What is the recommended dose of Tirzepitide (a dual GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist) for the treatment of type 2 diabetes?

Tirzepatide Dosing for Type 2 Diabetes

The recommended maintenance dosage of tirzepatide for type 2 diabetes is 5 mg, 10 mg, or 15 mg injected subcutaneously once weekly, with a maximum dosage of 15 mg once weekly. 1

Initial Dosing and Titration

• Start with 2.5 mg subcutaneously once weekly for 4 weeks (note: this is for treatment initiation only and not approved as a maintenance dose) 1
• After 4 weeks, increase to 5 mg once weekly 1
• Dose may be increased in 2.5 mg increments after at least 4 weeks on the current dose 1
• Consider treatment response and tolerability when selecting the maintenance dosage 1
• If patients don't tolerate a maintenance dosage, consider a lower maintenance dosage 1

Efficacy Considerations

• Tirzepatide demonstrates dose-dependent glycemic control and weight reduction benefits 2
• At 10 mg weekly, tirzepatide achieves approximately 12.8% weight loss from baseline 2
• At 15 mg weekly, tirzepatide achieves approximately 14.7% weight loss from baseline 2
• Tirzepatide shows superior HbA1c reduction compared to semaglutide and insulin-based therapies 3, 4
• Tirzepatide reduces severe hypoglycemia compared to insulin (RR, 0.21 [CI, 0.11 to 0.38]) 2

Administration Guidelines

• Administer subcutaneously in the abdomen, thigh, or upper arm 1
• Rotate injection sites with each dose 1
• Can be administered at any time of day, with or without meals 1
• If a dose is missed, administer as soon as possible within 4 days (96 hours) after the missed dose 1
• If more than 4 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day 1

Safety Considerations

• Most common adverse events are gastrointestinal in nature (nausea, vomiting, diarrhea, esophageal reflux) 2, 3
• Monitor for potential consequences of delayed absorption of oral medications 2
• Use caution in people with kidney disease when initiating or increasing dose due to potential risk of acute kidney injury 2
• May cause cholelithiasis and gallstone-related complications 2
• Black box warning: Risk of thyroid C-cell tumors in rodents; human relevance not determined 1
• Contraindicated in patients with personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 1

Special Considerations

• Advise patients using oral hormonal contraception to use or add a non-oral contraception method for 4 weeks after initiation and dose escalations 2
• Monitor effects of oral medications with narrow therapeutic index (warfarin) or whose efficacy is dependent on threshold concentration 2
• When adding tirzepatide to insulin therapy, insulin dosing should be reassessed to minimize hypoglycemia risk 2
• Consider cost and access factors when prescribing; tirzepatide has a median AWP of $1,228 for a 15 mg pen 2

Clinical Pearls

• Tirzepatide has the highest weight loss efficacy among agents approved for glycemic management 2
• Consider tirzepatide over insulin when possible, as it offers greater glycemic effectiveness with beneficial effects on weight and hypoglycemia risk 2
• For patients with cost barriers, consider other options as tirzepatide is relatively expensive compared to older diabetes medications 2
• Gastrointestinal side effects can be mitigated by following the recommended dose escalation schedule 1, 3