Obesity is a long-term condition that results in significant international morbidity and mortality. The efficacy and safety of tirzepatide, a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, in individuals with being overweight are not acknowledged.


In this section 3 double-blind, randomized, controlled trial, we assigned 2539 grownups with a overall body-mass index (BMI the weight in kilograms divided by the sq. of the height in meters) of 30 or extra, or 27 or a lot more and at least one particular excess weight-associated complication, excluding diabetes, in a 1:1:1:1 ratio to get when-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 months, like a 20-7 days dose-escalation time period. Coprimary conclusion factors ended up the proportion improve in body weight from baseline and a bodyweight reduction of 5% or much more. The cure-routine estimand assessed outcomes no matter of remedy discontinuation in the intention-to-take care of population.


At baseline, the necessarily mean overall body body weight was 104.8 kg, the imply BMI was 38., and 94.5% of individuals had a BMI of 30 or higher. The mean percentage alter in bodyweight at week 72 was −15.% (95% self-assurance interval [CI], −15.9 to −14.2) with 5-mg weekly doses of tirzepatide, −19.5% (95% CI, −20.4 to −18.5) with 10-mg doses, and −20.9% (95% CI, −21.8 to −19.9) with 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 had weight reduction of 5% or more 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 of 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 had a reduction in body weight of 20% or more, as compared with 3% (95% CI, 1 to 5) in the placebo group (P<0.001 for all comparisons with placebo). Improvements in all prespecified cardiometabolic measures were observed with tirzepatide. 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%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses and placebo, respectively.


In this 72-week trial in participants with obesity, 5 mg, 10 mg, or 15 mg of tirzepatide once weekly provided substantial and sustained reductions in body weight. (Supported by Eli Lilly SURMOUNT-1 number, NCT04184622.)