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Real-World GLP-1 Therapy Yields Lower Weight Loss, Spurs Tetra-Receptor Drug Research

New Cleveland Clinic data show that treatment discontinuation and low maintenance doses limit semaglutide’s and tirzepatide’s real-world weight-loss benefits, prompting exploration of four-receptor agonists.

Wegovy pens are sorted at a packaging line at Novo Nordisk's facility in Hillerod, Denmark, March 8, 2024. REUTERS/Tom Little/File Photo
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Overview

  • Over 20% of patients stopped GLP-1 treatment within three months and 32% discontinued between three and twelve months, undermining weight-loss outcomes.
  • Patients who remained on therapy lost 11.9% of body weight after one year, compared with 3.6% among early discontinuers and 6.8% among those who stopped later.
  • High maintenance doses increased efficacy, with semaglutide users losing up to 13.7% of body weight and tirzepatide users up to 18%, and tirzepatide delivering stronger results at equivalent doses.
  • Continued GLP-1 therapy normalized blood sugar in 67.9% of prediabetic patients, significantly higher than the 33% rate observed among those who discontinued early.
  • Tufts University researchers have engineered a unimolecular tetra-receptor agonist targeting GLP-1, GIP, glucagon and PYY to potentially improve adherence and amplify weight-loss effects in clinical use.