Usage
- Dulaglutide is prescribed for adults and children 10 years and older with type 2 diabetes mellitus to improve glycemic control, along with diet and exercise. It is also indicated 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 and established cardiovascular disease or multiple cardiovascular risk factors.
- Pharmacological Classification: Incretin mimetic, glucagon-like peptide-1 (GLP-1) receptor agonist, antidiabetic agent.
- Mechanism of Action: Dulaglutide works by mimicking the effects of GLP-1, a natural hormone that helps regulate blood sugar levels. It stimulates insulin release when blood glucose is elevated, suppresses glucagon secretion (which raises blood glucose), slows gastric emptying, and may reduce appetite.
Alternate Names
- No alternate generic names are commonly used.
- Brand Names: Trulicity
How It Works
- Pharmacodynamics: Dulaglutide binds to and activates GLP-1 receptors, leading to increased glucose-dependent insulin secretion, decreased glucagon secretion, delayed gastric emptying, and possibly reduced appetite. These actions collectively contribute to improved glycemic control.
- Pharmacokinetics: Administered subcutaneously, dulaglutide is absorbed slowly, reaching peak concentrations in about 48 hours. It has a half-life of approximately 5 days, allowing for once-weekly administration. Dulaglutide is metabolized through proteolytic degradation, similar to endogenous peptides, with no involvement of cytochrome P450 enzymes. It is eliminated primarily through renal excretion.
- Mode of Action: Dulaglutide acts as a GLP-1 receptor agonist. GLP-1 receptors are found on pancreatic beta cells, alpha cells, and in the brain and gut. By binding to and activating these receptors, dulaglutide mimics the effects of endogenous GLP-1.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Dulaglutide’s primary mechanism involves GLP-1 receptor agonism. There is no significant interaction with CYP450 enzymes or known neurotransmitter modulation.
- Elimination Pathways: Primarily renal excretion; metabolized through proteolytic cleavage.
Dosage
Standard Dosage
Adults:
- Initial dose: 0.75 mg subcutaneously once weekly.
- Maintenance dose: May be increased to 1.5 mg once weekly if additional glycemic control is needed. Further increases to 3 mg and then to a maximum of 4.5 mg once weekly are possible at intervals of at least 4 weeks, based on clinical response.
Children (10 years and older):
- Initial dose: 0.75 mg subcutaneously once weekly.
- Maximum dose: 1.5 mg subcutaneously once weekly after at least 4 weeks at the lower dose if further glycemic control is needed.
Special Cases:
- Elderly Patients: No dosage adjustment is required based solely on age.
- Patients with Renal Impairment: No dosage adjustment is required. Use with caution in end-stage renal disease (eGFR <15 mL/min/1.73 m²), as there is limited experience in this population.
- Patients with Hepatic Dysfunction: No dosage adjustment is required. Use with caution due to limited data.
- Patients with Comorbid Conditions: Caution in patients with a history of pancreatitis or severe gastrointestinal disease, including gastroparesis. Not recommended for patients with type 1 diabetes mellitus or diabetic ketoacidosis. For patients with diabetic retinopathy, monitor closely.
Clinical Use Cases
Dulaglutide is not indicated for use in situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations such as status epilepticus or cardiac arrest. Its role is specifically in chronic glycemic management of type 2 diabetes.
Dosage Adjustments
Dose adjustments are based on the individual patient’s glycemic response and are made at intervals of at least 4 weeks as outlined above.
Side Effects
Common Side Effects
- Nausea, vomiting, diarrhea, abdominal pain, decreased appetite, constipation, dyspepsia.
Rare but Serious Side Effects
- Pancreatitis (symptoms may include persistent severe abdominal pain which may radiate to the back, with or without vomiting), gallbladder disease (including cholelithiasis), acute kidney injury, severe hypersensitivity reactions (anaphylaxis, angioedema), hypoglycemia (especially when combined with insulin or sulfonylureas), and medullary thyroid carcinoma (rare).
Long-Term Effects
- Potential long-term effects may include chronic pancreatitis, gallbladder disease, and renal impairment. Regular monitoring is essential.
Adverse Drug Reactions (ADR)
The serious side effects listed above require immediate medical attention.
Contraindications
- Hypersensitivity to dulaglutide or any of the excipients.
- Personal or family history of medullary thyroid carcinoma (MTC).
- Multiple endocrine neoplasia syndrome type 2 (MEN 2).
Drug Interactions
- Dulaglutide’s absorption may be affected by medications that slow gastric emptying.
- Concomitant use with insulin or insulin secretagogues may increase the risk of hypoglycemia. Dosage adjustment of these medications may be necessary.
- No clinically significant interactions with CYP450 enzymes are known.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Category C (data limited; animal studies show some risk). Use only if the potential benefit justifies the potential risk to the fetus.
- It is unknown whether dulaglutide is excreted in human breast milk. Caution is advised when using in breastfeeding mothers.
Drug Profile Summary
- Mechanism of Action: GLP-1 receptor agonist.
- Side Effects: Nausea, vomiting, diarrhea, abdominal pain, pancreatitis (rare), gallbladder disease (rare), hypoglycemia (when combined with other antidiabetic agents).
- Contraindications: Hypersensitivity, personal or family history of MTC, MEN 2.
- Drug Interactions: Medications affecting gastric emptying, insulin, sulfonylureas.
- Pregnancy & Breastfeeding: Caution advised. Category C.
- Dosage: Adults: 0.75-4.5 mg SC once weekly. Children (≥10 years): 0.75-1.5 mg SC once weekly.
- Monitoring Parameters: HbA1c, fasting blood glucose, postprandial blood glucose, renal function tests, signs of pancreatitis.
Popular Combinations
- Metformin: Commonly used in combination with metformin to achieve additive glycemic control.
- SGLT2 Inhibitors: May be combined with SGLT2 inhibitors to further improve glycemic control and potentially reduce cardiovascular risk.
- Insulin: Can be added to basal insulin therapy when additional glycemic control is needed.
Precautions
- Monitor renal function, especially in patients with pre-existing renal impairment.
- Monitor for signs and symptoms of pancreatitis.
- Assess and manage other comorbid conditions, such as cardiovascular disease and diabetic retinopathy.
- Educate patients about the risk of hypoglycemia, especially when combined with insulin or sulfonylureas.
- Educate patients about proper injection technique.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Dulaglutide?
A: Adults: Initial dose is 0.75 mg SC once weekly, which can be increased up to 4.5 mg once weekly based on glycemic response. Children (10 years and older): Initial dose is 0.75 mg SC once weekly, which can be increased to a maximum of 1.5 mg weekly.
Q2: How is Dulaglutide administered?
A: Subcutaneously once weekly, at any time of day, with or without food, into the abdomen, thigh, or upper arm.
Q3: What are the most common side effects?
A: Gastrointestinal side effects like nausea, vomiting, diarrhea, and abdominal pain are common.
Q4: Can Dulaglutide be used in patients with renal impairment?
A: Yes, but with caution in patients with severe renal impairment (eGFR <15 mL/min/1.73m²) or end-stage renal disease, as there is limited experience in these populations. No dose adjustment is required for milder forms of renal impairment.
Q5: What if a dose is missed?
A: If a dose is missed, it should be administered as soon as possible within 3 days (72 hours) of the missed dose. If more than 72 hours have elapsed, skip the missed dose and administer the next dose on the regularly scheduled day.
Q6: Can Dulaglutide be used during pregnancy?
A: Dulaglutide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Discuss the risks and benefits with patients of reproductive potential.
Q7: Can dulaglutide cause hypoglycemia?
A: While dulaglutide alone has a low risk of causing hypoglycemia, the risk increases when it’s used in combination with insulin or other insulin secretagogues.
Q8: How does dulaglutide affect cardiovascular risk?
A: Clinical trials have shown that dulaglutide can reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease or multiple cardiovascular risk factors.
Q9: Can dulaglutide be used in type 1 diabetes?
A: No, dulaglutide is not indicated for the treatment of type 1 diabetes or diabetic ketoacidosis. It is specifically for type 2 diabetes.
