What is the recommended dosing for tirzepatide (a dual GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist) in adults with type 2 diabetes?

Tirzepatide Dosing for Type 2 Diabetes

Start tirzepatide at 2.5 mg subcutaneously once weekly for 4 weeks, then increase to 5 mg once weekly as the maintenance dose, with further titration to 10 mg or 15 mg weekly if additional glycemic control is needed after at least 4 weeks at each dose level. 1

Initial Dose and Titration Schedule

• Begin with 2.5 mg subcutaneously once weekly for the first 4 weeks as the initial titration dose 1
• Increase to 5 mg once weekly after 4 weeks for maintenance dosing 1
• Titrate to 10 mg once weekly if additional glycemic control is required, but only after at least 4 weeks on the 5 mg dose 1
• The maximum dose is 15 mg once weekly, achieved after at least 4 weeks on the 10 mg dose if further glycemic control is needed 1

Expected Outcomes by Dose

• The 10 mg weekly dose produces approximately 12.8% weight loss from baseline 1
• The 15 mg weekly dose achieves 14.7% weight loss 1
• Tirzepatide reduces HbA1c by 1.87-2.59% across the dose range 2
• 23.0-62.4% of patients achieve HbA1c <5.7% (normal range) with tirzepatide 3

Administration Details

• Administer as a once-weekly subcutaneous injection 4, 5
• Available as single-dose prefilled pens and single-dose vials 5
• The medication has an elimination half-life of 5 days 4

Critical Dosing Considerations When Combined with Other Medications

• When adding tirzepatide to existing insulin therapy, reduce insulin dosing by approximately 20% to minimize hypoglycemia risk 1
• Discontinue or reduce sulfonylurea doses by 50% when initiating tirzepatide due to increased hypoglycemia risk 4
• Discontinue DPP-4 inhibitors before starting tirzepatide, as concurrent use provides no additional benefit 4
• Tirzepatide reduces severe hypoglycemia compared to insulin (RR 0.21) 1

Monitoring and Dose Adjustment

• Evaluate treatment response at 12-16 weeks on the maximum tolerated therapeutic dose 1
• If weight loss is <5% after 3 months at therapeutic dose, consider discontinuation and alternative approaches 1
• Assess patients every 4 weeks during titration for gastrointestinal tolerance and adverse effects 1
• Monitor quarterly after reaching maintenance dose for weight stability, cardiovascular risk factors, and medication tolerance 1

Common Pitfalls to Avoid

• Do not skip the 2.5 mg initial dose—starting at higher doses significantly increases gastrointestinal adverse events 1, 5
• Do not advance doses more frequently than every 4 weeks—this increases nausea, vomiting, and diarrhea 5, 2
• Do not combine with other GLP-1 receptor agonists—this is pharmacologically redundant and potentially harmful 4
• Do not use in patients with personal or family history of medullary thyroid cancer or MEN2 syndrome—this is an absolute contraindication 1, 5

Renal Dosing

• No dose adjustment is required across all stages of CKD, including eGFR <30 mL/min/1.73 m² 4