Tirzepatide Once Weekly for the Treatment of Obesity

The SURMOUNT-1 trial, published in the New England Journal of Medicine, was a phase 3, randomized, double-blind, placebo-controlled study that evaluated tirzepatide in 2,539 adults with BMI ≥30 (or ≥27 with comorbidity) without type 2 diabetes. Participants were randomized to tirzepatide 5 mg, 10 mg, 15 mg, or weekly placebo for 72 weeks, with lifestyle intervention.

The results were the most impressive ever reported for a pharmacological obesity treatment: mean weight loss was -16.0% (5 mg), -21.4% (10 mg), and -22.5% (15 mg), compared to only -2.4% with placebo. All comparisons were highly significant (p<0.001).

• 96% of participants on tirzepatide 15 mg achieved ≥5% weight loss
• 63% achieved ≥20% loss, a threshold previously considered achievable only with bariatric surgery
• Significant improvements were observed in waist circumference, blood pressure, and lipid profile
• The most common adverse events were gastrointestinal (nausea, diarrhea), predominantly mild to moderate

SURMOUNT-1 represented a turning point in pharmacological obesity treatment, demonstrating that tirzepatide produces weight loss comparable to or greater than surgical procedures. Dual GIP/GLP-1 agonism established itself as the most effective pharmacological strategy available for obesity, leading to the approval of tirzepatide (Zepbound) for this indication.