Vutiglabridin overcomes the GLP-1 RA-associated weight-loss plateau to achieve normal body weight
- 1Glaceum Inc., Suwon, Republic of Korea
Abstract
Background/Objectives: Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are highly effective for body weight reduction, there remains a critical unmet need for complementary strategies that drive selective fat loss and sustain long-term weight reduction. This study aimed to investigate whether Vutiglabridin, a novel oral small-molecule anti-obesity drug, complements GLP-1 RAs to enhance therapeutic efficacy by selectively reducing fat mass and achieving normal body composition.
Subjects/Methods: 6-week-old mice were fed a high-fat diet (60 kcal% fat) for 11 weeks to generate mice with diet-induced obesity (DIO) and then treated with GLP-1 RAs (Semaglutide, Liraglutide, or Exenatide) either alone or in combination with Vutiglabridin for 3–4 weeks.
Interventions/Methods: Body weight, food intake, fat mass, and lean mass were evaluated during treatment. For the drug discontinuation study, mice were administered Vutiglabridin, Semaglutide, or the combination for 4 weeks, after which treatment was withdrawn on Day 28 and body weight regain was monitored for 21 days.
Results: In DIO mice treated with Semaglutide, weight loss attenuated, and body weight was maintained at a constant level after 2 weeks. In contrast, co-administration of Vutiglabridin overcame this attenuation of efficacy, enabling continuous weight reduction and achieving normal body composition. Vutiglabridin also resolved the diminishing weight-loss effect when combined with comparatively less potent appetite-suppressing GLP-1 RAs, including liraglutide and exenatide. In addition to normalizing body composition, Vutiglabridin mitigated the body weight and fat-mass regain that occurs following Semaglutide discontinuation.
Conclusions: These findings demonstrate that Vutiglabridin can normalize body composition in combination with multiple GLP-1 RAs, highlighting its potential as a novel therapeutic option for obesity treatment.
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BibTeX
@article{lee2026vutiglabridin,
title = {{Vutiglabridin overcomes the GLP-1 RA-associated weight-loss plateau to achieve normal body weight}},
author = {Hyeong Min Lee and Kamindu Gayashan Marakkalage and Sang Hyo Kim and Soonje Lee and Jae Ho Lee and Hyung Soon Park and Sang-Ku Yoo},
journal = {International Journal of Obesity (2005)},
year = {2026},
month = jul,
doi = {10.1038/s41366-026-02161-9},
url = {https://doi.org/10.1038/s41366-026-02161-9},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Vutiglabridin overcomes the GLP-1 RA-associated weight-loss plateau to achieve normal body weight
AU - Hyeong Min Lee
AU - Kamindu Gayashan Marakkalage
AU - Sang Hyo Kim
AU - Soonje Lee
AU - Jae Ho Lee
AU - Hyung Soon Park
AU - Sang-Ku Yoo
PY - 2026
DA - 2026/07/15
JO - International Journal of Obesity (2005)
DO - 10.1038/s41366-026-02161-9
UR - https://doi.org/10.1038/s41366-026-02161-9
AB - Background/Objectives: Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are highly effective for body weight reduction, there remains a critical unmet need for complementary strategies that drive selective fat loss and sustain long-term weight reduction. This study aimed to investigate whether Vutiglabridin, a novel oral small-molecule anti-obesity drug, complements GLP-1 RAs to enhance therapeutic efficacy by selectively reducing fat mass and achieving normal body composition. Subjects/Methods: 6-week-old mice were fed a high-fat diet (60 kcal% fat) for 11 weeks to generate mice with diet-induced obesity (DIO) and then treated with GLP-1 RAs (Semaglutide, Liraglutide, or Exenatide) either alone or in combination with Vutiglabridin for 3–4 weeks. Interventions/Methods: Body weight, food intake, fat mass, and lean mass were evaluated during treatment. For the drug discontinuation study, mice were administered Vutiglabridin, Semaglutide, or the combination for 4 weeks, after which treatment was withdrawn on Day 28 and body weight regain was monitored for 21 days. Results: In DIO mice treated with Semaglutide, weight loss attenuated, and body weight was maintained at a constant level after 2 weeks. In contrast, co-administration of Vutiglabridin overcame this attenuation of efficacy, enabling continuous weight reduction and achieving normal body composition. Vutiglabridin also resolved the diminishing weight-loss effect when combined with comparatively less potent appetite-suppressing GLP-1 RAs, including liraglutide and exenatide. In addition to normalizing body composition, Vutiglabridin mitigated the body weight and fat-mass regain that occurs following Semaglutide discontinuation. Conclusions: These findings demonstrate that Vutiglabridin can normalize body composition in combination with multiple GLP-1 RAs, highlighting its potential as a novel therapeutic option for obesity treatment.
SN - 0307-0565
SN - 1476-5497
ER -