Indications

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

Pharmacology Tirzepatide is a 39‑amino‑acid peptide with a fatty acid moiety enabling albumin binding and prolonged half‑life. It selectively binds and activates both GIP and GLP‑1 receptors, enhancing insulin secretion and reducing glucagon levels in a glucose‑dependent manner.

Dosage & Administration

Route: Subcutaneous injection.
Starting dose: 2.5 mg once weekly (for initiation, not glycemic control).
After 4 weeks: Increase to 5 mg once weekly.
Further titration: Increase by 2.5 mg increments after ≥4 weeks on current dose, up to maximum 15 mg once weekly.
Missed dose: Administer within 4 days; if >4 days, skip and resume on next scheduled day.
Injection sites: Abdomen, thigh, or upper arm. Rotate sites. Do not mix with insulin; separate injections are required.

Interactions

May increase risk of hypoglycemia with insulin or sulfonylureas → consider dose reduction.
Delays gastric emptying → may affect absorption of oral drugs with narrow therapeutic index (e.g., warfarin).
Oral contraceptives: Use non‑oral or barrier method for 4 weeks after initiation and after each dose escalation.

Contraindications

Hypersensitivity to tirzepatide or components.
Personal/family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2).

Side Effects Most common: Nausea, diarrhea, decreased appetite, vomiting, constipation, dyspepsia, abdominal pain.

Pregnancy & Lactation Use only if potential benefit justifies risk. Consider maternal glycemic control, breastfeeding benefits, and possible adverse effects on infant.

Precautions & Warnings

Counsel patients on risk of thyroid tumors (MTC).
Monitor for pancreatitis; discontinue if suspected.
Reduce dose of insulin or secretagogues to lower hypoglycemia risk.
Monitor renal function in patients with severe GI adverse reactions.
Monitor diabetic retinopathy progression.
Evaluate gallbladder if cholelithiasis suspected.

Use in Special Populations Safety and efficacy not established in patients <18 years.

Overdose Effects Supportive treatment based on clinical signs and symptoms. Observation may be required due to ~5‑day half‑life.