Early Body-Composition Trajectory During Tirzepatide Treatment for Obesity: A Real-World Bioimpedance Cohort Study

Background/Objectives: Whether the loss of fat-free mass (FFM) during tirzepatide treatment exceeds the proportion expected in negative energy balance is debated, and the earliest weeks of treatment are the least characterized. We described the body-composition trajectory over the first 12 weeks of treatment in routine care. Methods: In this retrospective cohort of adults with obesity starting tirzepatide monotherapy, body weight, fat mass, FFM, total body water (TBW), and waist circumference were measured by single-frequency, foot-to-foot bioelectrical impedance analysis (BIA) at baseline and at approximately 4, 8, and 12 weeks, and were analyzed with linear mixed-effects models; follow-up values are available-data, on-treatment estimates. Results: Of 476 patients (mean age 40 years, 66% female, mean body-mass index 38.7 kg/m2), 268 had follow-up data and 111 were measured at 12 weeks. Estimated marginal body weight fell by 11.22 kg (10.4%), fat mass by 7.90 kg (16.8%), and BIA-derived FFM by 3.35 kg (5.4%) at 12 weeks (all p < 0.001); assuming 5-kg-less loss in patients without a 12-week measurement, the mean loss remained 7.4 kg. Of patients measured at 12 weeks, 89.2% had lost at least 5% and 57.7% at least 10% of body weight. In patients with complete data at baseline and 12 weeks (n = 85), fat mass accounted for 68.3% (95% CI 56.1 to 80.8) of the weight lost. Conclusions: Early weight loss during tirzepatide treatment was predominantly fat mass, with a BIA-derived FFM fraction numerically close to the commonly cited one-fourth. Because device-FFM equaled TBW divided by a fixed coefficient of 0.731 at every visit, it cannot separate water from lean tissue and is best read as an upper bound on lean tissue loss rather than a measure of muscle.