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Purpose <p>The SURMOUNT-5 trial demonstrated greater weight reduction with tirzepatide vs. semaglutide in adults with obesity without diabetes. This study compared real-world weight reduction and cardiometabolic parameters associated with tirzepatide and semaglutide for obesity management.</p> Methods <p>A retrospective cohort study was conducted using Truveta de-identified US electronic health record data. Adults with obesity or overweight and ≥ 1 obesity-related complication, without diabetes, who initiated tirzepatide or semaglutide December 2023–June 2024 and adhered to treatment, were followed for 6 months. Primary outcome was percentage weight change from baseline. Secondary outcomes included weight-reduction targets and changes in body mass index (BMI) and cardiometabolic parameters. Primary analysis employed propensity-score weighted regression. Sensitivity analyses included modified intention-to-treat.</p> Results <p>Among 2,396 on-treatment patients (1,003 tirzepatide; 1,393 semaglutide), greater 6-month mean percentage weight reduction was observed with tirzepatide (–11.15% vs. −8.83%; adjusted difference −2.32%-points [95% CI: −3.17, −1.48]). Higher proportions of tirzepatide-treated patients achieved 5%, 10%, 15%, and 20% weight-reduction targets. Greater reductions in BMI, blood pressure, and haemoglobin A1c were observed with tirzepatide. More patients received higher doses of semaglutide (≥ 1.7&#xa0;mg; 67.7%) vs. tirzepatide (≥ 10&#xa0;mg; 42.4%). Sensitivity analysis findings were consistent.</p> Conclusions <p>Consistent with clinical trials, real-world tirzepatide treatment was associated with greater 6-month weight reduction and more frequent achievement of weight-reduction targets and improvements in select cardiometabolic parameters than semaglutide among adults with obesity without diabetes. This early emergence of tirzepatide’s comparative advantage over semaglutide was observed despite more semaglutide-treated patients receiving higher doses than tirzepatide-treated patients.</p>

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Comparative effectiveness of tirzepatide and semaglutide for obesity management in US clinical practice: a 6-month retrospective cohort study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月9日

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  • Carel W. le Roux,
  • Nicolae Done,
  • Alan J. M. Brnabic,
  • Abigail Zion,
  • Ilya Lipkovich,
  • Zbigniew Kadziola,
  • Julia P. Dunn,
  • Urvi Desai,
  • Noam Kirson,
  • Georgios K. Dimitriadis,
  • Hong Kan

摘要

Purpose

The SURMOUNT-5 trial demonstrated greater weight reduction with tirzepatide vs. semaglutide in adults with obesity without diabetes. This study compared real-world weight reduction and cardiometabolic parameters associated with tirzepatide and semaglutide for obesity management.

Methods

A retrospective cohort study was conducted using Truveta de-identified US electronic health record data. Adults with obesity or overweight and ≥ 1 obesity-related complication, without diabetes, who initiated tirzepatide or semaglutide December 2023–June 2024 and adhered to treatment, were followed for 6 months. Primary outcome was percentage weight change from baseline. Secondary outcomes included weight-reduction targets and changes in body mass index (BMI) and cardiometabolic parameters. Primary analysis employed propensity-score weighted regression. Sensitivity analyses included modified intention-to-treat.

Results

Among 2,396 on-treatment patients (1,003 tirzepatide; 1,393 semaglutide), greater 6-month mean percentage weight reduction was observed with tirzepatide (–11.15% vs. −8.83%; adjusted difference −2.32%-points [95% CI: −3.17, −1.48]). Higher proportions of tirzepatide-treated patients achieved 5%, 10%, 15%, and 20% weight-reduction targets. Greater reductions in BMI, blood pressure, and haemoglobin A1c were observed with tirzepatide. More patients received higher doses of semaglutide (≥ 1.7 mg; 67.7%) vs. tirzepatide (≥ 10 mg; 42.4%). Sensitivity analysis findings were consistent.

Conclusions

Consistent with clinical trials, real-world tirzepatide treatment was associated with greater 6-month weight reduction and more frequent achievement of weight-reduction targets and improvements in select cardiometabolic parameters than semaglutide among adults with obesity without diabetes. This early emergence of tirzepatide’s comparative advantage over semaglutide was observed despite more semaglutide-treated patients receiving higher doses than tirzepatide-treated patients.