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SIB
CompletedPhase 4Comparing Semaglutide Versus Placebo on Intestinal Barrier Function in Type 2 Diabetes Mellitus (SIB)
A Randomized Parallel Comparison of Semaglutide Versus Placebo on Intestinal Barrier Function in Type 2 Diabetes Mellitus (SIB)
Lead sponsor
Asset
Semaglutide
Subcutaneous · GLP-1 agonist
Listed sites
1
Recruiting sites
—
Enrollment
69
actual
Study population
Obesity / overweight, Type 2 diabetes
Key I/E criteria
•BMI ≥28•HbA1c ≤8%
Primary endpoint
•Differences in lactulose mannitol ratio (LMR) test as a measure of intestinal
Footprint
Where this trial recruits
Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.
Identifiers
Registered as
Timeline
Milestones
Assets
Investigational agents
Study populations
Who this study enrolls
Eligibility
Who can enroll
Inclusion criteria
1. Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial, except for protocol described pre-screening activities, which require a separate informed consent.
2. Male or female, age above or equal to 18 years at the time of signing informed consent.
3. Diagnosed with type 2 diabetes mellitus on metformin monotherapy
4. Hemoglobin A1c <8.0% (<64 mmol/mol) on screening day
5. Body mass index (BMI) ≥28 kg/m2
6. Low-grade inflammation, defined as elevated high sensitivity C-reactive protein (hs- CRP >1.0 and ≤10 mg/L). Impaired intestinal barrier function results in activation of inflammatory pathway; therefore, excluding subjects with no evidence of inflammation (hs-CRP ≤ 1 mg/L) will help to enrich our study population. Similar threshold for hs-CRP as a marker of "residual inflammatory risk" (29) has been previously used as an independent predictor of future vascular events (26, 30).
Exclusion criteria
1. Known or suspected hypersensitivity to trial product or related products.
2. Female who is pregnant, breast-feeding or intends to become pregnant or is of child- bearing potential and not using a highly effective contraceptive method.
3. Participation in any clinical trial of an approved or non-approved investigational medicinal product within 30 days before screening.
4. Any disorder, which in the investigator's opinion might jeopardize patient's safety or compliance with the protocol.
5. Any of the following: myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischemic attack (TIA) within the past 60 days prior to the day of screening.
6. Second anti-diabetic agent use within 3 months of screening.
7. Chronic kidney disease defined as eGFR < 30 mL/min/1.73 m2.
8. C-reactive protein (hs-CRP >10.0 mg/L) to eliminate patients with acute inflammatory process at the time of screening.
9. Any recent infection or antibiotic use within 3 weeks
10. Regular use (more than a week duration) of anti-inflammatory medication (steroid or NSAIDs) within 3 months of screening.
11. Regular use (more than a week duration) of any digestive health supplements, such as probiotics or prebiotics within 3 months screening.
12. Diagnosis of chronic intestinal inflammatory disease such as Crohn's disease, ulcerative colitis or irritable bowel syndrome.
13. Prior bariatric or bowel surgery
14. Heart failure presently classified as being in New York Heart Association (NYHA) Class IV.
15. Presence or history of malignant neoplasm within 5 years prior to the day of screening. Basal and squamous cell skin cancer and any carcinoma in-situ is allowed.
16. Personal or family history of multiple endocrine neoplasia type 2 (MEN2) or medullary thyroid carcinoma (MTC).
17. History of chronic pancreatitis or history of acute pancreatitis within 6 months of screening.
18. Chronic consumption of > 2 alcoholic standard drinks per day as defined by:
Endpoints (9)
What's being measured
Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.
Coverage by outcome category
Cardiometabolic biomarkers
1 endpointDifferences between treatment groups in plasma hs-CRP
Time frame:Week 8 (visit 4), Week 16 (visit 6)
hs-CRP, change
change from baseline, improvement
LOINC 30522-7
Safety / tolerability / PK
1 endpointDifferences between treatment groups in Fecal Calprotectin
Time frame:Week 8 (visit 4), Week 16 (visit 6)
change from baseline, descriptive
Other (unclassified)
7 endpointsDifferences in lactulose mannitol ratio (LMR) test as a measure of intestinal permeability between treatment groups
Time frame:Week 16 (visit 6)
ratio, descriptive
Differences between treatment groups in plasma LBP
Time frame:Week 8 (visit 4), Week 16 (visit 6)
change from baseline, descriptive
Differences between treatment groups in Serum zonulin
Time frame:Week 8 (visit 4), Week 16 (visit 6)
change from baseline, improvement
Differences between treatment groups in plasma IL-6
Time frame:Week 8 (visit 4), Week 16 (visit 6)
concentration, improvement
Differences between treatment groups in plasma IL-8
Time frame:Week 8 (visit 4), Week 16 (visit 6)
change from baseline, improvement
Differences between treatment groups in plasma TNFα
Time frame:Week 8 (visit 4), Week 16 (visit 6)
change from baseline, improvement
Exploratory: determine the effect of semaglutide as compared to placebo on intestinal microbiota in relation to changes in intestinal permeability and inflammatory markers
Time frame:Visit 6 (week 16)
descriptive
Publications (1)
Bibliography
Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.
Registry references + supporting bibliography
- Therapeutic advances in endocrinology and metabolism2023 (year)PMID37916028doi:10.1177/20420188231207348via pubmed nct search
Provenance
Sources
Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.