Comparing Semaglutide Versus Placebo on Intestinal Barrier Function in Type 2 Diabetes Mellitus (SIB)

Prior treatment

• Participation in any clinical trial of an approved or non-approved investigational medicinal product within 30 days before screening.
• 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.
• Regular use (more than a week duration) of anti-inflammatory medication (steroid or NSAIDs) within 3 months of screening.
• Prior bariatric or bowel surgery

Other illness

• Known or suspected hypersensitivity to trial product or related products.
• Any disorder, which in the investigator's opinion might jeopardize patient's safety or compliance with the protocol.
• Any recent infection or antibiotic use within 3 weeks
• Diagnosis of chronic intestinal inflammatory disease such as Crohn's disease, ulcerative colitis or irritable bowel syndrome.
• Heart failure presently classified as being in New York Heart Association (NYHA) Class IV.
• 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.
• Personal or family history of multiple endocrine neoplasia type 2 (MEN2) or medullary thyroid carcinoma (MTC).
• History of chronic pancreatitis or history of acute pancreatitis within 6 months of screening.

Lab values

• Chronic kidney disease defined as eGFR \< 30 mL/min/1.73 m2.

Other

• 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.
• Second anti-diabetic agent use within 3 months of screening.
• C-reactive protein (hs-CRP \>10.0 mg/L) to eliminate patients with acute inflammatory process at the time of screening.
• Regular use (more than a week duration) of any digestive health supplements, such as probiotics or prebiotics within 3 months screening.
• 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).

• 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.
• Male or female, age above or equal to 18 years at the time of signing informed consent.
• Diagnosed with type 2 diabetes mellitus on metformin monotherapy
• Hemoglobin A1c \<8.0% (\<64 mmol/mol) on screening day
• Body mass index (BMI) ≥28 kg/m2
• 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).