Tirzepatide Works Equally Well for People Who Developed Obesity Early in Life Versus Later | Research

The takeaway

A post hoc analysis of over 3,700 participants from the SURMOUNT trials found that tirzepatide produced similar weight loss (~22-23%) and cardiometabolic improvements regardless of whether obesity began before or after age 25.

23% weight loss in early-onset group
People who developed obesity before age 25 — despite having higher starting BMI and 20 years of obesity on average — achieved 23% body weight reduction with tirzepatide, matching the later-onset group.

What the researchers found

Across the SURMOUNT-1, SURMOUNT-3, and SURMOUNT-4 trials (N=3,782), participants with early-onset obesity (diagnosed before age 25) had distinct baseline profiles compared to later-onset obesity: higher BMI (40 vs. 37 kg/m²), larger waist circumference (118 vs. 112 cm), longer obesity duration (20 vs. 11 years), but paradoxically lower HbA1c (5.48% vs. 5.60%), triglycerides (120 vs. 130 mg/dL), and systolic blood pressure (121 vs. 125 mmHg).

Despite these baseline differences, tirzepatide treatment produced remarkably similar outcomes in both groups at 72 weeks: body weight reduction (-23% vs. -22%), waist circumference reduction (-22 vs. -19 cm), HbA1c improvement (-0.51% vs. -0.52%), triglyceride reduction (-32% vs. -31%), and systolic blood pressure reduction (-8 vs. -8 mmHg). These consistent results were replicated across all three SURMOUNT trials.

Why it matters

Early-onset obesity has been linked to more severe metabolic complications and is sometimes perceived as harder to treat. This analysis provides reassurance that tirzepatide is equally effective for people who have lived with obesity since childhood or young adulthood, even though they tend to start with higher BMI and have had obesity for much longer.

How the study worked

This was a post hoc analysis pooling data from three randomized, placebo-controlled SURMOUNT clinical trials. Participants (N=3,782) were divided into early-onset obesity (diagnosed before age 25) and later-onset obesity subgroups. Researchers compared baseline characteristics and changes in body weight and cardiometabolic risk factors at 72 or 88 weeks of tirzepatide versus placebo treatment.

What this study cannot tell us

This was a post hoc analysis, not a pre-specified comparison, so results should be interpreted with caution. Age of obesity onset was self-reported and may be inaccurate. The trials may not have been powered to detect differences between subgroups. The study population may not fully represent the diversity of people with early-onset obesity, particularly those with genetic or syndromic causes.

How to read the evidence

This is a post hoc analysis of three large, well-designed randomized controlled trials (SURMOUNT-1, -3, -4). While the primary trials represent high-quality evidence, this subgroup analysis was not pre-specified, which lowers the evidence grade somewhat.

When this study was published

Published in 2025, this is a very recent analysis of the landmark SURMOUNT trial data, reflecting the latest evidence on tirzepatide's effectiveness across different patient populations.

The bigger picture

Tirzepatide, a dual GIP/GLP-1 receptor agonist peptide, has emerged as one of the most effective anti-obesity treatments available. This analysis addresses an important clinical question: whether the drug works as well for people with longstanding, early-onset obesity — a population that may have different underlying biology and has historically been underserved by weight management therapies. The consistent results across subgroups strengthen the case for broad clinical use.

Questions still open

Does early-onset obesity involve different biological mechanisms that could affect long-term response to GLP-1/GIP peptide therapies beyond the study period?
Would tirzepatide be equally effective in people with genetic or syndromic forms of early-onset obesity who were likely excluded from SURMOUNT trials?
Why do people with early-onset obesity show a paradoxically healthier metabolic profile (lower HbA1c, blood pressure) despite higher BMI?

Common questions

What is tirzepatide and how does it work?

Tirzepatide is a synthetic peptide that activates both GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptors. This dual action helps regulate appetite, blood sugar, and metabolism, leading to significant weight loss and improvements in cardiometabolic health markers.

Does it matter when someone first became obese for tirzepatide to work?

According to this analysis, no. People who developed obesity before age 25 achieved virtually the same weight loss (~23%) and metabolic improvements as those who developed obesity later in life, despite having lived with obesity for nearly twice as long on average.

Read the original research

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

Obesity (Silver Spring, Md.), 33(9), 1668-1679

View on PubMed ↗Publisher’s paper ↗

Citation

Gourgari, Evgenia; Srivastava, Gitanjali; Kelly, Aaron S; Mojdami, Donna; Cao, Dachuang; Murphy, Madhumita A; Karanikas, Chrisanthi A; Lee, Clare J. (2025). Early-Onset Obesity and Tirzepatide Treatment: A Post Hoc Analysis of the SURMOUNT Clinical Trials.. Obesity (Silver Spring, Md.), 33(9), 1668-1679. https://doi.org/10.1002/oby.24348