How should tirzepatide (Mounjaro) be administered to an adult with type 2 diabetes, including dosing schedule, injection technique, storage, monitoring, and contraindications?

How to Administer Mounjaro (Tirzepatide)

Mounjaro should be administered as a subcutaneous injection once weekly, starting at 2.5 mg for 4 weeks, then escalating to 5 mg, with further increases to 10 mg or 15 mg at 4-week intervals based on glycemic response and tolerability. 1, 2

Dosing Schedule

Initial and Maintenance Dosing:

• Start at 2.5 mg subcutaneously once weekly for 4 weeks (this initial dose minimizes gastrointestinal side effects) 1, 2
• Increase to 5 mg once weekly after the initial 4 weeks 1, 2
• If additional glycemic control is needed, escalate to 10 mg once weekly after at least 4 weeks on the 5 mg dose 1, 2
• Maximum dose is 15 mg once weekly, achievable after at least 4 weeks on the 10 mg dose if further control is required 1, 2

The gradual titration schedule is critical—it significantly reduces the gastrointestinal adverse events (nausea, vomiting, diarrhea) that occur in 12-31% of patients. 3 Higher doses produce greater weight loss (15% at 5 mg vs. 20.9% at 15 mg) but also higher rates of nausea (17% at 5 mg vs. 31% at 15 mg). 3

Injection Technique

Site Selection and Rotation:

• Inject into the subcutaneous tissue of the abdomen, thigh, or upper arm 4
• Avoid a 2-inch radius around the navel when using the abdomen 4
• Rotate injection sites systematically within one body area (e.g., different quadrants of the abdomen) rather than switching between different body regions with each injection 4
• Inject at least 1 cm (approximately one adult finger width) from the previous injection site, rotating in a consistent direction 4
• Change the body zone used weekly (use one quadrant or half of a zone per week) 4

Injection Procedure:

• Allow the medication to reach room temperature (leave out of refrigerator for 30-60 minutes before injection) to reduce pain and prevent lipodystrophy 4
• Ensure the skin is clean and intact; disinfect with an alcohol swab and allow it to evaporate completely 4
• Inject at a 90-degree angle for most patients 4
• Thin individuals or children may need to pinch the skin and inject at a 45-degree angle to avoid intramuscular injection 4
• Keep the needle embedded in the skin for 5 seconds after complete delivery of the dose 4
• Never inject through clothing 4

Storage Requirements

Unopened Pens/Vials:

• Store in a refrigerator at 2-8°C (36-46°F) 4
• Do not freeze or allow contamination by food 4
• Check your home refrigerator temperature, as household refrigerators commonly fall outside this range 4

Opened Pens/Vials:

• Store at ambient temperatures (15-30°C or 59-86°F) away from direct sunlight 4
• Use within the expiration date designated by the manufacturer (often 28 days for insulin products; check tirzepatide-specific labeling) 4

When Traveling:

• Use cooler packs or insulated bags if bringing medication outside in hot or cold/freezing conditions 4

Critical Medication Adjustments Before Starting

Insulin Dose Reduction:

• Reduce total daily insulin dose by approximately 20% when initiating tirzepatide to prevent hypoglycemia 1
• Monitor for signs of insulin overbasalization (basal dose >0.5 units/kg/day, significant bedtime-to-morning glucose differential, or hypoglycemia occurrences) 2

Sulfonylurea Management:

• Discontinue sulfonylureas entirely in patients with well-controlled baseline HbA1c or history of frequent hypoglycemia 1
• Alternatively, reduce sulfonylurea doses by 50% when initiating tirzepatide 2

DPP-4 Inhibitors:

• Discontinue DPP-4 inhibitors before starting tirzepatide—concurrent use provides no additional benefit 2

Other GLP-1 Receptor Agonists:

• Do not combine with other GLP-1 receptor agonists—this is pharmacologically redundant and potentially harmful 2

Diuretics:

• Stop or reduce diuretic therapy at tirzepatide initiation to prevent intravascular volume contraction and dehydration 1

Monitoring Schedule

• Monthly assessment during the first 3 months of dose escalation 3
• Evaluate efficacy at 12-16 weeks on maximum tolerated dose 3
• Consider discontinuation if less than 4-5% body weight loss at 16 weeks on maximum tolerated dose 3
• Quarterly monitoring after reaching maintenance dose 3
• Watch for cardiac arrhythmias/tachycardia; consider beta blockers if symptomatic 3

Contraindications

Absolute Contraindications (per American College of Cardiology):

• Personal or family history of medullary thyroid cancer 1
• Multiple endocrine neoplasia type 2 (MEN2) 1
• History of serious hypersensitivity reaction to tirzepatide 1

Use with Caution:

• Clinically meaningful gastroparesis 1
• Prior gastric surgery, including bariatric surgery 1
• Pregnancy or breastfeeding 1

Perioperative Management

Critical Timing:

• Discontinue tirzepatide at least 3 days before any planned surgery due to delayed gastric emptying, which increases aspiration risk during anesthesia 1

Special Populations

Renal Impairment:

• No dosage adjustments required across all stages of chronic kidney disease, including eGFR <30 mL/min/1.73 m² 1, 2
• Tirzepatide is actually preferred for patients with eGFR <30 mL/min/1.73 m² due to superior glycemic efficacy and lower hypoglycemia risk compared to other agents 2

Common Adverse Effects and Management

Gastrointestinal Effects:

• Nausea (13-31%), diarrhea (12-23%), vomiting (12%), constipation (12-18%), decreased appetite (10-12%) are the most common adverse events 3
• These are generally mild-to-moderate and most pronounced during the first 20 weeks of dose escalation 3
• Maintain adequate hydration, especially when nausea is accompanied by vomiting or diarrhea 3
• Consider slowing dose escalation or maintaining the current dose longer if nausea is severe or persistent 3

Hypoglycemia:

• Tirzepatide does not differ from usual care for severe hypoglycemia (RR 1.32, CI 0.78-2.22) when used without insulin or sulfonylureas 3
• Risk is significantly reduced compared to insulin (RR 0.21) 2

Serious Adverse Events:

• Tirzepatide does not differ from usual care for serious adverse events (RR 0.79, CI 0.51-1.22; high certainty of evidence) 3

Critical Drug Interactions

Oral Contraceptives:

• Advise non-oral contraception or addition of a non-oral method for 4 weeks after each dose escalation due to delayed gastric emptying affecting absorption 3

Narrow Therapeutic Index Medications:

• Monitor warfarin closely due to potential delayed absorption 3

Common Pitfalls to Avoid

• Incorrect dose administration is the most frequently reported adverse event, increasing 8-fold from 2022 to 2024 5
• Never remove insulin from prefilled pens using a syringe to fill another device—this can cause insulin concentration differences 4
• Do not inject into areas of lipodystrophy (lumps or indentations in the skin from repeated injections in the same spot) 4
• Failure to adjust insulin or sulfonylurea therapy when starting tirzepatide significantly increases hypoglycemia risk, especially in elderly individuals 1
• Do not increase dosing frequency beyond once weekly—this would increase gastrointestinal adverse effects without additional benefit 1