Generic Name

Dulaglutide

Brand Names

*Trulicity*) for adjunctive weight loss in patients with overweight/obesity and at least one weight‑related comorbidity.

Mechanism

Dulaglutide is a *long‑acting glucagon‑like peptide‑1 (GLP‑1) receptor agonist*.
• Mimics endogenous GLP‑1, binding to the GLP‑1 receptor on pancreatic β‑cells.
• Enhances glucose‑dependent insulin secretion while inhibiting glucagon release, lowering post‑prandial glucose.
• Slows gastric emptying, contributing to post‑prandial glucose control and satiety.
• Acts centrally to reduce appetite, yielding weight loss in many patients.

Pharmacokinetics

• Formulation: 100 µg recombinant human GLP‑1 fused to an Fc fragment of IgG1, stabilizing the peptide.
• Absorption: Subcutaneous injection; peak plasma concentration in ~2–12 h, depending on dose.
• Distribution: High plasma protein binding (~99 %).
• Metabolism: Proteolytic cleavage by dipeptidyl peptidase‑4 (DPP‑4) and other peptidases; also by endocytosis into cells.
• Elimination: Renally filtered and partially excreted via glomerular filtration; half‑life ≈12–14 days, allowing once‑weekly dosing.
• Special populations: No dose adjustment in mild–moderate renal or hepatic impairment; caution in end‑stage renal disease (ESRD) until further data.

Indications

• Type 2 Diabetes Mellitus (T2DM): Adjunct to diet and exercise for glycaemic control.
• Weight Management: FDA‑approved (under the brand name *Trulicity*) for adjunctive weight loss in patients with overweight/obesity and at least one weight‑related comorbidity.
• Combination Therapy: Often combined with metformin, basal insulin, or other glucose‑lowering agents.

Contraindications

• Contraindicated:
• Personal or family history of medullary thyroid carcinoma (MTC).
• Multiple endocrine neoplasia syndrome type 2 (MEN 2).
• Warnings:
• Pancreatitis: Reported cases; discontinue if persistent abdominal pain or elevated lipase.
• Hypoglycaemia: Rare alone, increased risk when combined with sulfonylureas or insulin.
• Renal impairment: Monitor; no dose adjustment needed, but use with caution in ESRD.
• Thyroid C‑cell hyperplasia: Long‑term rodent studies show increased incidence; human data limited.

Dosing

• Initial dose: 0.75 mg once weekly, subcutaneously.
• Maintenance dose: Increase to 1.5 mg weekly after 4 weeks if glycaemic target not achieved.
• Maximum dose: 3.0 mg/week (two 1.5‑mg pens).
• Injection sites: Thigh, abdomen, or upper arm; rotate sites daily.
• Treatment duration: Indefinite; assess efficacy every 3–6 months.

Adverse Effects

Common (≥10 %)
• Nausea, vomiting, diarrhea
• Reduced appetite
• Injection‑site reactions (pain, erythema, pruritus)

Serious (≤1 %)
• Acute pancreatitis
• Hypoglycaemia (with concomitant agents)
• Thyroid C‑cell tumors (in animal models; risk not confirmed in humans)

Adverse effect management
• Gradual dose titration
• Fluid intake for GI symptoms
• Monitor blood glucose; adjust concomitant agents if hypoglycaemia occurs.

Monitoring

• HbA1c: Baseline, 3 months, then every 6 months.
• Body weight: Baseline and at each visit.
• Renal function: eGFR at baseline and annually.
• Liver enzymes: ALT/AST at baseline, then every 6–12 months.
• Serums lipase: If abdominal pain or risk factors.
• Thyroid panel: Not routinely required unless clinical suspicion.

Clinical Pearls

• Once‑weekly convenience: The long‐acting Fc fusion allows a single injection that achieves week‑long glucose regulation, improving adherence in busy clinical settings.
• Weight‑loss synergy: When paired with a low‑calorie diet, dulaglutide can produce an average weight loss of 5‑7 % over 6 months—useful in T2DM patients with obesity.
• Glucose‑dependent action: Lower risk of hypoglycaemia versus sulfonylureas; essential for patients using insulin or sulfonylureas.
• Kidney‑safer profile: Unlike basal insulin, no dose adjustment in moderate CKD; beneficial for patients with T2DM and renal compromise.
• Pituitary‑release: A small rise in growth hormone and insulin‑like growth factor‑1 (IGF‑1) is observed; generally benign but monitor in patients with pituitary tumors or Laron syndrome.
• Travel & dermal elimination: Injection site reactions may be reduced by applying a gentle pressure hold for 30 seconds; avoid scarred or cutaneous infection sites.

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• *Authoritative source: FDA prescribing information, ADA Standards of Care 2025, and peer‑reviewed pharmacology texts. For patient‑specific guidance, always refer to the most recent product monograph.*