Early-Onset Obesity and Tirzepatide Treatment: A Post Hoc Analysis of the SURMOUNT Clinical Trials.

OBJECTIVE: People with early-onset obesity (diagnosed at age < 25 years) may present with more cardiometabolic abnormalities and obesity-related complications. This post hoc analysis assessed baseline characteristics and body weight (BW) changes with tirzepatide in people with early- versus later-onset obesity. METHODS: Participants (N = 3782) from SURMOUNT-1, SURMOUNT-3, and SURMOUNT-4 randomized to tirzepatide or placebo were included. Baseline characteristics and changes in BW and cardiometabolic risk factors at 72/88 weeks were assessed. RESULTS: In SURMOUNT-1, participants with early- versus later-onset obesity had longer mean obesity duration (20 ± 12 vs. 11 ± 8 years), higher BMI (40 ± 7 vs. 37 ± 6 kg/m) and waist circumference (WC, 118 ± 16 vs. 112 ± 14 cm), and lower HbA1c (5.48% ± 0.4% vs. 5.60% ± 0.4%), triglycerides (median 120 vs. 130 mg/dL), and systolic blood pressure (SBP; 121 ± 13 vs. 125 ± 13 mmHg) at baseline (all p ≤ 0.004). At 72 weeks, improvements with tirzepatide in BW (-23% vs. -22%), WC (-22 vs. -19 cm), HbA1c (-0.51% vs. -0.52%), triglycerides (-32% vs. -31%), and SBP (-8 vs. -8 mmHg) were similar between subgroups. Similar improvements were observed in SURMOUNT-3 and SURMOUNT-4. CONCLUSIONS: In this post hoc analysis, participants with early- versus later-onset obesity exhibited a mixed profile of metabolic health at baseline, including a higher degree of central adiposity and lower HbA1c and SBP. Improvements in BW and cardiometabolic markers with tirzepatide were similar between subgroups. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT04184622, NCT04657016, NCT04660643.