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PubMed1 Apr 2026Diabetes, obesity & metabolism● 6/10i

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

le Roux CW, Busetto L, Aronne L, Horn DB, Dimitriadis GK et al.

About 23-34% of patients with obesity treated with tirzepatide and 14-21% treated with semaglutide reached proposed treat-to-target thresholds for waist-to-height ratio or BMI reduction. Post hoc analysis of SURMOUNT-5 trial, 751 patients, 72 weeks. This provides the first structured target framework for obesity treatment goals, moving beyond simple weight loss percentages to defined metabolic risk thresholds. The analysis was post hoc rather than a prespecified endpoint.

Strategic Signal

The treat-to-target framework provides Eli Lilly concrete efficacy benchmarks to communicate tirzepatide's superiority over Novo's semaglutide in payer discussions. US and EU health technology assessment bodies increasingly demand clear treatment goals and success metrics for obesity therapies. This data gives Lilly standardized endpoints to demonstrate value in ICER reviews and NICE appraisals, potentially strengthening formulary positioning against Wegovy.

GLP-1Weight lossDrug comparisonsEli LillyNovo Nordisk

Original Abstract

INTRODUCTION: With new advancements in obesity medicine, clarity on goals and expectations for successful disease management is limited. This post hoc analysis assessed application of proposed treat-to-target (TtT) thresholds for obesity to the outcome measures of SURMOUNT-5, which randomised participants with obesity to tirzepatide or semaglutide. METHODS: The proportion of participants in each treatment group reaching proposed TtT thresholds for waist to height ratio (WHtR) <0.53, body mass index (BMI) <27 kg/m2, or a combination was evaluated. The associations between the thresholds and achieving low disease activity to remission (meeting goals for at least four of five defined cardiometabolic risk parameters) and normalisation or improvement in SF-36v2 physical component score (PCS) from baseline to week 72 were explored. RESULTS: About 23.1%-33.9% of participants treated with tirzepatide and 14.2%-20.7% treated with semaglutide reached the TtT thresholds, with greater weight reduction than the overall population. About 77% of participants who reached WHtR <0.53 achieved low disease activity to remission, with an odds ratio of 2.31 (p < 0.001) compared to those who did not reach this target. The BMI threshold was not statistically associated with the assessed outcomes for SF-36v2 PCS. CONCLUSION: In this post hoc analysis of SURMOUNT-5, most participants who reached the proposed TtT thresholds achieved the goal of low disease activity to remission defined by cardiometabolic risk parameters. These data suggest that TtT thresholds in obesity medicine may clarify goals in shared decision-making and improve clinical outcomes.

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