Probiotic Intervention for Digestive Health in Obese Patients Initiating GLP-RA Treatment

Obesity is a prevalent chronic disease affecting 17% of the French population. Treatment involves multiple factors, with pharmacotherapy playing an increasingly important role. GLP-1 receptor agonists (GLP1 RAs) are considered revolutionary in obesity treatment, with three approved molecules available in France: liraglutide, semaglutide, and tirzepatide. These treatments, combined with a healthy lifestyle, induce significant weight loss: 9% with liraglutide, 15% with semaglutide, and 20% with tirzepatide. The most common adverse events (AEs) associated with GLP-1 RAs are gastrointestinal (GI) disorders, including nausea, vomiting, diarrhea, and abdominal pain. These AEs are dose-dependent and often decline over time. In phase 3 trials, semaglutide 2.4 mg showed higher rates of GI AEs compared to placebo, but most were mild to moderate and transient. GI AEs led to dose reduction or temporary treatment interruption in 12.5% of participants, with few permanent discontinuations. Probiotics, are live microorganisms that benefit the host by improving gut microflora. Probiotics has been clinically proven to benefit gastrointestinal health. Probiotics may reduces symptoms of irritable bowel syndrome (IBS), improves gut barrier function, reduces inflammation, and decreases the incidence of C. difficile infection (CDI) in patients taking antibiotics. Probiotics is therefore theorized to potentially reduce GI side effects associated with GLP-1 RA treatment for obesity. Hypothesis Probiotics will prevent and limit the digestive disorders induced by GLP-1 R agonists, particularly during the dose escalation period. This would allow better digestive tolerance of the treatments, limiting the number of definitive treatment interruptions, facilitating compliance and dose escalation with a larger number of subjects at full dose and therefore with better systemic exposure to the compounds, a key factor in their effects on weight loss.

Obesity is a prevalent chronic disease affecting 17% of the French population. Treatment involves multiple factors, with pharmacotherapy playing an increasingly important role. GLP-1 receptor agonists (GLP1 RAs) are considered revolutionary in obesity treatment, with three approved molecules available in France: liraglutide, semaglutide, and tirzepatide. These treatments, combined with a healthy lifestyle, induce significant weight loss: 9% with liraglutide, 15% with semaglutide, and 20% with tirzepatide. The most common adverse events (AEs) associated with GLP-1 RAs are gastrointestinal (GI) disorders, including nausea, vomiting, diarrhea, and abdominal pain. These AEs are dose-dependent and often decline over time. In phase 3 trials, semaglutide 2.4 mg showed higher rates of GI AEs compared to placebo, but most were mild to moderate and transient. GI AEs led to dose reduction or temporary treatment interruption in 12.5% of participants, with few permanent discontinuations. Probiotics, are live microorganisms that benefit the host by improving gut microflora. Probiotics has been clinically proven to benefit gastrointestinal health. Probiotics may reduces symptoms of irritable bowel syndrome (IBS), improves gut barrier function, reduces inflammation, and decreases the incidence of C. difficile infection (CDI) in patients taking antibiotics. Probiotics is therefore theorized to potentially reduce GI side effects associated with GLP-1 RA treatment for obesity. Hypothesis Probiotics will prevent and limit the digestive disorders induced by GLP-1 R agonists, particularly during the dose escalation period. This would allow better digestive tolerance of the treatments, limiting the number of definitive treatment interruptions, facilitating compliance and dose escalation with a larger number of subjects at full dose and therefore with better systemic exposure to the compounds, a key factor in their effects on weight loss.