How should Mounjaro (tirzepatide) injections be used in a patient with type 2 diabetes?

How to Use Mounjaro (Tirzepatide) Injections

Starting Dose and Titration Schedule

Mounjaro should be initiated at 2.5 mg subcutaneously once weekly, then increased by 2.5 mg every 4 weeks until the target maintenance dose is reached. 1, 2

• Initial dose: 2.5 mg once weekly for 4 weeks 1
• Titration schedule: Increase by 2.5 mg increments every 4 weeks 1, 3
• Maintenance doses: 5 mg, 10 mg, or 15 mg once weekly depending on glycemic response and tolerability 1, 3
• The gradual up-titration reduces gastrointestinal side effects, particularly nausea and vomiting 4, 1

Administration Technique

• Inject subcutaneously in the abdomen, thigh, or upper arm 4
• Administer once weekly on the same day each week, at any time of day, with or without meals 1
• Rotate injection sites within the same region (e.g., different areas of the abdomen) rather than switching between body regions to minimize absorption variability 4
• Available as single-dose prefilled pens and single-dose vials 1

When to Use Mounjaro in the Treatment Algorithm

For patients with type 2 diabetes requiring injectable therapy, GLP-1 receptor agonists (including dual GIP/GLP-1 agonists like tirzepatide) are preferred over insulin due to superior weight loss, lower hypoglycemia risk, and comparable or better glycemic control. 4

• Consider tirzepatide when oral medications (particularly metformin-based regimens) fail to achieve HbA1c targets 4
• Tirzepatide is preferred over insulin for patients needing injectable therapy, unless severe symptomatic hyperglycemia or catabolic features are present 4
• Continue metformin unless contraindicated when starting tirzepatide 4

Expected Outcomes

Tirzepatide produces unprecedented reductions in HbA1c (1.24-2.58%) and body weight (5.4-11.7 kg) compared to other single agents. 5

• 23-62% of patients achieve HbA1c <5.7% (normoglycemia range) 5
• 21-68% of patients lose >10% of baseline body weight 5
• Tirzepatide 10-15 mg produces greater HbA1c reduction than semaglutide 1 mg (-0.39 to -0.45 percentage points difference) 6
• Weight loss is 1.9-5.5 kg greater than with semaglutide 6

Combination with Insulin

If additional glucose lowering is needed despite tirzepatide therapy, basal insulin can be added, and insulin doses should be reduced when initiating or escalating tirzepatide. 4

• When adding tirzepatide to existing insulin therapy, reduce insulin dose by 10-20% to prevent hypoglycemia 4
• In the SURPASS-5 trial, tirzepatide added to insulin glargine reduced HbA1c by an additional 1.24-1.53% compared to placebo 3
• The combination provides superior glycemic control while allowing insulin dose reduction 4, 3

Managing Side Effects

Gastrointestinal side effects are the most common adverse events and are typically mild to moderate, occurring most frequently during dose escalation. 1, 5

• Most common: Nausea (13-22%), diarrhea (12-21%), vomiting (6-10%), decreased appetite 1, 6
• These effects are usually transient and diminish with continued use 4
• The slow titration schedule (2.5 mg increases every 4 weeks) minimizes GI symptoms 4, 1
• If intolerable side effects occur, consider slowing the titration or maintaining a lower dose 4

Critical Contraindications and Precautions

• Contraindicated: Personal or family history of medullary thyroid cancer, multiple endocrine neoplasia type 2 (MEN2) 4
• Discontinue immediately if pancreatitis is suspected; do not restart if confirmed 4
• Use caution in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²) 4
• Hypoglycemia risk increases when combined with insulin or sulfonylureas—reduce doses of these agents when starting tirzepatide 4

Monitoring Requirements

• Check HbA1c every 3 months during titration to assess glycemic response 4
• Monitor for gastrointestinal symptoms, particularly during dose escalation 1
• Assess for hypoglycemia if combined with insulin or sulfonylureas 4
• Monitor weight and adjust other weight-affecting medications accordingly 4

Common Pitfalls to Avoid

• Never skip the initial 2.5 mg starting dose—this loading dose is essential for tolerability 1
• Do not escalate faster than every 4 weeks—premature dose increases significantly worsen GI side effects 4, 1
• Do not discontinue metformin when starting tirzepatide unless contraindicated 4
• Reduce insulin doses by 10-20% when adding tirzepatide to prevent hypoglycemia 4
• Do not delay tirzepatide initiation in favor of continuing to escalate basal insulin beyond 0.5 units/kg/day—add tirzepatide instead 4