal or family history of medullary thyroid
`carcinoma or in patients with Multiple Endocrine Neoplasia
`syndrome type 2 (4, 5.1).
`• Patients with a serious hypersensitivity reaction to TRULICITY or
`any of the product components (4, 5.4).
` ------------------------ WARNINGS AND PRECAUTIONS -----------------------
`• Thyroid C-cell Tumors: See Boxed Warning (5.1).
`• Pancreatitis: Has been reported in clinical trials. Discontinue
`promptly if pancreatitis is suspected. Do not restart if pancreatitis is
`confirmed (5.2).
`• Hypoglycemia: Concomitant use with an insulin secretagogue or
`insulin may increase the risk of hypoglycemia, including severe
`hypoglycemia. Reducing the dose of insulin secretagogue or insulin
`may be necessary (5.3).
`• Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g.,
`anaphylactic reactions and angioedema) have occurred.
`Discontinue TRULICITY and promptly seek medical advice (5.4).
`• Acute Kidney Injury: Monitor renal function in patients with renal
`impairment reporting severe adverse gastrointestinal reactions (5.5).
`• Severe Gastrointestinal Disease: Use may be associated with
`gastrointestinal adverse reactions, sometimes severe. Has not been
`studied in patients with severe gastrointestinal disease and is not
`recommended in these patients (5.6).
`• Diabetic Retinopathy Complications: Have been reported in a
`cardiovascular outcomes trial. Monitor patients with a history of
`diabetic retinopathy (5.7).
`• Acute Gallbladder Disease: If cholelithiasis or cholecystitis are
`suspected, gallbladder studies are indicated (5.8).
` ------------------------------- ADVERSE REACTIONS ------------------------------
`The most common adverse reactions, reported in ≥5% of patients
`treated with TRULICITY are: nausea, diarrhea, vomiting, abdominal
`pain, and decreased appetite (6.1).
`To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly
`and Company at 1-800-LillyRx (1-800-545-5979) or FDA at
`1-800-FDA-1088 or www.fda.gov/medwatch.
` ------------------------------- DRUG INTERACTIONS ------------------------------
`TRULICITY delays gastric emptying and has the potential to reduce
`the rate of absorption of concomitantly administered oral medications
`(7.1, 12.3).
`-----------------------USE IN SPECIFIC POPULATIONS----------------------
`• Pregnancy: TRULICITY should be used during pregnancy only if the
`potential benefit justifies the potential risk to fetus (8.1).
`See 17 for PATIENT COUNSELING INFORMATION and FDA-
`approved Medication Guide.
`
`Revised: 06/2022
`
`5.6 Severe Gastrointestinal Disease
`5.7 Diabetic Retinopathy Complications in Patients with a
`History of Diabetic Retinopathy
`5.8 Acute Gallbladder Disease
`6 ADVERSE REACTIONS
`6.1 Clinical Studies Experience
`6.2
`Immunogenicity
`6.3 Postmarketing Experience
`7 DRUG INTERACTIONS
`7.1 Oral Medications
`7.2 Concomitant Use with an Insulin Secretagogue (e.g.,
`Sulfonylurea) or with Insulin
`8 USE IN SPECIFIC POPULATIONS
`8.1 Pregnancy
`8.2 Lactation
`
`

`

`2
`
`13.2 Animal Toxicology and/or Pharmacology
`14 CLINICAL STUDIES
`14.1 Glycemic Control Trials in Adults with Type 2 Diabetes
`Mellitus
`14.2 Cardiovascular Outcomes Trial in Adults with Type 2
`Diabetes Mellitus and Cardiovascular Disease or Multiple
`Cardiovascular Risk Factors
`16 HOW SUPPLIED/STORAGE AND HANDLING
`16.1 How Supplied
`16.2 Storage and Handling
`17 PATIENT COUNSELING INFORMATION
`*Sections or subsections omitted from the full prescribing information
`are not listed.
`
`8.4 Pediatric Use
`8.5 Geriatric Use
`8.6 Renal Impairment
`8.7 Hepatic Impairment
`8.8 Gastroparesis
`10 OVERDOSAGE
`11 DESCRIPTION
`12 CLINICAL PHARMACOLOGY
`12.1 Mechanism of Action
`12.2 Pharmacodynamics
`12.3 Pharmacokinetics
`13 NONCLINICAL TOXICOLOGY
`13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility
`FULL PRESCRIBING INFORMATION
`WARNING: RISK OF THYROID C-CELL TUMORS
`• In male and female rats, dulaglutide causes a dose-related and treatment-duration-dependent increase in the
`incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure. It is unknown whether
`TRULICITY causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human
`relevance of dulaglutide-induced rodent thyroid C-cell tumors has not been determined [see Warnings and
`Precautions (5.1), and Nonclinical Toxicology (13.1)].
`• TRULICITY is contraindicated in patients with a personal or family history of MTC and in patients with Multiple
`Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC with use of
`TRULICITY and inform them of symptoms of thyroid tumors (e.g., 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 TRULICITY [see Contraindications (4) and Warnings
`and Precautions (5.1)].
`
`1
`
`INDICATIONS AND USAGE
`TRULICITY® is indicated
`• as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
`• to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction,
`or non-fatal stroke) in adults with type 2 diabetes mellitus who have established cardiovascular disease or
`multiple cardiovascular risk factors.
`Limitations of Use
`• TRULICITY has not been studied in patients with a history of pancreatitis [see Warnings and Precautions (5.2)].
`Consider other antidiabetic therapies in patients with a history of pancreatitis.
`• TRULICITY should not be used in patients with type 1 diabetes mellitus.
`• TRULICITY has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis
`and is therefore not recommended in these patients [see Warnings and Precautions (5.6)].
`DOSAGE AND ADMINISTRATION
`2
`2.1 Dosage
`• The recommended initiating dose of TRULICITY is 0.75 mg injected subcutaneously once weekly.
`• Increase the dose to 1.5 mg once weekly for additional glycemic control.
`• If additional glycemic control is needed, increase the dose to 3 mg once weekly after at least 4 weeks on the
`1.5 mg dose.
`• If additional glycemic control is needed, increase the dose to the maximum dose of 4.5 mg once weekly after at
`least 4 weeks on the 3 mg dose.
`• If a dose is missed, instruct patients to administer as soon as possible if there are at least 3 days (72 hours) until
`the next scheduled dose. If less than 3 days remain before the next scheduled dose, skip the missed dose and
`administer the next dose on the regularly scheduled day. In each case, patients can then resume their regular
`once weekly dosing schedule.
`• The day of weekly administration can be changed if necessary, as long as the last dose was administered 3 or
`more days before.
`Important Administration Instructions
`• Administer TRULICITY once weekly, any time of day, with or without food.
`
`2.2
`
`
`
`Reference ID: 4997161
`
`

`

`3
`
`3
`
`• Inject TRULICITY subcutaneously in the abdomen, thigh, or upper arm.
`• Rotate injection sites with each dose.
`• Inspect TRULICITY visually before use. It should appear clear and colorless. Do not use TRULICITY if particulate
`matter or coloration is seen.
`• When using TRULICITY with insulin, administer as separate injections and never mix. It is acceptable to inject
`TRULICITY and insulin in the same body region, but the injections should not be adjacent to each other.
`DOSAGE FORMS AND STRENGTHS
`Injection: TRULICITY is a clear and colorless solution available as:
`• 0.75 mg/0.5 mL solution in a single-dose pen
`• 1.5 mg/0.5 mL solution in a single-dose pen
`• 3 mg/0.5 mL solution in a single-dose pen
`• 4.5 mg/0.5 mL solution in a single-dose pen
`CONTRAINDICATIONS
`4
`TRULICITY is contraindicated in patients with:
`• 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 (5.1)].
`• Serious hypersensitivity reaction to dulaglutide or to any of the product components. Serious hypersensitivity
`reactions including anaphylactic reactions and angioedema have been reported with TRULICITY [see Warnings
`and Precautions (5.4)].
`5 WARNINGS AND PRECAUTIONS
`5.1 Risk of Thyroid C-cell Tumors
`In male and female rats, dulaglutide causes a dose-related and treatment-duration-dependent increase in the
`incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure [see Nonclinical Toxicology (13.1)].
`Glucagon-like peptide-1 (GLP-1) receptor agonists have induced thyroid C-cell adenomas and carcinomas in mice and
`rats at clinically relevant exposures. It is unknown whether TRULICITY will cause thyroid C-cell tumors, including
`medullary thyroid carcinoma (MTC), in humans, as the human relevance of dulaglutide-induced rodent thyroid C-cell
`tumors has not been determined.
`One case of MTC was reported in a patient treated with TRULICITY in a clinical study. This patient had pretreatment
`calcitonin levels approximately 8 times the upper limit of normal (ULN). An additional case of C-cell hyperplasia with
`elevated calcitonin levels following treatment was reported in the cardiovascular outcomes trial (REWIND). 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.
`TRULICITY 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 TRULICITY 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 TRULICITY. 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
`values 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.
`5.2 Pancreatitis
`In a pooled analysis from the original registration studies, 12 (3.4 cases per 1000 patient years) pancreatitis-related
`adverse reactions were reported in patients exposed to TRULICITY versus 3 in non-incretin comparators (2.7 cases per
`1000 patient years). An analysis of adjudicated events revealed 5 cases of confirmed pancreatitis in patients exposed to
`TRULICITY (1.4 cases per 1000 patient years) versus 1 case in non-incretin comparators (0.88 cases per 1000 patient
`years).
`Based on an analysis of adjudicated events in a clinical study evaluating Trulicity 1.5 mg, 3 mg, or 4.5 mg once
`weekly, pancreatitis occurred in 1 patient exposed to TRULICITY 1.5 mg (0.2%), in 2 patients exposed to TRULICITY
`3 mg (0.3%), and 3 patients exposed to TRULICITY 4.5 mg (0.5%).
`After initiation of TRULICITY, observe patients carefully for signs and symptoms of pancreatitis, including persistent
`severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting. If
`pancreatitis is suspected, promptly discontinue TRULICITY. If pancreatitis is confirmed, TRULICITY should not be
`
`
`Reference ID: 4997161
`
`

`

`restarted. TRULICITY has not been evaluated in patients with a prior history of pancreatitis. Consider other antidiabetic
`therapies in patients with a history of pancreatitis.
`5.3 Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin
`Patients receiving TRULICITY in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have
`an increased risk of hypoglycemia, including severe hypoglycemia [see Adverse Reactions (6.1) and Drug Interactions
`(7)].
`
`4
`
`The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly
`administered insulin secretagogue) or insulin. Inform patients using these concomitant medications of the risk of
`hypoglycemia and educate them on the signs and symptoms of hypoglycemia.
`5.4 Hypersensitivity Reactions
`There have been postmarketing reports of serious hypersensitivity reactions including anaphylactic reactions and
`angioedema in patients treated with TRULICITY [see Adverse Reactions (6.3)]. If a hypersensitivity reaction occurs,
`discontinue TRULICITY; treat promptly per standard of care, and monitor until signs and symptoms resolve. Do not use in
`patients with a previous hypersensitivity reaction to TRULICITY [see Contraindications (4)].
`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 TRULICITY.
`5.5 Acute Kidney Injury
`In patients treated with GLP-1 receptor agonists, including TRULICITY, there have been postmarketing reports of
`acute renal failure and worsening of chronic renal failure, which may sometimes require hemodialysis. Some of these
`events were reported in patients without known underlying renal disease. A majority of reported events occurred in
`patients who had experienced nausea, vomiting, diarrhea, or dehydration. Because these reactions may worsen renal
`function, use caution when initiating or escalating doses of TRULICITY in patients with renal impairment. Monitor renal
`function in patients with renal impairment reporting severe adverse gastrointestinal reactions [see Use in Specific
`Populations (8.6)].
`5.6 Severe Gastrointestinal Disease
`Use of TRULICITY may be associated with gastrointestinal adverse reactions, sometimes severe [see Adverse
`Reactions (6.1)]. TRULICITY has not been studied in patients with severe gastrointestinal disease, including severe
`gastroparesis, and is therefore not recommended in these patients.
`5.7 Diabetic Retinopathy Complications in Patients with a History of Diabetic Retinopathy
`In a cardiovascular outcomes trial with a median follow up of 5.4 years involving patients with type 2 diabetes with
`established cardiovascular disease or multiple cardiovascular risk factors, diabetic retinopathy complications occurred in
`patients treated with TRULICITY 1.5 mg (1.9%) and placebo (1.5%). These events were prospectively ascertained as a
`secondary composite endpoint. The proportion of patients with diabetic retinopathy complications was larger among
`patients with a history of diabetic retinopathy at baseline (TRULICITY 8.5%, placebo 6.2%) than among patients without a
`known history of diabetic retinopathy (TRULICITY 1%, placebo 1%).
`Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy.
`Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy.
`5.8 Acute Gallbladder Disease
`Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor
`agonist trials and postmarketing. In a cardiovascular outcomes trial with a median follow up of 5.4 years, cholelithiasis
`occurred at a rate of 0.62/100 patient-years in TRULICITY-treated patients and 0.56/100 patient-years in placebo-treated
`patients after adjusting for prior cholecystectomy. Serious events of acute cholecystitis were reported in 0.5% and 0.3% of
`patients on TRULICITY and placebo respectively. If cholelithiasis is suspected, gallbladder studies and appropriate clinical
`follow-up are indicated.
`6
`ADVERSE REACTIONS
`The following serious reactions are described below or elsewhere in the prescribing information:
`• Risk of Thyroid C-cell Tumors [see Warnings and Precautions (5.1)]
`• Pancreatitis [see Warnings and Precautions (5.2)]
`• Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin [see Warnings and Precautions (5.3)]
`• Hypersensitivity Reactions [see Warnings and Precautions (5.4)]
`• Acute Kidney Injury [see Warnings and Precautions (5.5)]
`• Severe Gastrointestinal Disease [see Warnings and Precautions (5.6)]
`
`
`
`Reference ID: 4997161
`
`

`

`5
`
`• Diabetic Retinopathy Complications in Patients with a History of Diabetic Retinopathy [see Warnings and
`Precautions (5.7)]
`• Acute Gallbladder Disease [see Warnings and Precautions (5.8)]
`6.1 Clinical Studies Experience
`Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the
`clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect
`the rates observed in practice.
`Pool of Placebo-controlled Trials for TRULICITY 0.75 mg and 1.5 mg Doses
`The data in Table 1 are derived from a pool of placebo-controlled trials and include 1670 patients exposed to
`TRULICITY with a mean duration of exposure of 23.8 weeks [see Clinical Studies (14)]. The mean age of patients was 56
`years, 1% were 75 years or older and 53% were male. The population was 69% White, 7% Black or African American,
`13% Asian; 30% were of Hispanic or Latino ethnicity. At baseline, the population had diabetes for an average of 8 years, a
`mean HbA1c of 8.0%, and 2.5% of the population reported retinopathy. Baseline estimated renal function was normal or
`mildly impaired (eGFR ≥60 mL/min/1.73 m2) in 96%.
`Table 1 shows adverse reactions, excluding hypoglycemia, occurring in ≥5% of TRULICITY treated patients and
`more commonly than placebo in a pool of placebo-controlled trials.
`
`Table 1: Adverse Reactions in Pool of Placebo-Controlled Trials Occurring in ≥5% of TRULICITY-Treated Patients
`Adverse Reaction
`Placebo
`TRULICITY 0.75 mg
`TRULICITY 1.5 mg
`(N=568)
`(N=836)
`(N=834)
`%
`%
`%
`5.3
`12.4
`21.1
`Nausea
`6.7
`8.9
`12.6
`Diarrheaa
`2.3
`6.0
`12.7
`Vomitingb
`4.9
`6.5
`9.4
`Abdominal Painc
`1.6
`4.9
`8.6
`Decreased Appetite
`2.3
`4.1
`5.8
`Dyspepsia
`2.6
`4.2
`5.6
`Fatigued
`a Includes diarrhea, fecal volume increased, frequent bowel movements.
`Includes retching, vomiting, vomiting projectile.
`b
`Includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, abdominal tenderness, gastrointestinal pain.
`Includes fatigue, asthenia, malaise.
`d
` Note: Percentages reflect the number of patients that reported at least 1 treatment-emergent occurrence of the adverse reaction.
`
`Gastrointestinal Adverse Reactions
`In the pool of placebo-controlled trials, gastrointestinal adverse reactions occurred more frequently among patients
`receiving TRULICITY than placebo (placebo 21.3%, 0.75 mg 31.6%, 1.5 mg 41.0%). More patients receiving TRULICITY
`0.75 mg (1.3%) and TRULICITY 1.5 mg (3.5%) discontinued treatment due to gastrointestinal adverse reactions than
`patients receiving placebo (0.2%). Investigators graded the severity of gastrointestinal adverse reactions occurring on
`0.75 mg and 1.5 mg of TRULICITY as “mild” in 58% and 48% of cases, respectively, “moderate” in 35% and 42% of
`cases, respectively, or “severe” in 7% and 11% of cases, respectively.
`The following adverse reactions were reported more frequently in TRULICITY-treated patients than placebo
`(frequencies listed, respectively, as: placebo; 0.75 mg; 1.5 mg): constipation (0.7%, 3.9%, 3.7%), flatulence (1.4%, 1.4%,
`3.4%), abdominal distension (0.7%, 2.9%, 2.3%), gastroesophageal reflux disease (0.5%, 1.7%, 2.0%), and eructation
`(0.2%, 0.6%, 1.6%).
`TRULICITY 3 mg and 4.5 mg Doses
`Table 2 shows adverse reactions occurring ≥5% in any of the treatment groups through 36 weeks in a clinical trial
`with 1842 patients treated with Trulicity 1.5 mg, 3 mg, or 4.5 mg once weekly as an add-on to metformin. The adverse
`reaction profile is consistent with previous clinical trials.
`
`
`c
`
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`Reference ID: 4997161
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`

`

`6
`
`Adverse Reaction
`
`Table 2: Adverse Reactions Occurring in ≥5% of Patients Receiving TRULICITY 1.5 mg, 3 mg, or 4.5 mg in a
`Clinical Trial through 36 Weeksa
`TRULICITY 1.5 mg
`TRULICITY 3 mg
`(N=612)
`(N=616)
`%
`%
`13.4
`15.6
`Nausea
`7.0
`11.4
`Diarrhea
`5.6
`8.3
`Vomiting
`2.8
`5.0
`Dyspepsia
`a Percentages reflect the number of patients that reported at least 1 treatment-emergent occurrence of the adverse reaction.
`
`Other Adverse Reactions
`Hypoglycemia
`Table 3 summarizes the incidence of hypoglycemia in the placebo-controlled clinical studies: episodes with a
`glucose level <54 mg/dL with or without symptoms, and severe hypoglycemia, defined as an episode requiring the
`assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.
`
`
`TRULICITY 4.5 mg
`(N=614)
`%
`16.4
`10.7
`9.3
`2.6
`
`Table 3: Incidence (%) of Hypoglycemia in Placebo-Controlled Trials
`
`Placebo
`
`TRULICITY 0.75 mg
`
`TRULICITY 1.5 mg
`
`N=302
`0.3
`0
`
`N=280
`2.1
`0
`
`-
`
`-
`
`-
`
`-
`-
`-
`
`N=141
`0.7
`0.7
`
`N=304
`0.7
`0
`
`N=279
`0
`0
`
`N=239
`3.3
`
`0
`
`N=150
`14.7
`0.7
`
`N=142
`0.7
`0
`
`
`Add-on to Metformin
`(26 weeks)
`Hypoglycemia with a
`glucose level <54 mg/dL
`Severe hypoglycemia
`Add-on to Metformin + Pioglitazone
`(26 weeks)
`Hypoglycemia with a
`glucose level <54 mg/dL
`Severe hypoglycemia
`Add-on to Glimepiride
`(24 weeks)
`Hypoglycemia with a
`glucose level <54 mg/dL
`0
`Severe hypoglycemia
`In Combination with Insulin Glargine ± Metformin
`N=150
`(28 weeks)
`Hypoglycemia with a
`9.3
`glucose level <54 mg/dL
`Severe hypoglycemia
`0
`Add-on to SGLT2i ± Metformin
`(24 weeks)
`Hypoglycemia with a
`glucose level <54 mg/dL
`Severe hypoglycemia
`
`Hypoglycemia was more frequent when TRULICITY was used in combination with a sulfonylurea or insulin than
`when used with non-secretagogues. In a 78-week clinical trial, hypoglycemia (glucose level <54 mg/dL) occurred in 20%
`and 21% of patients when TRULICITY 0.75 mg and 1.5 mg, respectively, were co-administered with a sulfonylurea.
`
`N=177
`0
`0
`
`N=141
`1.4
`0
`
`N=60
`0
`
`N=140
`0.7
`0
`
`
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`Reference ID: 4997161
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`

`

`7
`
`Severe hypoglycemia occurred in 0% and 0.7% of patients when TRULICITY 0.75 mg and 1.5 mg, respectively, were co-
`administered with a sulfonylurea. In a 52-week clinical trial, hypoglycemia (glucose level <54 mg/dL) occurred in 77% and
`69% of patients when TRULICITY 0.75 mg and 1.5 mg, respectively, were co-administered with prandial insulin. Severe
`hypoglycemia occurred in 2.7% and 3.4% of patients when TRULICITY 0.75 mg and 1.5 mg, respectively, were co-
`administered with prandial insulin. Refer to Table 3 for the incidence of hypoglycemia in patients treated in combination
`with basal insulin glargine.
`In the clinical trial with patients on TRULICITY 1.5 mg, TRULICITY 3 mg, or TRULICITY 4.5 mg once weekly, as
`add-on to metformin, incidences of hypoglycemia (glucose level <54 mg/dL) through 36 weeks were 1.1%, 0.3%, and
`1.1%, respectively, and incidences of severe hypoglycemia were 0.2%, 0%, and 0.2%, respectively.
`Cholelithiasis and Cholecystitis
`In a cardiovascular outcomes trial with a median follow up of 5.4 years, cholelithiasis occurred at a rate of 0.62/100
`patient-years in TRULICITY-treated patients and 0.56/100 patient-years in placebo-treated patients after adjusting for
`prior cholecystectomy. Serious events of acute cholecystitis were reported in 0.5% and 0.3% of patients on TRULICITY
`and placebo respectively.
`Heart Rate Increase and Tachycardia-Related Adverse Reactions
`TRULICITY 0.75 mg and 1.5 mg resulted in a mean increase in heart rate (HR) of 2-4 beats per minute (bpm).
`Adverse reactions of sinus tachycardia were reported more frequently in patients exposed to TRULICITY. Sinus
`tachycardia was reported in 3.0%, 2.8%, and 5.6% of patients treated with placebo, TRULICITY 0.75 mg and TRULICITY
`1.5 mg, respectively. Persistence of sinus tachycardia (reported at more than 2 visits) was reported in 0.2%, 0.4% and
`1.6% of patients treated with placebo, TRULICITY 0.75 mg and TRULICITY 1.5 mg, respectively. Episodes of sinus
`tachycardia, associated with a concomitant increase from baseline in heart rate of ≥15 beats per minute, were reported in
`0.7%, 1.3% and 2.2% of patients treated with placebo, TRULICITY 0.75 mg and TRULICITY 1.5 mg, respectively.
`Hypersensitivity
`Systemic hypersensitivity adverse reactions, sometimes severe (e.g., severe urticaria, systemic rash, facial edema,
`lip swelling), occurred in 0.5% of patients on TRULICITY in clinical studies.
`Injection-site Reactions
`In the placebo-controlled studies, injection-site reactions (e.g., injection-site rash, erythema) were reported in 0.5%
`of TRULICITY-treated patients and in 0.0% of placebo-treated patients.
`PR Interval Prolongation and Adverse Reactions of First-Degree Atrioventricular (AV) Block
`A mean increase from baseline in PR interval of 2-3 milliseconds was observed in TRULICITY-treated patients in
`contrast to a mean decrease of 0.9 milliseconds in placebo-treated patients. The adverse reaction of first-degree AV block
`occurred more frequently in patients treated with TRULICITY than placebo (0.9%, 1.7% and 2.3% for placebo,
`TRULICITY 0.75 mg and TRULICITY 1.5 mg, respectively). On electrocardiograms, a PR interval increase to at least 220
`milliseconds was observed in 0.7%, 2.5% and 3.2% of patients treated with placebo, TRULICITY 0.75 mg and TRULICITY
`1.5 mg, respectively.
`Amylase and Lipase Increase
`Patients exposed to TRULICITY had mean increases from baseline in lipase and/or pancreatic amylase of 14% to
`20%, while placebo-treated patients had mean increases of up to 3%.
`6.2
`Immunogenicity
`In clinical studies, 64 (1.6%) TRULICITY-treated patients developed anti-drug antibodies (ADAs) to the active
`ingredient in TRULICITY (i.e., dulaglutide).
`Of the 64 dulaglutide-treated patients that developed dulaglutide ADAs, 34 patients (0.9% of the overall population)
`had dulaglutide-neutralizing antibodies, and 36 patients (0.9% of the overall population) developed antibodies against
`native GLP-1.
`The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally,
`the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several
`factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and
`underlying disease. For these reasons, the incidence of antibodies to dulaglutide cannot be directly compared with the
`incidence of antibodies of other products.
`6.3 Postmarketing Experience
`The following additional adverse reactions have been reported during post-approval use of TRULICITY. Because
`these events are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate
`their frequency or establish a causal relationship to drug exposure.
`• Anaphylactic reactions, angioedema.
`• Acute renal failure or worsening of chronic renal failure, sometimes requiring hemodialysis.
`
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`Reference ID: 4997161
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`8
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`• Hepatobiliary: cholecystitis, cholelithiasis requiring cholecystectomy, cholestasis, elevation of liver enzymes,
`hepatitis.
`DRUG INTERACTIONS
`7
`7.1 Oral Medications
`TRULICITY delays gastric emptying and thus has the potential to reduce the rate of absorption of concomitantly
`administered oral medications. The delay in gastric emptying is dose-dependent but is attenuated with the recommended
`dose escalation to higher doses of TRULICITY [see Dosage and Administration (2.1)]. The delay is largest after the first
`dose and diminishes with subsequent doses. In clinical pharmacology studies, TRULICITY 1.5 mg did not affect the
`absorption of the tested orally administered medications to a clinically relevant degree [see Clinical Pharmacology (12.3)].
`There is limited experience with the use of concomitant medications in clinical trials with TRULICITY doses of 3 mg and
`4.5 mg.
`Monitor drug levels of oral medications with a narrow therapeutic index (e.g., warfarin) when concomitantly
`administered with TRULICITY.
`7.2 Concomitant Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin
`When initiating TRULICITY, consider reducing the dose of concomitantly administered insulin secretagogues (such
`as sulfonylureas) or insulin to reduce the risk of hypoglycemia [see Warnings and Precautions (5.3) and Adverse
`Reactions (6.1)].
`8
`USE IN SPECIFIC POPULATIONS
`8.1 Pregnancy
`Risk Summary
`Limited data with TRULICITY in pregnant women are not sufficient to determine a drug-associated risk for major
`birth defects and miscarriage. There are clinical considerations regarding the risks of poorly controlled diabetes in
`pregnancy [see Clinical Considerations]. Based on animal reproduction studies, there may be risks to the fetus from
`exposure to dulaglutide during pregnancy. TRU