Dulaglutide

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Pen-injector, Subcutaneous [preservative free]:

Trulicity: 0.75 mg/0.5 mL (0.5 mL); 1.5 mg/0.5 mL (0.5 mL) [contains polysorbate 80]

Pharmacology

Mechanism of Action

Dulaglutide is an agonist of human glucagon-like peptide-1 (GLP-1) receptor and augments glucose dependent insulin secretion and slows gastric emptying.

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: ~17 to 19 L

Metabolism

Degradation to amino acids by protein catabolism pathways.

Time to Peak

Plasma: 24 to 72 hours

Half-Life Elimination

~5 days

Use in Specific Populations

Special Populations: Renal Function Impairment

Renal impairment: Dulaglutide systemic exposure increased by 20%, 28%, 14%, and 12% for mild, moderate, and severe renal impairment, and ESRD, respectively.

Special Populations: Hepatic Function Impairment

Dulaglutide systemic exposure decreased by 23%, 33%, and 21% for mild, moderate, and severe hepatic impairment, respectively.

Use: Labeled Indications

Type 2 diabetes mellitus: Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (noninsulin dependent, NIDDM)

Contraindications

Serious hypersensitivity to dulaglutide or any component of the formulation; personal or family history of medullary thyroid carcinoma (MTC); patients with multiple endocrine neoplasia syndrome type 2 (MEN2)

Canadian labeling: Additional contraindications (not in US labeling): Pregnancy; breast-feeding

Dosage and Administration

Dosing: Adult

Type 2 diabetes mellitus: SubQ: Initial: 0.75 mg once weekly; may increase to 1.5 mg once weekly if inadequate glycemic response; maximum: 1.5 mg/week

Missed doses: If a dose is missed, administer as soon as possible within 3 days after the missed dose; dosing can then be resumed on the usual day of administration. If there are less than 3 days until next scheduled dose, omit the missed dose and resume administration at the next regularly scheduled weekly dose.

Dosing: Geriatric

Refer to adult dosing.

Administration

SubQ: Do not inject intravenously or intramuscularly. Inject subcutaneously into the upper arm, thigh, or abdomen; when administering within the same body region, use a different injection site each week. Administer once weekly on the same day each week, without regard to meals or time of day. The day of weekly administration may be changed, as long as the last dose was administered ≥3 days before. If using concomitantly with insulin, administer as separate injections (do not mix); may inject in the same body region as insulin, but not adjacent to one another.

Dietary Considerations

Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.

Storage

Store at 36°F to 46°F (2°C to 8°C). Do not freeze. Protect from light. If needed, each single-dose pen or prefilled syringe can be kept at room temperature, not to exceed 86°F (30°C) for a total of 14 days.

Drug Interactions

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy

Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Insulins: Glucagon-Like Peptide-1 Agonists may enhance the hypoglycemic effect of Insulins. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Consider therapy modification

Maitake: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Prothionamide: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Quinolones: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolones may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Consider therapy modification

Sulfonylureas: Glucagon-Like Peptide-1 Agonists may enhance the hypoglycemic effect of Sulfonylureas. Management: Consider sulfonylurea dose reductions when used in combination with glucagon-like peptide-1 agonists. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Adverse Reactions

>10%: Gastrointestinal: Nausea (12% to 21%), diarrhea (9% to 13%), vomiting (6% to 13%)

1% to 10%:

Cardiovascular: Sinus tachycardia (6%), prolongation P-R interval on ECG (3%), first degree atrioventricular block (2%), sustained tachycardia (2%)

Central nervous system: Fatigue (4% to 6%)

Endocrine & metabolic: Hypoglycemia (≤77%; highest incidence seen with adjunctive use of insulin glargine, prandial insulin, and sulfonylurea), severe hypoglycemia (≤3%; highest incidence seen with adjunctive use of prandial insulin)

Gastrointestinal: Abdominal pain (7% to 9%), decreased appetite (5% to 9%), dyspepsia (4% to 6%), constipation (4%), flatulence (3%), abdominal distension (2% to 3%), eructation (2%), gastroesophageal reflux disease (2%)

Immunologic: Antibody development (2%; neutralizing: <1%)

<1%, postmarketing, and/or case reports: Acute renal failure, anaphylaxis, angioedema, chronic renal failure (worsening), hypersensitivity reaction, increased serum amylase, increased serum lipase, injection site reaction, pancreatitis

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular effects: Tachycardia, PR interval prolongation, and first-degree AV block have been observed; use caution in patients with, or at risk (eg, preexisting conduction system abnormalities, underlying structural heart disease, ischemic heart disease, cardiomyopathies) for developing conduction abnormalities.
• Hypersensitivity reactions: Serious hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported; discontinue therapy in the event of a hypersensitivity reaction. Use with caution in patients with a history of angioedema or anaphylaxis to other GLP-1 receptor agonists; potential for cross-sensitivity is unknown.
• Pancreatitis: Cases of pancreatitis have been reported; monitor for signs and symptoms of pancreatitis (eg, persistent severe abdominal pain). If pancreatitis is suspected, discontinue use. Do not resume therapy if pancreatitis is confirmed. Consider antidiabetic therapies other than dulaglutide in patients with a history of pancreatitis.
• Thyroid tumors:[US Boxed Warning] Thyroid C-cell tumors have developed in animal studies with glucagon-like peptide-1 (GLP-1) receptor agonists; it is not known if dulaglutide causes thyroid C-cell tumor, including medullary thyroid carcinoma (MTC) in humans. Routine monitoring of serum calcitonin or using thyroid ultrasound monitoring is of uncertain value for early detection of MTC in patients treated with dulaglutide. Patients should be counseled on the potential risk of MTC with the use of dulaglutide and informed of symptoms of thyroid tumors (eg, neck mass, dysphagia, dyspnea, persistent hoarseness). Use is contraindicated in patients with a personal or a family history of MTC and in patients with multiple endocrine neoplasia syndrome type 2 (MEN2). Once case of MTC has been reported in a patient treated with dulaglutide and cases have also been reported in patients treated with the GLP-1 receptor agonist liraglutide; data is insufficient to establish or exclude a causal relationship. Consultation with an endocrinologist is recommended in patients with thyroid nodules on physical examination or neck imaging and in patients who develop elevated calcitonin concentrations.

Disease-related concerns:

• Bariatric surgery:

- Dehydration: Evaluate, correct, and maintain postsurgical fluid requirements and volume status prior to initiating therapy, and closely monitor the patient for the duration of therapy; acute and chronic kidney failure exacerbation may occur. A majority of cases occurred in patients with nausea, vomiting, diarrhea, and/or dehydration. Nausea is common and fluid intake may be more difficult after gastric bypass, sleeve gastrectomy, and gastric band (Mechanick 2013).

- Excessive glucagon-like peptide-1 exposure: Closely monitor for efficacy and assess for signs and symptoms of pancreatitis if therapy is initiated after surgery; gastric bypass and sleeve gastrectomy (but not gastric band) significantly increase endogenous postprandial glucagon-like peptide-1 (GLP-1) concentrations (Korner 2009; Peterli 2012). Administration of exogenous GLP-1 agonists may be redundant to surgery effects.

• Gastrointestinal disease: Use is not recommended in patients with preexisting severe gastrointestinal disease, including severe gastroparesis.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment, particularly during initiation of therapy and dose escalation. Acute renal failure and chronic renal failure exacerbation (sometimes requiring hemodialysis) have been reported; some cases have been reported in patients with no known pre-existing renal disease. A majority of reported cases occurred in patients with nausea/vomiting/diarrhea or dehydration.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Appropriate use: Diabetes mellitus: Not recommended for first-line therapy in patients inadequately controlled on diet and exercise alone. Do not use in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis; not a substitute for insulin.
• Patient education: Diabetes self-management education (DSME) is essential to maximize the effectiveness of therapy.

Monitoring Parameters

Plasma glucose, HbA_1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change [ADA 2019]), renal function (in patients reporting severe GI reactions), signs/symptoms of pancreatitis

Pregnancy

Pregnancy Considerations

Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major birth defects, stillbirth, and macrosomia (ACOG 201 2018). To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA_1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2020; Blumer 2013).

Agents other than dulaglutide are currently recommended to treat diabetes mellitus in pregnancy (ADA 2020).

Patient Education

What is this drug used for?

• It is used to lower blood sugar in patients with high blood sugar (diabetes).

Frequently reported side effects of this drug

• Lack of appetite
• Diarrhea
• Nausea
• Vomiting
• Abdominal pain
• Loss of strength and energy

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Thyroid cancer like new lump or swelling in the neck, pain in the front of the neck, persistent cough, persistent change in voice like hoarseness, or difficulty swallowing or breathing.
• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain.
• Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting.
• Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating.
• Sweating a lot
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.