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 modified peptide with a fatty acid side chain that binds albumin and prolongs half‑life. It activates both GIP and GLP‑1 receptors, enhancing insulin secretion and reducing glucagon in a glucose‑dependent manner.

Dosage & Administration

Route: Subcutaneous injection.
Starting dose: 2.5 mg once weekly (initiation only, not for glycemic control).
After 4 weeks: Increase to 5 mg once weekly.
Further titration: Increase by 2.5 mg increments after ≥4 weeks, up to maximum 15 mg once weekly.
Missed dose: Take 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; administer separately.

Interactions

Risk of hypoglycemia with insulin or sulfonylureas → dose reduction may be needed.
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 Common: Nausea, diarrhea, decreased appetite, vomiting, constipation, dyspepsia, abdominal pain.

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

Precautions & Warnings

Counsel patients on thyroid tumor risk.
Monitor for pancreatitis; discontinue if suspected.
Reduce insulin/secretagogue dose to lower hypoglycemia risk.
Monitor renal function in patients with severe GI 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 symptoms. Observation may be required due to ~5‑day half‑life.