← Trials/Trial dossier/NCT04979130

SIB

CompletedPhase 4

Comparing 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)

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 ≥28HbA1c ≤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

NCT IDNCT04979130
Org study ID21-2774

Timeline

Milestones

Study first posted2021-07-28actual
Study start2022-01-01actual
Primary completion2024-10-16actual
Study completion2024-10-16actual
Last update posted2025-03-20actual

Assets

Investigational agents

Study populations

Who this study enrolls

Obesity / overweightType 2 diabetes

Eligibility

Who can enroll

Minimum age18 Years
Maximum age89 Years
SexAll
Healthy volunteersNot accepted

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:

12 ounces of beer (5% alcohol content).
8 ounces of malt liquor (7% alcohol content).
5 ounces of wine (12% alcohol content).
1.5 ounces or a "shot" of 80-proof (40% alcohol content) distilled spirits or liquor (e.g., gin, rum, vodka, whiskey).

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

Other (unclassified)
7
Cardiometabolic biomarkers
1
Safety / tolerability / PK
1

Cardiometabolic biomarkers

1 endpoint
Secondary/protocol endpoint

Differences 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 endpoint
Secondary/protocol endpoint

Differences between treatment groups in Fecal Calprotectin

Time frame:Week 8 (visit 4), Week 16 (visit 6)

change from baseline, descriptive

Other (unclassified)

7 endpoints
Primary/protocol endpoint/low confidence

Differences in lactulose mannitol ratio (LMR) test as a measure of intestinal permeability between treatment groups

Time frame:Week 16 (visit 6)

ratio, descriptive

Secondary/protocol endpoint/low confidence

Differences between treatment groups in plasma LBP

Time frame:Week 8 (visit 4), Week 16 (visit 6)

change from baseline, descriptive

Secondary/protocol endpoint/low confidence

Differences between treatment groups in Serum zonulin

Time frame:Week 8 (visit 4), Week 16 (visit 6)

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Differences between treatment groups in plasma IL-6

Time frame:Week 8 (visit 4), Week 16 (visit 6)

concentration, improvement

Secondary/protocol endpoint/low confidence

Differences between treatment groups in plasma IL-8

Time frame:Week 8 (visit 4), Week 16 (visit 6)

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Differences between treatment groups in plasma TNFα

Time frame:Week 8 (visit 4), Week 16 (visit 6)

change from baseline, improvement

Other/protocol endpoint/low confidence

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

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2
Snapshot dateJuly 1, 2026
Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)
Results tableno registry results posted yet

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.