NCT06825793

Semaglutide's Weight Loss Effects in Obesity

Clinical Assessment of Semaglutide-Induced Weight Reduction in Obese Populations

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 56 (estimated)
• Sponsor: Beijing Chao Yang Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

This is a non-randomized, concurrent, parallel-controlled clinical trial. The objective of this trial is to determine the relationship between weight loss responsiveness to semaglutide in obese patients and their gut microbiota.

Detailed description

Obesity has gradually emerged as a major public health concern. Although the GLP-1 receptor agonist semaglutide is used for chronic weight management in obese patients, significant individual variability exists in its weight-loss efficacy, and the underlying mechanisms remain unclear. Our preliminary studies have revealed that the low-response group to semaglutide exhibits significantly reduced plasma drug concentrations accompanied by a marked increase in the abundance of Prevotella copri (P. copri). Colonization with P. copri was found to attenuate semaglutide's weight-reducing effects in obese mice while decreasing its plasma concentration. In vitro experiments demonstrated an 85% degradation rate of semaglutide after 24-hour co-cultivation with P. copri. Based on these findings, we hypothesize that intestinal P. copri may produce specific enzymes that metabolize semaglutide, thereby influencing its therapeutic efficacy. This project aims to investigate the individual variability in semaglutide response through multi-omics approaches including fecal metagenomic sequencing. Utilizing in vitro bacterial screening platforms combined with gut microbiota gene knockout/heterologous expression systems, protein isolation-activity tracking, and structural characterization, we will elucidate the mechanisms underlying gut microbiota-mediated semaglutide resistance from microbial, animal, and clinical perspectives. The outcomes may identify novel therapeutic targets to overcome semaglutide resistance in weight management.

Conditions

• Obesity

Interventions

Type	Name	Description
DRUG	Semaglutide Subcutaneous Injection	All subjects received subcutaneous injections of semaglutide over a 28-week treatment period, which included an initial 16-week dose-escalation phase. The escalation protocol began with a starting dose of 0.25 mg administered once weekly. Every 4 weeks, the dose was gradually increased in a stepwise manner to 0.5 mg, 1.0 mg, 1.7 mg, and finally 2.4 mg, each administered once weekly.

Timeline

• Start date: 2025-02-20
• Primary completion: 2026-12-31
• Completion: 2027-12-31
• First posted: 2025-02-13
• Last updated: 2025-02-13