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Background <p>While randomized clinical trials (RCTs) establish the efficacy of anti-obesity medications (AOMs), their real-world effectiveness, inter-individual variability, and weight regain post discontinuation remain poorly characterized across diverse, large scale populations.</p> Methods <p>Electronic health records with pharmacy dispensation of obesity or overweight individuals were retrieved from local UT-Physician and nationwide EPIC COSMOS databases. AOMs were analyzed for short to long-term effectiveness on obesity relevant metrics.</p> Results <p>From the two cohorts, 71,318 (11·7%) and 1&#xa0;M (27·9%) individuals documented AOM exposures, respectively, with about 70% individuals experiencing more than one treatment session. Tirzepatide and Semaglutide outperformed other AOMs and were associated with up to 9·6[IQR:11]% and 6·2[IQR:11]% weight loss, respectively, and both improved blood pressure, HbA1c, and lipid profile. The median exposure durations were approximately 4·6 months for the two GLP-1/GIP AOMs, far short of the 72-week duration typically required for peak therapeutic benefit in RCTs. All AOMs showed substantial inter-individual variability in responses, regardless of exposure length. Substantial differences were found between RCT and real-world performance. For example, while Tirzepatide led both cohorts, nearly 50% and 25% of individuals didn’t achieve the 10% and 5% weight loss target respectively, after a minimum 72 weeks exposure, highlighting a notable effectiveness gap. Critically, we identified that Metformin co-therapy acted as a modifier of the ‘rebound effect,’ significantly attenuating (median 1·9 − 2·6%, <i>p</i> &lt; 0.0001) weight regain compared to semaglutide or tirzepatide monotherapy.</p> Conclusion <p>Our findings confirm real-world AOM effectiveness and reveal challenges of the ‘one-size-fits-all’ approach of current pharmacotherapy. The marked inter-individual variability suggests that stratified, personalized pharmacotherapy is essential to transform transient weight loss into sustainable metabolic health.</p> Clinical trial <p>Not applicable.</p>

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Current status of anti-obesity medications and performance, an EHR based survey

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月24日

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  • Xiaoyang Ruan,
  • Rui Li,
  • Liwei Wang,
  • Shuyu Lu,
  • Andrew Wen,
  • Murali Sameer,
  • Hongfang Liu

摘要

Background

While randomized clinical trials (RCTs) establish the efficacy of anti-obesity medications (AOMs), their real-world effectiveness, inter-individual variability, and weight regain post discontinuation remain poorly characterized across diverse, large scale populations.

Methods

Electronic health records with pharmacy dispensation of obesity or overweight individuals were retrieved from local UT-Physician and nationwide EPIC COSMOS databases. AOMs were analyzed for short to long-term effectiveness on obesity relevant metrics.

Results

From the two cohorts, 71,318 (11·7%) and 1 M (27·9%) individuals documented AOM exposures, respectively, with about 70% individuals experiencing more than one treatment session. Tirzepatide and Semaglutide outperformed other AOMs and were associated with up to 9·6[IQR:11]% and 6·2[IQR:11]% weight loss, respectively, and both improved blood pressure, HbA1c, and lipid profile. The median exposure durations were approximately 4·6 months for the two GLP-1/GIP AOMs, far short of the 72-week duration typically required for peak therapeutic benefit in RCTs. All AOMs showed substantial inter-individual variability in responses, regardless of exposure length. Substantial differences were found between RCT and real-world performance. For example, while Tirzepatide led both cohorts, nearly 50% and 25% of individuals didn’t achieve the 10% and 5% weight loss target respectively, after a minimum 72 weeks exposure, highlighting a notable effectiveness gap. Critically, we identified that Metformin co-therapy acted as a modifier of the ‘rebound effect,’ significantly attenuating (median 1·9 − 2·6%, p < 0.0001) weight regain compared to semaglutide or tirzepatide monotherapy.

Conclusion

Our findings confirm real-world AOM effectiveness and reveal challenges of the ‘one-size-fits-all’ approach of current pharmacotherapy. The marked inter-individual variability suggests that stratified, personalized pharmacotherapy is essential to transform transient weight loss into sustainable metabolic health.

Clinical trial

Not applicable.