Early-onset obesity tied to greater waist circumference, fasting insulin

Participants with early-onset obesity in the SURMOUNT clinical trials show a mixed profile of metabolic health at baseline despite a relatively young biological age. They exhibit concerning features, such as higher waist circumference and fasting insulin, as well as favourable features, including lower systolic blood pressure (SBP) and HbA1c compared with the late-onset group.

“Regardless of the age at obesity diagnosis, tirzepatide treatment was associated with similar benefits for all participants, with improvement in body weight (BW) and cardiometabolic risk factors,” the investigators said.

This post hoc analysis included 3,782 participants from SURMOUNT-1, -3, and -4 who were randomized to either tirzepatide or placebo. The investigators assessed the baseline characteristics and changes in BW and cardiometabolic risk factors at 72 and 88 weeks.

In SURMOUNT-1, participants with early-onset obesity exhibited longer mean obesity duration (20 vs 11 years), higher BMI (40 vs 37 kg/m²) and waist circumference (WC; 118 vs 112 cm), and lower HbA1c (5.48 percent vs 5.60 percent), triglycerides (median 120 vs 130 mg/dL), and SBP (121 vs 125 mm Hg) at baseline than those with late-onset obesity (p≤0.004 for all). [Obesity 2025;33:1668-1679]

At week 72, treatment with tirzepatide led to similar improvements in BW (‒23 percent vs ‒22 percent), waist circumference (‒22 vs ‒19 cm), HbA1c (‒0.51 percent vs ‒0.52 percent), triglycerides (‒32 percent vs ‒31 percent), and SBP (‒8 vs ‒8 mm Hg) between subgroups.

These findings persisted in both SURMOUNT-3 and -4 trials.

“Notably, the prevalence of prediabetes, hypertension, and dyslipidemia were relatively high (14 percent to 46 percent) in the early-onset group, thus underscoring the need for a better intervention in this group who otherwise may not receive medical attention based on their relatively young age,” the investigators said.

Visceral adiposity

Certain concerns were noted in this relatively young adult population with higher central adiposity and a higher degree of obesity since visceral adiposity had close associations with cardiovascular disease (CVD). Thus, mitigating the CVD risk at an earlier age could improve long-term outcomes. [Circulation 2015;132:1639-1647; Obesity Reviews 2021;22:e13088; Am J Prev Cardiol 2022;12:100430]

Additionally, the early-onset group had higher fasting insulin level, which indicated higher insulin resistance (IR). Other studies have likewise reported the presence of IR as a characteristic often seen in adolescents and young adults with obesity. This could suggest a unique pathophysiology of early-onset obesity. [Acta Endocrinologica (Buchar) 2018;14:330-337; Diabetes Care 2006;129:2427-2432]

“Combined with concurrent evidence of visceral adiposity, these findings suggest a potentially higher risk for incident type 2 diabetes and CVD in participants with early-onset obesity,” the investigators said. [JAMA Network Open 2024;7:e2434648; Circulation 2012;126:1301-1313; Diabetes Care 2020;43:1487-1495]

“Given the opportunity to prevent obesity-related complications in people with early-onset obesity, further studies are warranted to better understand early-onset obesity and potential solutions to improve their long-term health outcomes,” they added.