Introduction
Dulaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist approved by the FDA in 2014 for the management of type 2 diabetes mellitus. Marketed under the brand name Trulicity®, this once-weekly injectable medication has demonstrated efficacy in glycemic control while offering potential cardiovascular benefits and weight reduction effects.
Mechanism of Action
Dulaglutide acts as an incretin mimetic by selectively activating GLP-1 receptors. Its mechanism includes:
- Glucose-dependent stimulation of insulin secretion from pancreatic beta cells
- Suppression of inappropriately elevated glucagon secretion from pancreatic alpha cells
- Slowing of gastric emptying
- Promotion of satiety through central nervous system effects
The molecule is engineered with an Fc portion of human IgG4, providing extended duration of action through reduced renal clearance and protection from dipeptidyl peptidase-4 (DPP-4) degradation.
Indications
- Primary indication: Improvement of glycemic control in adults with type 2 diabetes mellitus as an adjunct to diet and exercise
- Cardiovascular risk reduction: 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
Dosage and Administration
Standard dosing:- Initial dose: 0.75 mg subcutaneously once weekly
- Maintenance dose: 1.5 mg subcutaneously once weekly
- Maximum dose: 4.5 mg once weekly (after dose escalation)
- Administer any time of day, with or without meals
- Inject subcutaneously in abdomen, thigh, or upper arm
- Rotate injection sites
- Prefilled pen device with automatic needle insertion
- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: No dosage adjustment necessary
- Geriatric patients: No dosage adjustment necessary
Pharmacokinetics
Absorption: Bioavailability approximately 90% following subcutaneous administration Distribution: Volume of distribution ~19.3 L; 99% plasma protein bound Metabolism: Proteolytic degradation following binding to GLP-1 receptors Elimination: Mean half-life approximately 5 days; primarily renal elimination of degraded peptides Time to peak: 24-72 hours post-doseContraindications
- Personal or family history of medullary thyroid carcinoma
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- History of hypersensitivity to dulaglutide or any product components
- Severe gastrointestinal disease, including gastroparesis
Warnings and Precautions
Boxed Warning: Risk of thyroid C-cell tumors- Thyroid tumors found in rodent studies; human relevance unknown
- Patients should be counseled regarding potential risk symptoms
- Pancreatitis: Discontinue immediately if suspected
- Hypoglycemia: Increased risk when used with insulin secretagogues or insulin
- Renal impairment: Monitor renal function in patients reporting severe gastrointestinal reactions
- Hypersensitivity reactions: Including anaphylaxis and angioedema
- Acute gallbladder disease: Has been reported in clinical trials
Drug Interactions
Significant interactions:- Insulin secretagogues (e.g., sulfonylureas): Increased risk of hypoglycemia (consider reducing secretagogue dose)
- Oral medications: Delayed gastric emptying may affect absorption of orally administered drugs
- Warfarin: Monitor INR more frequently when initiating or changing dulaglutide dose
Adverse Effects
Common adverse reactions (>5%):- Gastrointestinal: Nausea (12-21%), diarrhea (9-13%), vomiting (6-12%), abdominal pain (6-9%)
- decreased appetite (5-9%)
- Pancreatitis
- Hypersensitivity reactions
- Severe gastrointestinal disease
- Acute kidney injury
- Gallbladder disease
Monitoring Parameters
Baseline assessment:- HbA1c level
- Renal function (serum creatinine, eGFR)
- Thyroid examination (palpation)
- Cardiovascular risk assessment
- Weight and BMI
- HbA1c every 3 months until stable, then every 6 months
- Renal function annually or as clinically indicated
- Signs and symptoms of thyroid tumors (neck mass, dysphagia, dyspnea)
- Gastrointestinal tolerance
- Hypoglycemia symptoms, especially when used with other antidiabetic agents
- Weight changes
Patient Education
Key counseling points:- Administration technique: Demonstrate proper use of prefilled pen
- Dosing schedule: Once weekly, same day each week
- Storage: Refrigerate; may be kept at room temperature for up to 14 days
- Missed dose: Administer within 3 days of missed dose; if >3 days, skip and resume regular schedule
- Report persistent severe abdominal pain (pancreatitis warning)
- Recognize hypoglycemia symptoms and management
- Report symptoms of thyroid tumors (neck mass, difficulty swallowing)
- Monitor for allergic reactions
- Continue dietary modifications and physical activity
- Regular blood glucose monitoring as directed
- Importance of comprehensive diabetes care
References
1. FDA Prescribing Information: Trulicity (dulaglutide). 2022 2. Giorgino F, et al. Lancet Diabetes Endocrinol. 2020;8(2):137-147 3. Wysham C, et al. Diabetes Care. 2021;44(3):765-773 4. Gerstein HC, et al. Lancet. 2019;394(10193):121-130 5. Dungan KM, et al. Diabetes Obes Metab. 2021;23(1):106-114 6. American Diabetes Association. Standards of Medical Care in Diabetes—2023. Diabetes Care 2023;46(Suppl 1):S1-S291
This monograph is intended for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for personalized medical recommendations.