Indications

Tirzep is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of use:

It has not been studied in patients with a history of pancreatitis.
It is not indicated for use in patients with type 1 diabetes mellitus.

Pharmacology

Tirzepatide is a dual GIP and GLP‑1 receptor agonist. It is a 39‑amino‑acid modified peptide with a C20 fatty‑acid moiety that enables albumin binding and prolongs its half‑life. It selectively binds to and activates both GIP and GLP‑1 receptors — the targets for native GIP and GLP‑1. It enhances first‑ and second‑phase insulin secretion and reduces glucagon levels in a glucose‑dependent manner.

Dosage & Administration

Route: Subcutaneous injection. Dosing instructions:

Recommended starting dose: 2.5 mg once weekly (for treatment initiation, not for glycemic control).
After 4 weeks, increase to 5 mg once weekly.
If additional glycemic control is needed, increase by 2.5 mg increments after at least 4 weeks on the current dose.
Maximum dose: 15 mg once weekly.
If a dose is missed, administer as soon as possible within 4 days (96 hours); if more than 4 days have passed, skip the missed dose and resume the regular schedule.
The day of weekly administration may be changed if at least 3 days (72 hours) separate doses.

Preparation and administration:

The needle cover of the pre‑filled syringe contains dry natural rubber (latex derivative) that may cause allergic reactions.
Do not freeze. Protect from light.
Inspect visually for particulate matter or discoloration; do not use if present.
Handle carefully; do not use if dropped.
Do not dilute or mix with other drug solutions.
Administer once weekly, any time of day, with or without food.
Inject subcutaneously in the abdomen, thigh, or upper arm; rotate sites.
When used with insulin, inject separately and never mix. Injections may be in the same body region but not adjacent.

Interactions

Consider reducing the dose of insulin secretagogues (e.g., sulfonylureas) or insulin to lower hypoglycemia risk.
Tirzepatide delays gastric emptying and may affect absorption of oral medications.
Monitor patients on drugs with narrow therapeutic indices (e.g., warfarin).
Advise patients using oral hormonal contraceptives to switch to non‑oral or add barrier methods for 4 weeks after initiation and after each dose escalation. Non‑oral contraceptives are not affected.

Contraindications

Known hypersensitivity to tirzepatide or any component.
Personal or family history of medullary thyroid carcinoma (MTC).
Patients with multiple endocrine neoplasia syndrome type 2 (MEN 2).

Side Effects

Common side effects include nausea, diarrhea, decreased appetite, vomiting, constipation, dyspepsia, and abdominal pain.

Pregnancy & Lactation

Poorly controlled diabetes during pregnancy poses risks to mother and fetus. Tirzepatide should be used only if potential benefits justify potential risks. Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need and possible adverse effects on the infant.

Precautions & Warnings

Counsel patients about the risk of MTC and symptoms of thyroid tumors.
Observe for signs of pancreatitis; discontinue if suspected.
Reduce insulin or secretagogue doses to lower hypoglycemia risk.
Discontinue if hypersensitivity reactions occur.
Monitor renal function when initiating or increasing doses in patients with renal impairment.
Monitor for progression of diabetic retinopathy.
If cholelithiasis is suspected, perform gallbladder diagnostic studies and follow up appropriately.

Use in Special Populations

Safety and efficacy have not been established in patients under 18 years of age.

Overdose Effects

Provide supportive treatment based on clinical signs and symptoms. Observation may be required considering the approximate 5‑day half‑life of tirzepatide.