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Dulaglutide (Trulicity® Injection)

Dulaglutide, marketed under the brand name Trulicity®, is a once-weekly injectable glucagon-like peptide-1 (GLP-1) receptor agonist used in the management of type 2 diabetes mellitus (T2DM). Recognized for its dual benefits in glycemic control and cardiovascular risk reduction, this article synthesizes information from the British National Formulary (BNF)Lippincott Textbook of Pharmacology, and Lange Basic & Clinical Pharmacology to provide a detailed overview of its pharmacology, clinical use, and safety profile.

Dulaglutide mimics endogenous GLP-1, a hormone that enhances glucose-dependent insulin secretion from pancreatic β-cells and suppresses glucagon release from α-cells (Lippincott Textbook of Pharmacology). Key actions include:

  • Insulin Secretion: Binds to GLP-1 receptors, activating cyclic AMP (cAMP) pathways to stimulate insulin release in response to elevated blood glucose.
  • Glucagon Suppression: Reduces postprandial glucose spikes by inhibiting glucagon secretion.
  • Gastric Emptying: Slows gastric motility, prolonging satiety and reducing appetite (Lange Basic & Clinical Pharmacology).
  • Cardiovascular Benefits: Demonstrated in the REWIND trial, dulaglutide reduces major adverse cardiovascular events (MACE) in patients with T2DM and established cardiovascular risk (BNF).
  1. Type 2 Diabetes Mellitus:
    • First-line or adjunctive therapy with lifestyle modifications and other agents (e.g., metformin, insulin).
    • Preferred for patients with cardiovascular disease due to proven risk reduction (BNF).
  2. Cardiovascular Risk Reduction:
    • Lowers incidence of non-fatal myocardial infarction, stroke, and cardiovascular death (REWIND Trial, cited in BNF).
  3. Weight Management:
    • Secondary benefit due to appetite suppression and slowed gastric emptying (Lippincott).
  • Administration: Subcutaneous injection (abdomen, thigh, or upper arm) once weekly.
  • Available Strengths: 0.75 mg, 1.5 mg, 3.0 mg, and 4.5 mg prefilled pens.
  • Titration:
    • Initial Dose: 0.75 mg weekly for glycemic control.
    • Maintenance: May escalate to 1.5 mg, 3.0 mg, or 4.5 mg weekly based on tolerance and efficacy (BNF).
  • Special Populations:
    • Renal Impairment: No dose adjustment required for mild-to-moderate impairment; use caution in severe impairment (eGFR <30 mL/min/1.73m²).
    • Hepatic Impairment: No adjustment needed (BNF).
  • Gastrointestinal: Nausea (≤20%), vomiting, diarrhea, constipation (most frequent during dose escalation).
  • Injection-site reactions: Mild erythema or itching.

Serious:

  • Pancreatitis: Monitor for severe abdominal pain; discontinue if confirmed.
  • Diabetic Retinopathy: Risk of progression in patients with pre-existing retinopathy.
  • Thyroid C-Cell Tumors: Contraindicated in personal/family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2) (BNF).
  • Acute Kidney Injury: Linked to dehydration from GI adverse effects (Lange).
  • Contraindications:
    • History of MTC or MEN2.
    • Hypersensitivity to dulaglutide or excipients.
    • Renal function, HbA1c, and signs of pancreatitis.
    • Retinopathy screening in high-risk patients.
  • Category C; avoid during pregnancy and breastfeeding due to insufficient safety data (BNF).
  • Oral Medications: Delayed absorption of drugs dependent on rapid gastric uptake (e.g., antibiotics, oral contraceptives). Administer 1 hour before dulaglutide.
  • Insulin/Sulfonylureas: Increased hypoglycemia risk; consider dose reduction.
  • Diuretics/NSAIDs: May exacerbate dehydration or renal impairment (Lippincott).
  • Generic: Dulaglutide.
  • Brand Name: Trulicity® (Eli Lilly).

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