Setting Treatment Goals for Obesity: How Tirzepatide and Semaglutide Compare in Reaching Cardiometabolic Health Targets | Research

The takeaway

In the SURMOUNT-5 trial, 23-34% of tirzepatide patients versus 14-21% of semaglutide patients reached proposed treat-to-target thresholds, with 77% of those reaching a waist-to-height ratio below 0.53 achieving cardiometabolic disease remission.

77% achieved cardiometabolic remission at target
Among patients who reached a waist-to-height ratio below 0.53, 77% achieved low disease activity to remission across multiple cardiometabolic risk factors — validating this as a meaningful treatment target.

What the researchers found

In SURMOUNT-5 at 72 weeks, 23.1%-33.9% of tirzepatide-treated participants reached proposed treat-to-target (TtT) thresholds compared to 14.2%-20.7% with semaglutide. Those reaching targets had greater weight reduction than the overall population.

Among participants reaching a waist-to-height ratio (WHtR) <0.53, 77% achieved low disease activity to remission (meeting goals for at least 4 of 5 defined cardiometabolic risk parameters), with an odds ratio of 2.31 (p<0.001) compared to those not reaching this target. The BMI threshold was not statistically associated with quality of life outcomes (SF-36v2 physical component score).

Why it matters

Obesity medicine has lacked clear treatment targets — unlike diabetes (HbA1c goals) or hypertension (blood pressure targets). This analysis introduces a treat-to-target framework where specific body composition metrics predict cardiometabolic health outcomes. Finding that waist-to-height ratio is a better predictor than BMI alone could shift how obesity treatment success is measured, and the data show tirzepatide helps more patients reach these meaningful targets than semaglutide.

How the study worked

Post hoc analysis of the SURMOUNT-5 randomized trial comparing tirzepatide to semaglutide in participants with obesity over 72 weeks. Researchers evaluated the proportion reaching proposed TtT thresholds for waist-to-height ratio and BMI, then assessed associations between meeting these thresholds and achieving low disease activity to remission (defined by meeting ≥4 of 5 cardiometabolic risk parameters) and quality of life improvements (SF-36v2 physical component score).

What this study cannot tell us

This is a post hoc analysis, not a pre-specified trial endpoint, so results are hypothesis-generating. The TtT thresholds are proposed but not yet validated prospectively. The analysis cannot establish that reaching thresholds caused the cardiometabolic improvements (rather than being correlated). BMI-based targets were not associated with quality of life outcomes, limiting their utility. The trial population may not represent all patients with obesity.

How to read the evidence

This is a post hoc analysis of a large, head-to-head randomized controlled trial (SURMOUNT-5). The underlying trial data are strong, but the post hoc nature and proposed (not validated) treatment thresholds limit the evidence for the specific treat-to-target framework.

When this study was published

Published in 2026, this analysis applies emerging treat-to-target concepts to the latest SURMOUNT-5 trial data, representing the cutting edge of obesity treatment goal-setting.

The bigger picture

This analysis is part of a paradigm shift in obesity medicine from treating weight as a number to treating it as a disease with measurable health outcomes. The SURMOUNT-5 trial (the first head-to-head comparison of tirzepatide vs. semaglutide) already showed tirzepatide's superiority for weight loss. This post hoc analysis goes further by showing that weight loss translates to cardiometabolic disease remission when specific body composition targets are met — providing a framework for evidence-based goal setting in clinical practice.

Questions still open

Will prospective trials validate waist-to-height ratio as a treat-to-target metric for obesity treatment?
Should clinical guidelines incorporate body composition targets alongside or instead of BMI goals?
Could treat-to-target approaches improve insurance coverage and reimbursement for obesity medications?

Common questions

What is a treat-to-target approach for obesity?

Instead of just measuring how much weight someone loses, treat-to-target sets specific health goals — like a waist-to-height ratio below 0.53 or a BMI below a certain level. This analysis found that patients who reached these targets were much more likely to achieve actual improvements in heart and metabolic health, not just weight loss on a scale.

Is tirzepatide better than semaglutide for reaching health goals?

In this analysis, about a third of tirzepatide patients reached the proposed health targets compared to about a fifth on semaglutide. This aligns with the main SURMOUNT-5 findings showing tirzepatide produces greater weight loss. Importantly, patients who reached the targets on either drug had similar rates of cardiometabolic improvement.

Read the original research

A treat-to-target approach for obesity management: A post hoc analysis of the SURMOUNT-5 trial.

Diabetes, obesity & metabolism

View on PubMed ↗Publisher’s paper ↗

Citation

le Roux, Carel W; Busetto, Luca; Aronne, Louis; Horn, Deborah Bade; Dimitriadis, Georgios K; Falcon, Beverly; Garcia-Perez, Luis-Emilio; Valderas, Elisa Gomez; Gibble, Theresa Hunter; Senyucel, Cagri; Dunn, Julia P. (2026). A treat-to-target approach for obesity management: A post hoc analysis of the SURMOUNT-5 trial.. Diabetes, obesity & metabolism. https://doi.org/10.1111/dom.70531