December 4, 2022

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Terzepeptide once a week to treat obesity



Obesity is a chronic disease that leads to global morbidity and mortality. The efficacy and safety of terzepeptide, a glucose-dependent insulinotropic polypeptide and stimulator of the glucagon-like peptide-1 receptor, in obese individuals are not known.


In this phase 3 double-blind, randomized, controlled trial, we recruited 2,539 adults with a BMI (body mass index; weight in kilograms divided by the square of height in meters) of 30 or more, or 27 or more and at least one weight-related complication, excluding diabetes , in a 1:1:1 ratio to receive tirzepatide once a week, subcutaneously (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, including a 20-week dose increment period. Combined end points were the percentage change in weight from baseline and weight loss of 5% or more. Estimate the treatment regimen and evaluate the effects regardless of treatment discontinuation in the treatment intent community.


At baseline, the mean body weight was 104.8 kg, the mean BMI was 38.0, and the average BMI was 94.5% of participants were 30 or higher. The mean percent change in weight at week 72 was -15.0% (95% confidence interval [CI], −15.9 to −4.2) with weekly 5 mg doses of tirzepatide, −19.5% (95% CI, 20.4 to −18.5) at 10 mg doses, and 20.9% (95% CI, −21.8 to 19.9) at 15 mg doses and −3.1 % (95% CI, 4.3 to −1.9) with placebo (P < 0.001 for all comparisons with placebo). The percentage of participants who lost 5% or more of their weight was 85% (95% CI, 82 to 89), 89% (95% CI, 86 to 92), and 91% (95% CI, 88 to 94) with 5 mg, 10 mg, and 15 mg tirzepatide, respectively, and 35% (95% CI, 30 to 39) with placebo; 50% (95% CI, 46 to 54) and 57% (95% CI, 53 to 61) of participants in the 10 mg and 15 mg groups decreased body weight by 20% or more, compared with 3% (95% CI, 1 to 5) in the placebo group (p < 0.001 for all comparisons with placebo). Improvements in all cardiac measures predefined with tirzepatide were observed. The most common adverse events reported with tirzepatide were gastrointestinal, most were mild to moderate in severity, occurring primarily during dose escalation. Adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2%, and 2.6% of participants who received the 5 mg, 10 mg, and 15 mg terzepeptide doses and placebo, respectively.

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In this 72-week trial in obese participants, 5 mg, 10 mg, or 15 mg of tirzepatide once per week provided significant and sustained reductions in body weight. (Supported by Eli Lilly; SURMOUNT No.-1, NCT04184622.)