Trulicity

• Type 2 Diabetes Mellitus:
• As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
• Can be used as monotherapy when metformin is inappropriate due to intolerance or contraindications.
• Used in combination with other antidiabetic agents including insulin.
• Cardiovascular Risk Reduction:
• To reduce the risk of major adverse cardiovascular events (MACE) such as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke in adults with type 2 diabetes and established cardiovascular disease.

• Adults:
• Initial dose: 0.75 mg subcutaneously once weekly.
• Dose may be increased to 1.5 mg once weekly based on glycemic response after at least 4 weeks.
• Maximum dose: 4.5 mg once weekly.
• Administration Route:
• Subcutaneous injection in the abdomen, thigh, or upper arm.
• Administer without regard to meals.
• Special Populations:
• Elderly: No initial dose adjustment required; use caution due to risk of hypoglycemia.
• Renal Impairment: Use with caution in severe renal impairment; no dose adjustment recommended but monitor closely.
• Hepatic Impairment: No dose adjustment required.
• Pediatrics:
• Safety and efficacy not established in patients under 18 years.

Dulaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist. It binds to GLP-1 receptors on pancreatic beta cells, stimulating glucose-dependent insulin secretion. It also suppresses glucagon secretion from alpha cells in a glucose-dependent manner, reduces hepatic glucose production, and slows gastric emptying. These combined effects lower blood glucose levels postprandially and fasting. Additionally, dulaglutide promotes satiety, which may contribute to weight loss. The extended half-life allows once-weekly dosing.

• Absorption:
  Slowly absorbed after subcutaneous injection; peak plasma concentration occurs approximately 48 hours post-dose.
• Bioavailability:
  Approximately 47%.
• Distribution:
  Volume of distribution ~6.3 L; plasma protein binding not significant.
• Metabolism:
  Degraded via proteolytic pathways into small peptides and amino acids; not metabolized by CYP enzymes.
• Half-life:
  Approximately 4.7 days, supporting once-weekly administration.
• Excretion:
  Excreted primarily via catabolic pathways; no significant renal or hepatic excretion of intact drug.

• Pregnancy:
  No adequate well-controlled studies in pregnant women; use only if potential benefit justifies risk. Animal studies have not demonstrated direct harm.
• Lactation:
  Unknown if excreted in human milk. Caution advised when administered to breastfeeding women.

• Primary Therapeutic Class: Antidiabetic agent
• Subclass: GLP-1 receptor agonist (incretin mimetic)

• Known hypersensitivity to dulaglutide or any component of the formulation.
• Personal or family history of medullary thyroid carcinoma (MTC).
• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
• Use in patients with severe gastrointestinal disease (e.g., gastroparesis).

• Thyroid C-cell Tumors:
  Risk of thyroid C-cell tumors observed in rodents; unknown in humans. Monitor for thyroid nodules or symptoms.
• Pancreatitis:
  Use with caution; discontinue if pancreatitis suspected.
• Hypoglycemia:
  Risk increased when combined with insulin or sulfonylureas; dose adjustments may be necessary.
• Gastrointestinal Effects:
  Nausea, vomiting, diarrhea are common; monitor volume status in patients at risk of dehydration.
• Renal Impairment:
  Monitor closely in patients with renal impairment, especially if experiencing gastrointestinal side effects.

Common:

• Nausea
• Diarrhea
• Vomiting
• Abdominal pain
• Decreased appetite
• Indigestion

Serious/Rare:

• Pancreatitis
• Hypersensitivity reactions (rash, angioedema, anaphylaxis)
• Thyroid tumors (rare)
• Hypoglycemia (primarily with concomitant insulin or sulfonylureas)

• Insulin and Sulfonylureas:
  Increased risk of hypoglycemia; dose adjustments recommended.
• Oral Medications:
  Slowed gastric emptying may alter absorption; monitor clinical response for drugs with narrow therapeutic index.
• No significant CYP450 interactions due to peptide nature and proteolytic metabolism.

• Recognized in ADA and EASD guidelines as a preferred injectable therapy for type 2 diabetes patients with established cardiovascular disease.
• Newer studies support cardiovascular risk reduction benefits beyond glycemic control.
• Recent label updates emphasize monitoring for pancreatitis and thyroid neoplasms.

• Store refrigerated at 2°C to 8°C (36°F to 46°F).
• Do not freeze.
• Protect from light.
• If needed, can be kept at room temperature up to 30°C (86°F) for a maximum of 14 days.
• Discard if exposed to temperatures outside recommended range.