What is the maximum recommended dose of Zepbound (tirzepatide)?

Maximum Recommended Dose of Zepbound (Tirzepatide)

The maximum recommended dose of Zepbound (tirzepatide) is 15 mg administered once weekly by subcutaneous injection. 1, 2

Dosing Information

• Tirzepatide (Zepbound) is available in three maintenance dose strengths: 5 mg, 10 mg, and 15 mg for weekly subcutaneous administration 1, 2
• The 15 mg dose provides maximum efficacy with 20.9% weight loss at 72 weeks in patients with obesity, compared to 19.5% with 10 mg and 15.0% with 5 mg 1, 2
• Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, providing enhanced weight loss compared to GLP-1 receptor agonists alone 1, 3

Dose Escalation Protocol

• Tirzepatide treatment should be initiated at a lower dose and gradually escalated to minimize gastrointestinal side effects 2, 4
• The recommended dose escalation strategy is:
  • Start at 2.5 mg once weekly
  • Increase by 2.5 mg every 4 weeks until the target maintenance dose is reached 2, 4
• The full 15 mg dose should only be reached after appropriate dose escalation to minimize adverse effects 2, 4, 5

Efficacy Considerations

• At 15 mg weekly, tirzepatide demonstrates superior weight reduction compared to lower doses:
  • 15 mg: 20.9% weight loss
  • 10 mg: 19.5% weight loss
  • 5 mg: 15.0% weight loss 1
• In patients with type 2 diabetes, tirzepatide 15 mg provides greater HbA1c reduction (-2.37%) compared to insulin degludec (-1.34%) 4
• Tirzepatide 15 mg is associated with statistically significant greater improvements in cardiometabolic risk factors compared to semaglutide 2.4 mg, including waist circumference, fasting plasma glucose, and triglycerides 6

Safety Considerations

• The most common adverse events with tirzepatide are gastrointestinal in nature, including:
  • Nausea (13-18%)
  • Diarrhea (15-17%)
  • Decreased appetite (6-12%)
  • Vomiting (6-10%) 4, 2
• Gastrointestinal side effects are typically mild to moderate and decrease over time 4
• The incidence of hypoglycemia with tirzepatide is low (1-2%) compared to insulin-based therapies 4
• For patients using oral hormonal contraception, advise using or adding a non-oral contraception method for 4 weeks after initiation and dose escalations 2

Special Populations

• No dose adjustment is necessary for patients with mild to moderate renal impairment 2
• Use caution in people with kidney disease when initiating or increasing dose due to potential risk of acute kidney injury 1
• Monitor for potential consequences of delayed absorption of oral medications with narrow therapeutic indices due to tirzepatide's effect on gastric emptying 1, 2

Clinical Monitoring

• Assess effectiveness and safety at least monthly for the first 3 months and at least quarterly thereafter 2
• Monitor for gastrointestinal side effects, which are the most common adverse events but typically decrease over time 2, 4
• Be aware of potential gallbladder-related complications and gastrointestinal disorders (severe constipation and small bowel obstruction/ileus) 1