Introduction
Mounjaro (tirzepatide) is a novel once-weekly injectable medication approved by the FDA in May 2022 for the treatment of type 2 diabetes mellitus. It represents the first dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, offering a unique mechanism of action that addresses multiple pathophysiological defects in type 2 diabetes.
Mechanism of Action
Tirzepatide is a synthetic linear 39-amino acid peptide that functions as a dual agonist at both GIP and GLP-1 receptors. These receptors are incretin hormones that play crucial roles in glucose homeostasis. The drug enhances glucose-dependent insulin secretion, suppresses glucagon secretion, slows gastric emptying, and reduces food intake through central appetite regulation. The combined GIP/GLP-1 receptor agonism provides superior glycemic control and weight loss compared to selective GLP-1 receptor agonists alone.
Indications
Mounjaro is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It may be used as monotherapy or in combination with other glucose-lowering agents, including metformin, sulfonylureas, SGLT2 inhibitors, or insulin.
Dosage and Administration
Initial dose: 2.5 mg subcutaneously once weekly Maintenance dose: After 4 weeks, increase to 5 mg once weekly. Subsequent dose escalations to 7.5 mg, 10 mg, or 15 mg once weekly may be considered based on glycemic response and tolerability. Administration: Administer subcutaneously in the abdomen, thigh, or upper arm. Rotate injection sites. May be administered without regard to meals. Special Populations:- Renal impairment: No dosage adjustment necessary for mild to moderate impairment. Use caution in severe impairment.
- Hepatic impairment: No dosage adjustment recommended.
- Geriatric patients: No overall differences in safety or efficacy observed.
Pharmacokinetics
Absorption: Peak plasma concentrations achieved in 8-72 hours. Bioavailability approximately 80%. Distribution: Volume of distribution ~10.3 L. Plasma protein binding 99%. Metabolism: Proteolytic cleavage into smaller peptides and amino acids. Elimination: Half-life approximately 5 days. Primarily eliminated via catabolism with subsequent excretion in urine and feces.Contraindications
- History of serious hypersensitivity reaction to tirzepatide or any component
- Personal or family history of medullary thyroid carcinoma
- Patients with Multiple Endocrine Neoplasia syndrome type 2
Warnings and Precautions
Pancreatitis: Monitor for signs and symptoms; discontinue if pancreatitis suspected Hypoglycemia: Risk increased when used with insulin secretagogues or insulin Diabetic Retinopathy: Rapid improvement in glucose control may temporarily worsen retinopathy Acute Kidney Injury: Monitor renal function in patients reporting severe gastrointestinal reactions Hypersensitivity Reactions: Serious reactions including anaphylaxis and angioedema reported Acute Gallbladder Disease: Cholelithiasis and cholecystitis reportedDrug Interactions
Insulin Secretagogues or Insulin: Increased risk of hypoglycemia; consider dose reduction of concomitant medications Oral Medications: May delay gastric emptying and affect absorption of orally administered drugs Warfarin: Monitor INR more frequently when initiating or changing tirzepatide doseAdverse Effects
Very Common (≥10%): Nausea, diarrhea, decreased appetite, vomiting, constipation, dyspepsia, abdominal pain Common (1-10%): Injection site reactions, fatigue, hypoglycemia, gastritis, GERD, dizziness Serious: Pancreatitis, severe hypersensitivity reactions, acute kidney injury, diabetic retinopathy complications, acute gallbladder diseaseMonitoring Parameters
- HbA1c every 3 months until stable, then every 6 months
- Fasting plasma glucose
- Body weight
- Renal function (serum creatinine) at baseline and as clinically indicated
- Signs and symptoms of pancreatitis, hypersensitivity reactions, and hypoglycemia
- Diabetic retinopathy exams in patients with history of diabetic retinopathy
Patient Education
- Proper injection technique and site rotation
- Potential gastrointestinal side effects typically diminish over time
- Importance of consistent timing for weekly injections
- Recognition and management of hypoglycemia symptoms
- Need for continued adherence to diet and exercise recommendations
- Importance of informing all healthcare providers about Mounjaro use
- Storage requirements: refrigerate at 2-8°C; may be stored at room temperature up to 30°C for 21 days
References
1. FDA Prescribing Information: Mounjaro (tirzepatide). May 2022 2. Frías JP, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021;385(6):503-515 3. Min T, Bain SC. The Role of Tirzepatide, Dual GIP and GLP-1 Receptor Agonist, in the Management of Type 2 Diabetes: The SURPASS Clinical Trials. Diabetes Ther. 2021;12(1):143-157 4. Del Prato S, et al. Tirzepatide is an Effective and Safe Treatment for Type 2 Diabetes: A Phase 3 Trial. Lancet. 2021;398(10313):143-155 5. American Diabetes Association. Standards of Medical Care in Diabetes—2023. Diabetes Care. 2023;46(Suppl 1):S1-S291