Tirzepatide Once Weekly for the Treatment of Obesity.
Level 2 - randomized trial
Phase 3 double-blind randomized controlled trial
PubMed 35658024 · doi:10.1056/NEJMoa2206038
What was done
A phase 3, double-blind, randomized controlled trial (SURMOUNT-1) evaluated once-weekly subcutaneous tirzepatide at doses of 5 mg, 10 mg, or 15 mg compared with placebo over 72 weeks, including a 20-week dose-escalation period. The trial enrolled 2,539 adults with a BMI of 30 or higher, or a BMI of 27 or higher with at least one weight-related complication, excluding individuals with diabetes. Coprimary endpoints were the percentage change in body weight from baseline to week 72 and the proportion of participants achieving a body weight reduction of 5% or more, evaluated using a treatment-regimen estimand in the intention-to-treat population.
What was found
Mean baseline body weight was 104.8 kg and mean BMI was 38.0. At week 72, the mean percentage change in body weight was -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 of tirzepatide, compared with -3.1% (95% CI, -4.3 to -1.9) with placebo (P<0.001 for all doses versus placebo). A weight reduction of 5% or more occurred in 85% (5 mg), 89% (10 mg), and 91% (15 mg) of tirzepatide participants versus 35% with placebo. A weight reduction of 20% or more was reached by 50% (10 mg) and 57% (15 mg) versus 3% with placebo. Gastrointestinal adverse events were the most frequent, occurred primarily during dose escalation, and led to treatment discontinuation in 4.3% (5 mg), 7.1% (10 mg), 6.2% (15 mg), and 2.6% (placebo).
Why it matters
Dual GIP and GLP-1 receptor agonism with tirzepatide achieves average weight loss exceeding 20% at higher doses, providing medical weight reduction of a magnitude previously seen predominantly with bariatric surgery.
Limits
The trial explicitly excluded individuals with type 2 diabetes, limiting generalizability to that population. The abstract does not report post-72-week durability, weight regain after discontinuation, or longer-term cardiovascular and safety outcomes.
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