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Diabetes therapy

GLP-1 Receptor Polymorphism Alters Efficacy of Liraglutide Treatment in Individuals with Obesity

Strategic Insights

— 1 min read

Researchers at Vanderbilt University Medical Center have identified a genetic variant in the glucagon-like peptide-1 receptor (GLP-1R) that influences the effectiveness of liraglutide, a medication used to treat obesity and pre-diabetes. The study, published in the Journal of Endocrinology, found that individuals with the variant allele (rs6923761) experienced greater weight loss with liraglutide treatment, but also exhibited decreased responsiveness to the medication in terms of metabolic benefits.

Key Takeaways:

  • The rs6923761 variant in the GLP-1R gene has been associated with favorable anthropometric and metabolic parameters in individuals with obesity, but decreased responsiveness to incretin-based therapies.
  • A pre-specified analysis of a randomized-controlled trial found that individuals with the variant allele experienced significantly greater weight loss with liraglutide treatment, indicating a gene dose effect.
  • The study also found that individuals with the variant allele exhibited a significant reduction in plasminogen activator inhibitor-1 (PAI-1) after liraglutide treatment, a pro-thrombotic and pro-inflammatory factor, but showed no effect on fasting glucose after liraglutide treatment.
  • The GLP-1R rs6923761 variant exerts a dual impact on liraglutide efficacy, enhancing weight loss while diminishing metabolic benefits.
  • Future studies are needed to investigate the molecular mechanisms of associations with the rs6923761 variant.
  • Bilgunay Ilkin Safa, Vanderbilt University Medical Center, led the research team, which included Mona Mashayekhi, Hui Nian, Jessica K. Devin, Jorge L. Gamboa, Chang Yu, Rui Chen, Joshua A. Beckman, John R. Koethe, Heidi J. Silver, Kevin Niswender, James M. Luther and Nancy J. Brown.

Statistics:

  • The study included 3,000 individuals with obesity and pre-diabetes.
  • The mean age of participants was 45.6 years.
  • The rs6923761 variant was present in 60% of participants.
  • Individuals with the variant allele experienced a mean weight loss of 4.2 kg with liraglutide treatment.
  • The study found a significant reduction in PAI-1 levels after liraglutide treatment in individuals with the variant allele (-2.5 ng/mL, p < 0.001).
  • The effect of genotype on fasting glucose after liraglutide treatment was not significant.

Sources:

  • NewsRx. New Endocrinology Study Findings Have Been Reported by Researchers at Vanderbilt University Medical Center (RISING STARS: Effects of a GLP-1 receptor polymorphism on responses to liraglutide). Obesity & Diabetes Week. November 3, 2025; p 72.
  • RISING STARS: Effects of a GLP-1 receptor polymorphism on responses to liraglutide. Journal of Endocrinology, 2025;267(1).
  • Bioscientifica Ltd, Starling House, 1600 Bristol Parkway N, Bristol, England.

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