Efficacy and safety of once-weekly tirzepatide in Japanese patients with obesity disease (SURMOUNT-J): a multicentre, randomised, double-blind, placebo-controlled phase 3 trial.

BACKGROUND: Data on tirzepatide in Asian patients with obesity are limited. This study aimed to gain a better understanding of tirzepatide for treatment of Japanese patients with obesity disease (BMI ≥25 kg/m with excessive fat accumulation) as defined by the Japanese Society for the Study of Obesity. METHODS: This was a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial of the efficacy and safety of tirzepatide as an adjunct to lifestyle modifications. Japanese adults with obesity disease (BMI ≥27 kg/m accompanied by ≥2 obesity-related health disorders or ≥35 kg/m accompanied by ≥1 obesity-related health disorders), excluding diabetes, were assigned 1:1:1 via computer-generated random sequence to receive once weekly subcutaneous tirzepatide (10 mg or 15 mg) or placebo. Coprimary endpoints were the mean percent change in bodyweight and the proportion of participants achieving at least 5% bodyweight reduction at week 72, using the efficacy estimand. Efficacy and safety were assessed in the modified intention-to-treat (mITT) population. This study is registered with ClinicalTrials.gov, NCT04844918. FINDINGS: Between May 10, 2021, and June 24, 2023, 413 participants were screened, and 267 were randomly assigned. Due to exclusion of one study site, the mITT population was 225 participants (133 [59%] men and 92 [41%] women, mean age 50·8 [SD 10·7] years), with 73 in the tirzepatide 10 mg group, 77 in the tirzepatide 15 mg group, and 75 in the placebo group, of whom 192 (85%) completed both study and treatment. Estimated treatment differences relative to placebo in change in bodyweight at week 72 were -16·1% (95% CI -18·7 to -13·5; p<0·0001) and -21·1% (95% CI -23·6 to -18·5; p<0·0001) following tirzepatide 10 mg and 15 mg, respectively. At week 72, a higher proportion of participants achieved at least 5% bodyweight reduction with tirzepatide 10 mg (67 [94%] of 71) and 15 mg (73 [96%] of 76) compared with placebo (15 [20%] of 75; both p<0·0001). Cardiometabolic and body composition indices were also improved with tirzepatide. Participants treated with tirzepatide experienced treatment-emergent adverse events more frequently (10 mg: n=61 [84%]; 15 mg: n=66 [86%]) than those who received placebo (52 [69%]), most commonly gastrointestinal symptoms. Study discontinuations due to adverse events were infrequent (placebo: n=3 [4%]; tirzepatide 10 mg: n=1 [1%]; tirzepatide 15 mg: n=0). INTERPRETATION: In Japanese adults with obesity disease, tirzepatide provided clinically a meaningful reduction in bodyweight compared with placebo over 72 weeks, with a safety profile consistent with that observed in global populations. FUNDING: Eli Lilly and Company. TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.