What dose of Mounjaro (tirzepatide) should be initiated for a patient considering weight loss, who was previously discussed to be on a trial of Ozempic (semaglutide)?

Initial Dosing of Mounjaro (Tirzepatide) for Weight Loss

For a patient considering weight loss who was previously discussed for Ozempic (semaglutide), Mounjaro (tirzepatide) should be initiated at 2.5 mg subcutaneously once weekly, with gradual dose titration every 4 weeks to minimize gastrointestinal side effects.

Dosing Protocol for Tirzepatide (Mounjaro)

Tirzepatide is a dual GIP/GLP-1 receptor agonist that offers superior weight loss compared to semaglutide. The recommended titration schedule is:

• Start at 2.5 mg subcutaneously once weekly for 4 weeks
• Increase to 5 mg once weekly for 4 weeks
• Increase to 7.5 mg once weekly for 4 weeks
• Increase to 10 mg once weekly for 4 weeks
• Increase to 12.5 mg once weekly for 4 weeks (if needed)
• Maximum dose: 15 mg once weekly

Rationale for Tirzepatide Selection

Tirzepatide has demonstrated superior efficacy compared to semaglutide for weight loss:

• Tirzepatide produces mean weight loss of 20.2% compared to 13.7% with semaglutide at 72 weeks 1
• Tirzepatide shows greater reductions in waist circumference (-18.4 cm vs -13.0 cm) 1
• More patients achieve clinically significant weight loss thresholds (10%, 15%, 20%, and 25% of body weight) with tirzepatide than semaglutide 1

Side Effect Profile and Management

The most common adverse effects are gastrointestinal in nature, similar to semaglutide but potentially more pronounced:

• Nausea (10-31%)
• Diarrhea (7-23%)
• Vomiting (2-12%)
• Constipation (3-5%)
• Abdominal pain (3-5%)
• Alopecia (1-6%) 2

Management of Side Effects:

• Slow titration is essential to minimize GI side effects
• Ensure adequate hydration, especially if taking insulin or sulfonylureas
• Most side effects are mild to moderate and occur primarily during dose escalation
• Side effects typically improve with continued use

Monitoring Recommendations

• Assess efficacy and safety monthly for the first 3 months, then quarterly
• Early response (>5% weight loss after 3 months) predicts long-term success 2
• Consider discontinuing if <5% weight loss after 3 months at maximum tolerated dose 2
• Monitor for signs of pancreatitis or gallbladder disease
• No dose adjustment needed for mild to moderate renal impairment 2

Important Precautions

• Contraindicated in patients with personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia type 2 2
• Use caution in patients with a history of pancreatitis
• Not recommended for use during pregnancy or breastfeeding
• Do not use concurrently with other GLP-1 receptor agonists or DPP-4 inhibitors 2
• May delay gastric emptying, potentially affecting absorption of other medications

Clinical Pearls

• If more than 2 consecutive doses are missed, consider lowering the next dose if tolerability was an issue
• If 3 or more consecutive doses are missed, restart the titration schedule 2
• Some patients may achieve good results at submaximal doses and can continue at that level
• Tirzepatide improves insulin sensitivity and secretory responses to a greater extent than semaglutide 3
• Tirzepatide has demonstrated cardiovascular safety in clinical trials 3

By following this structured titration approach and monitoring protocol, you can maximize the weight loss benefits of tirzepatide while minimizing adverse effects.