Probiotics in Obese Patients Treated With GLP-1 Receptor Agonists

NCT07847593 | Completed

• 1 other identifier: CT/NB/160/2025/PR-MS
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 3

Brief Summary

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 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 and the proportion of 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 and duration, non-gastrointestinal adverse events, health-related quality of life, body weight reduction, treatment discontinuation, and inability to escalate the semaglutide dose as planned.weeks before semaglutide initiation and continuing throughout the 12-week semaglutide-treatment and dose-escalation period.

Conditions

Obesity (Disorder); GLP-1 Receptor Agonist Treatment; Probiotic Intervention; Diabetes Mellitus Type 2

Keywords

Obesity; GLP-1 receptor agonist treatment; Gatro-intestinal adverse events; Probiotics; Diabetes mellitus type 2

Outcome Measures

Primary Outcomes (2)

• Cumulative incidence proportion of gastrointestinal adverse events during semaglutide treatment

  .The cumulative incidence proportion of gastrointestinal adverse events (GI-AEs) was defined as the percentage of participants who experienced at least one protocol-defined GI-AE during the 12-week semaglutide treatment and dose-escalation period. GI-AEs included nausea, vomiting, diarrhea, constipation, abdominal pain, and flatulence and were assessed by investigators at monthly study visits. Cumulative incidence was calculated for any GI-AE and separately for each individual GI-AE as the number of participants experiencing the respective event at least once during the 12-week period divided by the number of participants assessed, multiplied by 100. A participant experiencing the same GI-AE at more than one visit was counted only once for that GI-AE. The possible range was 0%-100%, with higher values indicating a higher cumulative incidence.

  During the 12-week semaglutide treatment and dose-escalation period

• Prevalence of gastrointestinal adverse events during semaglutide treatment

  GI-AE prevalence was defined as the percentage of days during the 12-week semaglutide treatment period on which a participant reported at least one protocol-defined gastrointestinal adverse event (GI-AE) in the daily diary. Protocol-defined GI-AEs included nausea, vomiting, diarrhea, constipation, abdominal pain, and flatulence. A day on which more than one GI-AE was reported was counted only once for the overall GI-AE prevalence. For each participant, prevalence was calculated as the number of days with at least one GI-AE divided by the 84 planned semaglutide-treatment days, multiplied by 100. Group results were summarized as the mean participant-level GI-AE prevalence. The possible range was 0%-100%, with higher values indicating a greater proportion of treatment days affected by GI-AEs.

  During the 12-week semaglutide treatment and dose-escalation period

Secondary Outcomes (6)

• Change in Health-Related Quality of Life (SF-36v2)

  Baseline (before initiation of semaglutide treatment) and Week 12 (end of semaglutide treatment)

• Severity of Selected Gastrointestinal Adverse Events (GI-AEs)

  From initiation of semaglutide treatment through Week 12

• Number of Days With Individual Gastrointestinal Symptoms

  From initiation of semaglutide treatment through Week 12

• Change in Body Weight During Semaglutide Treatment

  Baseline (before initiation of semaglutide treatment) and during scheduled study visits through Week 12

• Number of Participants Who Discontinued Semaglutide Treatment

  From initiation of semaglutide treatment through Week 12

Study Arms (2)

Probiotic

EXPERIMENTAL

Participants assigned to this arm received the probiotic formulation in addition to semaglutide treatment.

Dietary Supplement: Four-strain probiotic formulation

Placebo

PLACEBO COMPARATOR

Participants assigned to this arm received a matching placebo containing maltodextrin in addition to semaglutide treatment.

Dietary Supplement: Maltodextrin (Placebo)

Interventions

Four-strain probiotic formulation DIETARY_SUPPLEMENT

The probiotic formulation contained Bifidobacterium animalis subsp. lactis AZHx1 (DSM 35201), Limosilactobacillus reuteri AZHx2 (DSM 35202), Lacticaseibacillus casei AZHx3 (DSM 35185), and Lacticaseibacillus rhamnosus AZHx4 (DSM 35757). It was administered orally in capsule form twice daily, at a total daily dose of 80 billion colony-forming units. Supplementation was initiated two weeks before the first dose of semaglutide and continued throughout the subsequent 12-week semaglutide-treatment and dose-escalation period, resulting in a total supplementation period of 14 weeks.

Probiotic

Maltodextrin (Placebo) DIETARY_SUPPLEMENT

The placebo contained maltodextrin and was matched to the probiotic formulation in appearance, packaging, and administration schedule. It was administered orally in capsule form twice daily for 14 weeks, beginning two weeks before the first dose of semaglutide and continuing throughout the subsequent 12-week semaglutide-treatment and dose-escalation period.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• BMI ≥ 30 kg/m² without T2DM or with coexisting T2DM;
• patients starting GLP-1RA treatment;
• provided written informed consent;
• patients with ability to adhere to the investigators' instructions regarding study protocol and procedures.

You may not qualify if:

• patients with gastrointestinal conditions unrelated to GLP-1RA therapy,
• 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.

Sponsors & Collaborators

• Nordic Biotic Sp. z o.o.: lead

Study Sites (3)

The Clinic Centrum Medyczne

Gdynia, 81-521, Poland

Location

Prywatna Specjalistyczna Praktyka Lekarska

Grudziądz, 86-300, Poland

Location

NEUROMEDIKA Indywidualna Specjalistyczna Praktyka Lekarska

Pruszcz Gdański, 83-000, Poland

Location

MeSH Terms

Conditions

Obesity; Diabetes Mellitus, Type 2

Interventions

maltodextrin

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Study Officials

• Dagmara Hering, Prof. MD, PhD

  Medical University of Gdansk, Department of Hypertension and Diabetology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2026
• First Posted: September 29, 2026
• Study Start: July 9, 2025
• Primary Completion: July 15, 2026
• Study Completion: July 15, 2026
• Last Updated: September 29, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

PL (3)