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

Gourgari, Evgenia; Srivastava, Gitanjali; Kelly, Aaron S; Mojdami, Donna; Cao, Dachuang; Murphy, Madhumita A; Karanikas, Chrisanthi A; Lee, Clare J · Obesity (Silver Spring) · 2025

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Abstract

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. 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. 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<sup>2</sup>) 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. 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. ClinicalTrials.gov identifiers: NCT04184622, NCT04657016, NCT04660643.

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