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

Abstract

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.