What are the recommendations for implementing the Surmount trial's findings into clinical practice?

Implementing SURMOUNT Trial Findings into Clinical Practice

Tirzepatide should be offered to adults with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with weight-related complications, excluding diabetes, as a once-weekly subcutaneous injection at maximum tolerated doses (10 mg or 15 mg) for sustained weight reduction and cardiovascular risk mitigation. 1, 2

Patient Selection Criteria

Eligible patients include:

• Adults aged ≥40 years with BMI ≥27 kg/m² 1
• Those with established cardiovascular disease OR multiple cardiovascular risk factors 1
• Patients with prediabetes who require diabetes prevention 3
• Individuals without type 2 diabetes (critical exclusion criterion) 1, 2

The SURMOUNT-MMO trial specifically targets this population to assess a five-component composite outcome: nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, heart failure events, or death from any cause 1. This represents the first incretin medication outcome trial addressing both primary and secondary cardiovascular disease prevention 1.

Dosing and Administration Protocol

Initiate tirzepatide with dose escalation over 20 weeks:

• Start at 2.5 mg weekly, escalating to maximum tolerated dose of 10 mg or 15 mg 2
• Continue treatment for minimum 72 weeks for substantial weight reduction 2
• Extended treatment up to 176 weeks provides sustained benefits and diabetes prevention 3

The dose-escalation period is critical for minimizing gastrointestinal adverse events, which are most common during the first 20 weeks 2, 3.

Expected Clinical Outcomes

Weight reduction targets at 72 weeks:

• 5 mg dose: -15.0% mean weight loss, with 85% achieving ≥5% reduction 2
• 10 mg dose: -19.5% mean weight loss, with 89% achieving ≥5% reduction and 50% achieving ≥20% reduction 2
• 15 mg dose: -20.9% mean weight loss, with 91% achieving ≥5% reduction and 57% achieving ≥20% reduction 2

Diabetes prevention efficacy:

• At 176 weeks, only 1.3% of tirzepatide-treated patients developed type 2 diabetes versus 13.3% with placebo (hazard ratio 0.07) 3
• Even after 17 weeks off-treatment, diabetes incidence remained significantly lower (2.4% vs 13.7%, hazard ratio 0.12) 3

Comparative Effectiveness

When choosing between tirzepatide and semaglutide:

• Tirzepatide demonstrates superior weight reduction: -20.2% versus -13.7% with semaglutide at 72 weeks 4
• Waist circumference reduction is greater: -18.4 cm versus -13.0 cm with semaglutide 4
• More patients achieve ≥10%, ≥15%, ≥20%, and ≥25% weight reduction thresholds with tirzepatide 4

This head-to-head comparison establishes tirzepatide as the preferred agent when maximum weight reduction is the therapeutic goal 4.

Quality of Life Considerations

Prioritize tirzepatide in patients with:

• Physical function limitations at baseline, who show greater HRQoL improvements 5
• Need for improvements in both physical and mental health domains 5
• Weight-related psychological and social dysfunction 5

Quality of life improvements are generally larger in patients achieving greater weight reduction thresholds, with dose-dependent benefits 5.

Safety Monitoring and Adverse Event Management

Gastrointestinal adverse events are most common:

• Occur primarily during dose escalation (first 20 weeks) 2, 3
• Most are mild to moderate in severity 2, 3
• Treatment discontinuation rates: 4.3% (5 mg), 7.1% (10 mg), 6.2% (15 mg) versus 2.6% with placebo 2

Critical safety considerations:

• No new safety signals identified in 3-year follow-up 3
• Cardiometabolic measures show consistent improvement across all doses 2
• Monitor for gastrointestinal symptoms and adjust dose escalation timing if needed 2

Long-Term Treatment Strategy

Maintain treatment for extended duration:

• Initial 72-week treatment provides substantial weight reduction 2
• Extended 176-week treatment maximizes diabetes prevention and sustained weight loss 3
• Treatment interruption results in some weight regain, though diabetes prevention persists 3

The SURMOUNT-MMO trial's event-driven design will provide definitive evidence on cardiovascular morbidity and mortality outcomes, enrolling approximately 15,000 participants across 664 sites in 27 countries 1.

Implementation Pitfalls to Avoid

Do not:

• Prescribe tirzepatide to patients with type 2 diabetes (different indication and trial population) 1, 2
• Discontinue treatment prematurely before 72 weeks without medical necessity 2
• Escalate doses too rapidly, increasing gastrointestinal adverse events 2
• Ignore physical function limitations at baseline, which predict greater QoL benefit 5

Do:

• Use maximum tolerated dose (10 mg or 15 mg) for optimal outcomes 2, 4
• Continue treatment long-term for sustained diabetes prevention 3
• Monitor cardiovascular risk factors as part of comprehensive obesity management 1
• Assess and document quality of life improvements to justify continued therapy 5