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Biosocial Variation in Treatment Response to GLP-1s: Implications for Clinical Care and Health Policy

Ralph I Horwitz1, Sydney Nur Otaka1, Allison Hayes Conroy2

  • 1Lewis Katz School of Medicine, Temple University, Philadelphia, Penn.

The American Journal of Medicine
|May 20, 2025
PubMed

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1s) show variable weight loss results. Personalized treatment considering patient biology and biography is crucial for managing obesity effectively.

Area of Science:

  • Pharmacology
  • Endocrinology
  • Public Health

Background:

  • Glucagon-like peptide-1 receptor agonists (GLP-1s) have shown significant promise in obesity treatment.
  • Widespread enthusiasm exists for GLP-1s among clinicians, patients, and policymakers due to reported average weight loss.
  • The average weight loss of 20-25% is often perceived as a universal outcome for obesity treatment.

Purpose of the Study:

  • To analyze the variability in weight loss outcomes associated with GLP-1s.
  • To investigate the pronounced variation observed in real-world evidence compared to clinical trials.
  • To explore the concept of biosocial pathogenesis as an explanation for treatment response heterogeneity.

Main Methods:

  • Review of randomized controlled trial data for GLP-1s.
  • Analysis of real-world evidence studies on GLP-1 treatment outcomes.
  • Examination of biosocial pathogenesis framework, integrating biological and biographical factors.

Main Results:

  • Significant variation in weight loss exists around the average treatment response for GLP-1s.
  • Weight loss variability is more pronounced in real-world data compared to randomized controlled trials.
  • Biosocial pathogenesis offers a potential framework to understand this observed variability.

Conclusions:

  • The effectiveness of GLP-1s in obesity management varies considerably among individuals.
  • A "one-size-fits-all" approach to GLP-1 therapy is insufficient.
  • Future research should focus on tailoring obesity treatments based on individual patient biology and biography.
Keywords:
BiosocialClinical trialsGLP-1sMethodologyVariation

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