Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight

Aims: We assessed changes in body composition following tirzepatide treatment in a substudy of participants with obesity or overweight from the SURMOUNT-1 trial, overall and post hoc in clinically relevant subgroups. Materials and Methods: Substudy participants (n = 160 of the 2539 in SURMOUNT-1) underwent dual-energy X-ray absorptiometry (DXA) at baseline and Week 72. Body composition parameters were evaluated by analysis of covariance, logistic regression or Fisher's exact test. Post hoc subgroup analyses were conducted by sex (female or male), age (<50, 50 to <65, or >= 65 years) and total body weight reduction tertiles (<= 15.3 kg, >15.3 to <= 25.9 kg, or >25.9 kg). Results: The 160 participants (pooled tirzepatide doses n = 124, placebo n = 36) with baseline and end of study DXA data were 73% female and had a mean weight of 102.5 kg and body mass index of 38.0 kg/m(2). The change in body weight, fat mass and lean mass from baseline to Week 72 was -21.3%, -33.9% and -10.9% with tirzepatide and -5.3%, -8.2% and -2.6% with placebo, respectively (p < 0.001 for all comparisons). Of the body weight lost, approximately 75% was fat mass and 25% was lean mass for both tirzepatide and placebo. These proportions remained consistent across most subgroup analyses. Conclusions: In participants with obesity or overweight from the SURMOUNT-1 trial, tirzepatide treatment significantly reduced body weight, fat mass and lean mass compared with placebo, while in post hoc analyses, the proportion of body weight lost as fat or lean mass was relatively consistent including in clinically relevant subgroups.