Indications

Adjunct to diet and exercise for improving glycemic control in adults with type 2 diabetes mellitus.
Limitations of use:
- Not studied in patients with a history of pancreatitis.
- Not indicated for type 1 diabetes mellitus.

Pharmacology Tirzepatide is a dual GIP receptor and GLP-1 receptor agonist. It is a 39-amino-acid modified peptide with a C20 fatty diacid moiety that binds albumin, prolonging half-life. It enhances insulin secretion (first and second phase) and reduces glucagon levels in a glucose-dependent manner.

Dosage & Administration

Route: Subcutaneous injection.
Starting dose: 2.5 mg once weekly (initiation only, not for glycemic control).
Titration: Increase to 5 mg after 4 weeks; further increments of 2.5 mg every ≥4 weeks if needed.
Maximum dose: 15 mg once weekly.
Missed dose: Administer within 4 days; if >4 days, skip and continue regular schedule.
Administration: Inject in abdomen, thigh, or upper arm. Rotate sites. Do not mix with insulin, though both may be injected in the same region separately.
Handling: Do not freeze. Protect from light. Inspect syringes for particulate matter/discoloration.

Interactions

Reduce dose of insulin or sulfonylureas to lower hypoglycemia risk.
Delays gastric emptying → may affect absorption of oral drugs (e.g., warfarin).
Oral contraceptives: switch to non-oral or add barrier method for 4 weeks after initiation or dose escalation.

Contraindications

Hypersensitivity to tirzepatide or components.
Personal/family history of medullary thyroid carcinoma (MTC).
Patients with MEN 2.

Side Effects

Common: Nausea, diarrhea, decreased appetite, vomiting, constipation, dyspepsia, abdominal pain.

Pregnancy & Lactation

Use only if benefits outweigh risks. Poorly controlled diabetes poses risks to mother and fetus.
Breastfeeding: weigh maternal need against potential infant exposure.

Precautions & Warnings

Counsel on thyroid tumor risk (MTC).
Monitor for pancreatitis; discontinue if suspected.
Adjust concomitant insulin/secretagogues to reduce hypoglycemia risk.
Monitor renal function in impaired patients.
Monitor progression of diabetic retinopathy.
Evaluate gallbladder if cholelithiasis suspected.

Special Populations

Not established in patients <18 years.