What is the initial dose and titration schedule of tirzepatide (Mounjaro) for adults with type 2 diabetes?

Mounjaro (Tirzepatide) Dosing for Type 2 Diabetes

Initial Dose and Titration Schedule

Start tirzepatide at 2.5 mg subcutaneously once weekly for 4 weeks, then increase to 5 mg once weekly as the maintenance dose. 1

Standard Dose Escalation Protocol

• Starting dose: 2.5 mg once weekly for 4 weeks (this is a tolerability dose, not therapeutic) 1
• First maintenance dose: 5 mg once weekly after the initial 4-week period 1
• Further escalation to 10 mg: If additional glycemic control is needed, increase to 10 mg once weekly after at least 4 weeks on the 5 mg dose 1
• Maximum dose: 15 mg once weekly, achievable after at least 4 weeks on the 10 mg dose if further glycemic control is required 1

Administration Details

• Inject once weekly on the same day each week 2
• Can be given at any time of day, with or without meals 2
• Administer as a subcutaneous injection 1
• The medication has a 5-day elimination half-life, supporting once-weekly dosing 1

Critical Medication Adjustments When Starting Tirzepatide

Insulin Dose Reduction

When adding tirzepatide to existing insulin therapy, reduce the insulin dose to minimize hypoglycemia risk. 1, 3 Monitor for signs of insulin overbasalization: basal dose exceeding 0.5 units/kg/day, significant bedtime-to-morning glucose differential, or hypoglycemia occurrences. 1 Consider reducing basal insulin by 10-20% when initiating tirzepatide. 3

Sulfonylurea Management

Discontinue or reduce sulfonylurea doses by 50% when starting tirzepatide due to substantially increased hypoglycemia risk. 1 The combination of tirzepatide with sulfonylureas increases hypoglycemia risk, whereas tirzepatide as monotherapy or with metformin carries minimal hypoglycemia risk. 3

DPP-4 Inhibitor Discontinuation

Discontinue all DPP-4 inhibitors before starting tirzepatide—concurrent use provides no additional glucose-lowering benefit and is pharmacologically redundant. 1, 3

GLP-1 Receptor Agonist Contraindication

Do not combine tirzepatide with other GLP-1 receptor agonists—this is pharmacologically redundant and potentially harmful. 1 This includes medications like Soliqua (which contains lixisenatide), semaglutide, dulaglutide, or liraglutide. 3

Renal Dosing Considerations

No dose adjustment is required across all stages of chronic kidney disease, including eGFR <30 mL/min/1.73 m². 1 In fact, for patients with advanced CKD (eGFR <30 mL/min/1.73 m²), tirzepatide is actually preferred for glycemic management due to lower hypoglycemia risk and cardiovascular event reduction compared to other agents. 1

Expected Outcomes by Dose

Glycemic Control

• 5 mg dose: Mean HbA1c reduction of 2.11% 4
• 10 mg dose: Mean HbA1c reduction of 2.40% 4
• 15 mg dose: Mean HbA1c reduction of 2.34-2.8% 4, 5
• Target achievement: 85-90% of patients achieve HbA1c <7% on therapeutic doses 4

Weight Loss

• 5 mg dose: Mean weight loss of 5.4-5.8 kg (7.8% reduction) 4, 5
• 10 mg dose: Mean weight loss of 7.5-8.5 kg (11.0-12.8% reduction) 1, 4, 5
• 15 mg dose: Mean weight loss of 8.8-10.7 kg (13.9-14.7% reduction) 1, 4, 5

Common Adverse Events

The most common treatment-emergent adverse events are gastrointestinal and typically mild to moderate in severity: 6

• Nausea: 13-20% of patients 4, 5
• Diarrhea: 12-21% of patients 4
• Constipation: 14-18% of patients 5
• Vomiting: Occurs in a smaller percentage 6
• Decreased appetite: Common but percentage varies 6

These gastrointestinal effects are dose-dependent and more common at higher doses. 7 Delayed gastric emptying is a class effect that may persist with chronic use. 3

Safety Profile

Tirzepatide demonstrates a low risk of severe hypoglycemia when used as monotherapy or with metformin (RR 0.21 compared to insulin). 1 No increased risk of major adverse cardiovascular events was observed in pooled analyses, and serious adverse events occurred less frequently with tirzepatide compared to insulin (RR 0.79). 3

Common Pitfalls to Avoid

• Do not assess treatment efficacy at 4 weeks—the 2.5 mg starting dose is for tolerability only, not therapeutic effect 2
• Do not escalate doses faster than every 4 weeks—this increases gastrointestinal adverse events 1
• Do not forget to reduce insulin/sulfonylurea doses—failure to do so significantly increases hypoglycemia risk 1, 3
• Do not combine with DPP-4 inhibitors or other GLP-1 agonists—this provides no benefit and is contraindicated 1, 3