Probiotics in Obese Patients Treated With Semaglutide

This randomized, double-blind, placebo-controlled trial evaluated the effects of a four-strain probiotic formulation in adults with obesity receiving semaglutide. Participants received either the probiotic formulation or placebo, beginning two weeks before semaglutide initiation and continuing throughout the 12-week semaglutide-treatment and dose-escalation period. The primary objective was to determine whether probiotic supplementation reduced gastrointestinal adverse events associated with semaglutide treatment. The primary outcome comprised two complementary measures during the 12-week semaglutide-treatment period: the proportion of participants reporting at least one protocol-defined gastrointestinal adverse event during scheduled study visits and the proportion of evaluable treatment days on which a participant reported at least one protocol-defined gastrointestinal adverse event in the daily diary. Secondary outcomes included gastrointestinal symptom severity, the number of days with individual gastrointestinal adverse events, health-related quality of life, change in body weight, treatment discontinuation, and inability to escalate the semaglutide dose as planned. Additional gastrointestinal complaints and non-gastrointestinal symptoms were monitored as part of safety assessment.

Inclusion criteria: * Body Mass Index (BMI) of at least 30 kg/m², with or without coexisting type 2 diabetes mellitus; * patients initiating treatment with a glucagon-like peptide-1 receptor agonist; * provided written informed consent; * patients with ability to adhere to the investigators' instructions regarding study protocol and procedures. Exclusion criteria: * patients with gastrointestinal conditions unrelated to glucagon-like peptide-1 receptor agonist therapy, such as inflammatory bowel diseases, celiac disease, irritable bowel syndrome, gastroenteritis, gastric and duodenal ulcers, parasitic or bacterial intestinal infestation/infections, * known food allergies and lactose intolerance, * severe neurological conditions, malignancy, and hepatic or renal impairment, * pregnancy or breastfeeding, * anemia and leukocytosis in laboratory tests, * the use of intestine microbiota-targeted dietary supplements or drugs (i.e. probiotics, prebiotics, synbiotics, or postbiotics including butyric acid) within the last 3 months, * the use of antibiotics within the last 1 month, * the use of the following drugs: insulin, glucocorticosteroids, proton pump blockers, * a surgical procedure scheduled during the clinical study, * being enrolled in another clinical trial within the last 3 months, * alcohol or substance abuse.