Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1 Trial)
Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A
New England Journal of Medicine · Vol. 387(3) · pp. 205–216 · 2022
Phase 3 RCT demonstrating that tirzepatide (dual GIP/GLP-1 receptor agonist) achieves up to 22.5% mean body weight reduction — the highest ever recorded for a pharmacological weight loss agent. Establishes dual incretin therapy as superior to single GLP-1 agonism for obesity treatment.
Key Findings
Mean weight reduction of 20.9% (10 mg) and 22.5% (15 mg) at 72 weeks vs. 2.4% placebo
91% of participants achieved ≥5% weight loss at highest dose
Significant improvements in all cardiometabolic risk factors
Dual GIP + GLP-1 receptor agonism superior to GLP-1 alone for weight loss
Adverse effect profile similar to GLP-1 agonists; predominantly GI and transient
Methodology
Phase 3 double-blind RCT. 2539 adults with obesity or overweight with comorbidities. 72-week treatment with lifestyle counseling in both arms.
Limitations
Weight regain after discontinuation expected. Long-term cardiovascular outcomes trial ongoing. High cost limits access.
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