What are the guidelines for ordering Mounjaro (tirzepatide) for an adult patient with type 2 diabetes, considering their renal function, medical history, and potential side effects?

Guidelines for Ordering Mounjaro (Tirzepatide)

Start Mounjaro at 2.5 mg subcutaneously once weekly for 4 weeks, then increase to 5 mg once weekly, with further escalation to 10 mg or 15 mg at 4-week intervals based on glycemic response and tolerability. 1

Initial Dosing Protocol

• Begin with 2.5 mg subcutaneously once weekly for the first 4 weeks as the starting dose 1
• Increase to 5 mg once weekly after the initial 4-week period 1
• Escalate to 10 mg once weekly if additional glycemic control is needed, after at least 4 weeks on the 5 mg dose 1
• Further increase to 15 mg once weekly for maximum glycemic control, after at least 4 weeks on the 10 mg dose 1

This gradual titration schedule minimizes gastrointestinal side effects, which occur in 12-22% of patients on standard weekly dosing 1. The most common adverse events are nausea (13-18%), diarrhea (12-21%), decreased appetite, and vomiting, which are typically mild to moderate in severity 2, 3.

Patient Selection and Positioning in Treatment Algorithm

Mounjaro should be considered as a second-line agent after metformin, particularly for patients with cardiovascular disease, heart failure, or chronic kidney disease. 4

When to Prioritize Mounjaro (GLP-1 RA Class):

• Patients with established atherosclerotic cardiovascular disease or high cardiovascular risk 5
• Patients requiring significant weight loss (achieves >5% weight loss in most patients) 4
• Patients with stroke risk (reduces stroke by 12-26%) 4
• Patients with eGFR <30 ml/min per 1.73 m² or advanced CKD, where GLP-1 RAs are preferred over other agents due to lower hypoglycemia risk 5, 6
• Patients who have not achieved glycemic targets despite metformin and SGLT2 inhibitor use, or who cannot use those medications 5

Complementary Therapy:

• SGLT2 inhibitors or metformin should be used as complementary agents rather than increasing Mounjaro dosing frequency 1
• Early combination therapy with metformin plus Mounjaro can be considered at treatment initiation to shorten time to glycemic goals 4

Renal Function Considerations

No dosage adjustments are required based on renal function, which is a significant advantage over many other antidiabetic medications. 1

• Mounjaro can be used without dose adjustment in patients with normal renal function or mild to moderate renal impairment 1
• For patients with eGFR <30 ml/min per 1.73 m² or on dialysis, GLP-1 RAs like Mounjaro are preferred over sulfonylureas or insulin due to lower hypoglycemia risk 5, 6
• No specific monitoring of renal function is required for Mounjaro dosing adjustments 1

Medication Adjustments to Prevent Hypoglycemia

Reduce or discontinue insulin or insulin secretagogues (sulfonylureas) when initiating Mounjaro to minimize hypoglycemia risk. 1, 4

• For patients taking insulin or sulfonylureas and currently meeting glycemic targets, consider stopping or reducing the dose of these medications before adding Mounjaro 5, 1
• When adding SGLT2 inhibitors to patients already on Mounjaro, no adjustment to Mounjaro is needed, but reduce or discontinue any sulfonylureas 6
• The risk of clinically significant or severe hypoglycemia with Mounjaro alone is low 2

Absolute Contraindications

Do not prescribe Mounjaro in patients with:

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

Relative Contraindications and Cautions

Use Mounjaro with caution in:

• Clinically meaningful gastroparesis 1
• Prior gastric surgery, including bariatric surgery 1
• Pregnancy or breastfeeding 1
• Perioperative settings: Withhold Mounjaro during prolonged fasting, surgery, or critical medical illness due to delayed gastric emptying and increased aspiration risk 5, 1

Monitoring and Follow-Up

• Reevaluate medication plans every 3-6 months, adjusting based on glycemic control, weight goals, and metabolic comorbidities 4
• Monitor for gastrointestinal symptoms during dose escalation, which can be minimized by the gradual titration schedule 1
• Target HbA1c should be between 7-8% for most adults, with deintensification if HbA1c falls below 6.5% 4
• In clinical trials, 85-90% of patients achieved HbA1c <7% with Mounjaro 3

Clinical Efficacy Expectations

Mounjaro demonstrates superior glycemic control and weight loss compared to other GLP-1 RAs and insulin:

• HbA1c reductions of 1.87-2.59% across clinical trials 7
• Weight loss of 5.4-11.7 kg (with 20.7-68.4% of patients losing >10% of baseline body weight) 8
• 23-62% of patients achieved HbA1c <5.7% (normoglycemia range) 8
• Superior to semaglutide 1 mg weekly for both glycemic control and weight loss 2, 8

Common Pitfalls to Avoid

• Do not increase dosing frequency beyond once weekly – this increases gastrointestinal adverse effects without additional benefit 1
• Do not skip the initial 2.5 mg starting dose – this increases the risk of nausea and vomiting 1
• Do not continue sulfonylureas or high-dose insulin without dose reduction when adding Mounjaro, as this significantly increases hypoglycemia risk 1, 4
• Do not withhold Mounjaro solely due to a reversible decrease in eGFR after initiation, as this is expected and generally not an indication to discontinue 5