SURMOUNT-1

Population

• 2539 adults with BMI of 30 or more, or 27 or more and at least one weight-related complication, excluding diabetes.
• At baseline, mean body weight was 104.8 kg, mean BMI was 38.0, and 94.5% of participants had a BMI of 30 or higher.

Intervention

Once-weekly subcutaneous tirzepatide 5 mg, 10 mg, or 15 mg for 72 weeks, including a 20-week dose-escalation period (1:1:1:1 assignment).

Comparator

Placebo.

Key results

• Coprimary percentage change at week 72: mean change -15.0% (95% CI -15.9 to -14.2) with 5 mg, -19.5% (95% CI -20.4 to -18.5) with 10 mg, and -20.9% (95% CI -21.8 to -19.9) with 15 mg, versus -3.1% (95% CI -4.3 to -1.9) with placebo (P<0.001 for all comparisons with placebo).
• Coprimary 5% responder: weight reduction of 5% or more in 85% (95% CI 82-89) with 5 mg, 89% (95% CI 86-92) with 10 mg, and 91% (95% CI 88-94) with 15 mg, versus 35% (95% CI 30-39) with placebo.
• Additional 20% threshold, not coprimary: 50% (95% CI 46-54) with 10 mg and 57% (95% CI 53-61) with 15 mg had a 20% or greater weight reduction, versus 3% (95% CI 1-5) with placebo (P<0.001 for all comparisons with placebo).
• Improvements in all prespecified cardiometabolic measures were observed with tirzepatide; the abstract does not give numeric effect sizes for those measures.

Harms

• The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation.
• Adverse events caused treatment discontinuation in 4.3%, 7.1%, and 6.2% of participants receiving 5 mg, 10 mg, and 15 mg tirzepatide, and in 2.6% receiving placebo.

Practice impact

• Offer weekly tirzepatide when the goal is substantial weight loss in adults without diabetes who meet these BMI criteria; higher doses produced larger mean percent weight loss.

Applicability

• Adults with BMI of 30 or higher, or 27 or higher plus at least one weight-related complication, excluding diabetes.
• Most participants already had BMI of 30 or higher (94.5%).

Limitations

• This is a weight-loss trial, not a cardiovascular-outcomes trial.
• The 20% responder rates are additional results, not coprimary end points.
• Cardiometabolic improvements are described without numeric estimates.

Common misinterpretations

• Do not quote only one dose or only the 5% responder rate as the sole primary result; both coprimary end points were tested at 5, 10, and 15 mg.
• These participants did not have diabetes; do not treat this as a glycemic-control trial.