Related Experiment Video
Updated: May 19, 2026
11:16
Progressive-ratio Responding for Palatable High-fat and High-sugar Food in Mice
Published on: May 3, 2012
Decoding the hallmarks of GLP-1RA weight-loss super-responders
A J Venkatakrishnan1,2, Karthik Murugadoss1,2, Venky Soundararajan1,2
1nference, Cambridge, MA 02142, United States.
Biology Methods & Protocols
|May 18, 2026
Summary
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) show varied weight loss results. Super responders achieving over 15% loss were more likely younger, female, and white, with specific conditions like fibromyalgia or psoriasis influencing outcomes.
Area of Science:
- Endocrinology
- Pharmacology
- Obesity Medicine
Background:
- Glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent a significant advancement in obesity treatment.
- However, real-world weight-loss outcomes demonstrate considerable variability among patients.
Purpose of the Study:
- To analyze weight-loss trajectories and identify factors associated with differential responses to GLP-1RAs (semaglutide and tirzepatide).
- To stratify patients into response categories: super responders (>15% weight loss), moderate responders (5%-15%), minimal responders (<5%), and weight regainers.
Main Methods:
- A federated biomedical platform analyzed data from 135,349 individuals treated with semaglutide and tirzepatide.
- Patients were categorized based on percentage of weight loss after treatment.
- Demographic and clinical characteristics of different response groups were compared.
Main Results:
- GLP-1RAs like Ozempic, Wegovy, Mounjaro, and Zepbound showed similar moderate response rates (40-42%).
- Super responder rates varied: Zepbound (34%), Wegovy (26%), Mounjaro (24%), and Ozempic (10%).
- Super responders were younger, more likely female, and white, with specific baseline conditions like fibromyalgia, osteoarthritis, or psoriasis correlating with response.
Conclusions:
- Significant heterogeneity exists in weight loss outcomes with GLP-1RA therapy.
- Factors such as age, sex, ethnicity, and pre-existing conditions influence weight-loss response.
- Further research is needed to develop personalized weight-management strategies.
Related Concept Videos
01:24Glucagon-like Receptor Agonists
Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
01:30Spare Receptors
Some receptors remain unoccupied even when an agonist produces a maximal response. Such empty ones are called spare receptors. In presence of spare receptors the maximum effect of an agonist drug is achieved with fewer than 100% of the receptors being occupied. To determine the presence of spare receptors, scientists often compare the concentration of the drug needed to produce 50% of the maximum effect (EC50) with the concentration of the drug needed to occupy 50% of the receptors (Kd). If the...