Obesity &Amp; OverweightPROBIO-GLP1NCT07213323
Probiotic Intervention for Digestive Health in Obese Patients Initiating GLP-RA Treatment
A study testing Probiotics (Natural product) in people with Obesity &Amp; Overweight and Digestive Disorders, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Obesity &Amp; Overweight, Digestive Disorders
- What is being tested?
- Probiotics (Natural product)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteFrance
- Study dates
- 5 Aug 2026to 5 Aug 2028
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient who is going to start a GLP-1 RA (semaglutide or tirzepatide) for weight management
- Men or Women
- BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 associated with one or more co-morbidities (arterial hypertension, sleep apnea, dyslipidemia, arthritis)
- Between 18 and 75 years old
- In the opinion of the investigator, the patient must have adequate support to comply with the entire study requirements as described in the protocol (e.g. transportation to and from trial site, ability to understand and fill the self-rating scales, drug compliance, availability to attend to the scheduled visits, etc…).
- Patient who agrees to be included in the study and who signs the informed consent form
- Female participants of childbearing potential must agree to use effective contraception
- Patient affiliated to a healthcare insurance plan
Who cannot join
- Criteria relating to the study population:
- Patients under 18 years old
- Patient with contraindication to semaglutide or tirzepatide according to the Summary of Product Characteristics (SPC).
- Patients scheduled for bariatric surgery during the study period
- Patients who have had bariatric surgery in the last 12 months
- Patient with a current diagnosis of diabetes.
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- Patients with a current diagnosis of liver cirrhosis, short bowel syndrome or inflammatory bowel disease (IBD).
- Patients with severely weakened immune system.
- Clinically unstable medical disease, including cardiovascular, hepatic, renal, gastrointestinal, pulmonary, metabolic, endocrine, or other systemic disease.
- Product criteria:
- Patient with known allergy to the product of the study
- Prohibited treatments :
- Current associated treatments or used in the last 30 days: GLP-1 RA, Anti-obesity drugs (AOD), Corticosteroids, Atypical neuroleptics, Antibiotics, Probiotics, Prebiotics
- Regulatory criteria :
- Persons deprived of their liberty by a judicial or administrative decision
- Persons under psychiatric care
- Persons admitted to a health or social institution for purposes other than research
- Adults subject to a legal protection measure (guardianship, curatorship)
- Persons not affiliated to a social security scheme or beneficiaries of a similar scheme
- Subjects participating in other interventional research with an exclusion period still in progress at pre-inclusion
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Hôpital Lyon Sud
Pierre-Bénite, 69495
Emmanuel DISSE, MD PhD, +33478861484, Emmanuel.disse@chu-lyon.fr
About this study
Official title: Evaluation of the Efficacy of Probiotics on Digestive Quality of Life in Patients Initiating GLP-1 Receptor Agonists for the Treatment of Obesity. A Randomized, Double-blind Trial
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.
Read more
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.
Read the detailed description
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.
- Conditions
- Obesity &Amp; Overweight, Digestive Disorders
- Being tested
- Probiotics (Natural product), Placebo
- Keywords
- GLP1 R-agonist, Probiotics, Quality of life
- Medical subject headings
- Obesity, Overweight, Digestive System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Probiotics (Natural product)Dietary supplement
Participants will be instructed to daily take, during 26 weeks (that will begin 2 weeks before the initiation of semaglutide or tirzepatide treatment) one capsule of a probiotic with water at room temperature with the first meal.
Dosage levels: 1 capsule Digestive Quality of life during the study will be assessed.
PlaceboOther
Participants will be instructed to daily take, during 26 weeks (that will begin 2 weeks before the initiation of semaglutide or tirzepatide treatment) one capsule of PLACEBO with water at room temperature with the first meal.
Digestive Quality of life during the study will be assessed.
| Study group | Role | What they receive |
|---|---|---|
| Probiotics | Experimental | Obese subjects who are going to start a GLP-1 R-agonist (semaglutide or tirzepatide) as part of their weight management in routine clinical practice will received during 26 weeks 1 capsule a day every morning of probiotics that will begin 2 weeks before the initiation of semaglutide or tirzepatide treatment. Receives: Dietary Supplement: Probiotics (Natural product) |
| Placebo | Placebo comparator | Obese subjects who are going to start a GLP-1 R-agonist (semaglutide or tirzepatide) as part of their weight management in routine clinical practice will received during 26 weeks 1 capsule a day every morning of PLACEBO that will begin 2 weeks before the initiation of semaglutide or tirzepatide treatment. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of the Limitation of the impairment in digestive quality of life during the dose escalation of GLP1-RA (semaglutide or tirzepatide)
Assessment using partial GIQLI Score (5 items: 1,27,31,32,33 of the total GIQLI) in each GLP-1 RA group measured 4 weeks following the previous dose escalation, with the GLP1-RA dose standardized on a 0-1 scale.
Item 1 for abdominal pain, Item 27 for dyspepsia, Item 31 for diarrhea, item 32 for constipation and Item 33 for nausea.
For each item, 5 responses will be proposed to the patients and for each answer, a score ranging from 0 to 4 will be assigned The highest score is 20 and defines a more favorable health state
Measured: Every 5 weeks
Secondary outcomes (20)
Digestive quality of life
Comparison between the probiotic group and placebo group in the whole population and in the subpopulation of subjects having reached the planned GLP-1 RA treatment dose at 24 weeks, according to the dose escalation design:
Evolution of the partial GIQLI Scores (Questions 1,27,31,32,33). Item 1 for abdominal pain, Item 27 for dyspepsia, Item 31 for diarrhea, item 32 for constipation and Item 33 for nausea.
For each item, 5 responses and for each answer, a score ranging from 0 to 4. The highest score is 20 and defines a more favorable health state
Measured: From baseline to 4, 8, 12, 16, 20 and 24 weeks of treatment
Nausea
Comparison of nausea between the probiotic group and placebo group in the whole population and in the subpopulation of subjects having reached the planned GLP-1 RA treatment dose at 24 weeks, according to the dose escalation design:
Evolution of partial GIQLI score (question 33) of nausea score ranging from 0 to 4.
4 defines the more favourable score
Measured: From baseline to 4, 8, 12, 16, 20 and 24 weeks of treatment
Dyspepsia
Comparison of dyspepsia between the probiotic group and placebo group in the whole population and in the subpopulation of subjects having reached the planned GLP-1 RA treatment dose at 24 weeks, according to the dose escalation design:
Evolution of partial GIQLI score (question 27) of dyspepsia score ranging from 0 to 4.
4 defines the more favourable score
Measured: From baseline to 4, 8, 12, 16, 20 and 24 weeks of treatment
Diarrhea
Comparison of diarrhea between the probiotics group and placebo group in the whole population and in the subpopulation of subjects having reached the planned GLP-1 RA treatment dose at 24 weeks, according to the dose escalation design:
Evolution of partial GIQLI score (question 31) of diarrhea score ranging from 0 to 4.
4 defines the more favourable score
Measured: From baseline to 4, 8, 12, 16, 20 and 24 weeks of treatment
Constipation
Comparison of constipation between the probiotic group and placebo group in the whole population and in the subpopulation of subjects having reached the planned GLP-1 RA treatment dose at 24 weeks, according to the dose escalation design:
Evolution of partial GIQLI score (question 32) of constipation score ranging from 0 to 4.
4 defines the more favourable score
Measured: From baseline to 4, 8, 12, 16, 20 and 24 weeks of treatment
Abdominal pain
Comparison of abdominal pain between the probiotic group and placebo group in the whole population and in the subpopulation of subjects having reached the planned GLP-1 RA treatment dose at 24 weeks, according to the dose escalation design:
Evolution of partial GIQLI score (question 1) of abdominal pain score ranging from 0 to 4.
4 defines the more favourable score
Measured: From baseline to 4, 8, 12, 16, 20 and 24 weeks of treatment
GLP-1 receptor agonist dosage
Average GLP-1 RA dose
Measured: 4, 8, 12, 16, 20 and 24 weeks of intervention
GLP1-RA dose escalation
Proportion of patients having reached the planned GLP-1 RA treatment dose according to the dose escalation protocol at 4, 8, 12, 16, 20 and 24 weeks
Measured: 4, 8, 12, 16, 20 and 24 weeks of intervention
GLP1-RA dose discontinuation/maintenance
Proportion of patients who had to reduce or to interrupt definitively their GLP-1 RA treatment dose at 4, 8, 12, 16, 20 and 24 weeks
Measured: 4, 8, 12, 16, 20 and 24 weeks of intervention
Weight loss
Percent of weight change from baseline
Measured: 4, 8, 12, 16, 20 and 24 weeks of intervention
Weight loss
absolute change in body weight from baseline
Measured: 4, 8, 12, 16, 20 and 24 weeks of intervention
Weight loss
Rate of patients achieving a body weight reduction of ≥5%, ≥10%, ≥15%
Measured: 4, 8, 12, 16, 20 and 24 weeks of intervention
Quality of life assessed with GIQLI questionnaire
This questionnaire consists of 36 items exploring 5 dimensions or subscales: symptoms, physical condition, emotions, social integration and the effect of any medical treatment. For each item, 5 responses will be proposed to the patients and for each answer, a score ranging from 0 to 4 (highest score = 144) will be assigned. A high score defines a more favorable health state.
Measured: baseline, 12 and 24 weeks of treatment
Quality of life assessed with SF36 questionnaire
This questionnaire taps eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/tiredness, and general health perceptions. It also includes a single item that provides an indication of a perceived change in health
Measured: baseline, 12 and 24 weeks of treatment
Fat mass
Measurement of fat mass will explore the body composition. Results will be expressed in kg and %
Measured: Baseline, before implementation of GLP1-RA, 12 and 24 weeks of treatment
Lean mass
Measurement of lean mass will explore the body composition. Results will be expressed in kg and %
Measured: Baseline, before implementation of GLP1-RA, 12 and 24 weeks of treatment
Skeletal muscle mass
Measurement of skeletal muscle mass will explore the body composition. Results will be expressed in kg and %
Measured: Baseline, before implementation of GLP1-RA, 12 and 24 weeks of treatment
Adverse Events
The safety will be assessed by the Number of adverse events, linked or not to the study product
Measured: After 4, 8, 12, 16, 20 and 24 weeks of treatment.
Severe Adverse Events
The safety will be assessed by the number of severe adverse events, linked or not to the study product
Measured: After 4, 8, 12, 16, 20 and 24 weeks of treatment.
Intestinal microbiota
Fecal microbiota composition
Measured: Baseline and 24 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2025
- Study start5 Aug 2026
- Primary completion5 Dec 2027 (estimated)
- Study completion5 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Obesity &Amp; OverweightStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective, double blind, randomized, monocentric, 2 parallel groups (1:1) study evaluating superiority probiotics over placebo in limiting the impairment in digestive quality of life over 24-week in patients with obesity initiating GLP-1 RA (semaglutide or tirzepatide) for weight control.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Emmanuel DISSE, PUPH, Principal investigator, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07213323
- Sponsor's protocol ID
- 69HCL25_0321
- Other IDs
- 2025-A01248-41
- Acronym
- PROBIO-GLP1
- Status last verified
- Aug 2026
- First submitted
- 18 Sep 2025
- Last updated
- 19 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No