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Tirzepatide (Mounjaro® Injection)
Tirzepatide, marketed as Mounjaro®, is a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. Approved for type 2 diabetes mellitus (T2DM), it offers superior glycemic control and weight loss compared to traditional GLP-1 agonists. This article synthesizes evidence from the British National Formulary (BNF), Lippincott Textbook of Pharmacology, and Lange Basic & Clinical Pharmacology to detail its pharmacology, clinical use, and safety profile.
Tirzepatide’s unique dual agonism targets two incretin pathways:
- GIP Receptor Activation: Enhances insulin secretion, suppresses glucagon, and promotes adipocyte energy storage.
- GLP-1 Receptor Activation: Stimulates glucose-dependent insulin release, suppresses glucagon, slows gastric emptying, and increases satiety (Lippincott).
The synergistic action improves both fasting and postprandial glucose while promoting significant weight loss (up to 15% in clinical trials) (Lange).
- Type 2 Diabetes Mellitus:
- First-line or adjunctive therapy with diet/exercise ± other agents (e.g., metformin, SGLT2 inhibitors).
- Demonstrated superior HbA1c reduction vs. GLP-1 agonists (e.g., semaglutide) in SURPASS trials (BNF).
- Weight Management:
- Off-label use supported by SURMOUNT trials, showing sustained weight loss in obesity (± diabetes).
- Cardiovascular Benefits:
Ongoing trials (e.g., SURPASS-CVOT) investigate MACE reduction
- Administration: Subcutaneous injection (abdomen, thigh, or upper arm) once weekly.
- Available Strengths: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg prefilled pens.
- Titration:
- Initial: 2.5 mg weekly for 4 weeks to minimize GI effects.
- Maintenance: Increase by 2.5 mg every 4 weeks to 5 mg, 7.5 mg, 10 mg, 12.5 mg, or 15 mg based on tolerance and efficacy (BNF).
- Special Populations:
- Renal/Hepatic Impairment: No dose adjustment for mild-to-moderate impairment. Avoid in severe impairment (limited data).
- Gastrointestinal: Nausea (≤30%), vomiting, diarrhea, constipation (dose-dependent and transient).
- Decreased appetite, dyspepsia.
Serious:
- Pancreatitis: Monitor for severe abdominal pain; discontinue if confirmed.
- Diabetic Retinopathy Complications: Risk with rapid HbA1c improvement.
- Thyroid C-Cell Tumors: Contraindicated in personal/family history of medullary thyroid carcinoma (MTC) or MEN2 (BNF).
- Gallbladder Disease: Cholelithiasis or cholecystitis reported (Lippincott).
- Contraindications:
- Personal/family history of MTC or MEN2.
Hypersensitivity to tirzepatide
- HbA1c, renal function, pancreatic enzymes, and signs of retinopathy.
- Weight and hydration status (risk of dehydration from GI effects).
Category C; avoid during pregnancy/breastfeeding (BNF).
- Oral Medications: Delayed absorption of drugs requiring rapid GI uptake (e.g., levothyroxine, antibiotics). Administer 1–4 hours before tirzepatide.
- Insulin/Sulfonylureas: Increased hypoglycemia risk; consider dose reduction.
- Warfarin: Monitor INR due to potential protein-binding interactions (Lange).
- Generic: Tirzepatide.
- Brand Name: Mounjaro® (Eli Lilly).
