Blood Glucose Response After Oral Intake of Lactulose in Mildly Constipated Patients With Diabetes Mellitus Type 2

Inclusion criteria

• Patients with non-insulin requiring diabetes mellitus type 2 treated with diet and oral antidiabetics and/or Glucagon-like Peptide 1 receptor agonists
• Age: 18-75 years
• Female and male
• Caucasian
• HbA1c ≤ 7.5 %
• Stable treatment, i.e. no change in diabetes mellitus related medication within the last 3 months
• Mild functional constipation according to modified Rome IV criteria fulfilled for the last 3 months with symptom onset at least 6 months before study start defined as:

• approx. 3-5 bowel movements per week,
• of which 1-2 usually cause discomfort e.g., straining, lumpy or hard stools, sensation of incomplete evacuation or anorectal obstructions/blockage
• Availability and presence in the trial unit for approx. 4 hours/ week for 4 weeks
• Women of childbearing potential must be using a medically approved method of contraception OR women must be postmenopausal for at least 12 months prior to study entry
• Signed informed consent form

Exclusion criteria

• Fasting blood glucose <4.4 mmol/L (<80 mg/dL) or >10 mmol/L (>180 mg/dL) (capillary)
• BMI <18.5 kg/m² or ≥35 kg/m²
• Change in body weight ≥10 % within the last 3 months
• Smoker
• Major medical or surgical event requiring hospitalization within the last 3 months
• Acute gastrointestinal diseases including diarrhea and/or vomiting within the last 2 weeks
• Presence of disease or intake of drug(s) / supplements other than antidiabetic treatment influencing digestion and absorption of carbohydrates or bowel habits (intake of laxatives in general allowed with exception see next criterion) (dietary / supplementary fibres allowed if stable dose since 1 month before study start)
• Not willing to abstain from laxatives 2 days before the visits 1-4 and up to 24h after visits 1-4
• Use of following medication/ supplementation within the last 4 weeks and during the study:

• Intake of medications other than antidiabetic treatment known to affect glucose tolerance e.g., steroids, protease inhibitors or antipsychotics;
• Intake of prebiotics or probiotics
• Chronic intake of substances affecting blood coagulation (e.g. acetylic acid (100 mg as standard prophylactic treatment allowed when dose is stable 1 month prior to screening), anticoagulants, diuretics, thiazides (diuretics and thiazides allowed e.g. for hypertension treatment when dose is stable 1 month prior to screening)), which in the investigator's opinion would impact patient safety
• Severe liver, renal or cardiac disease
• Hereditary problems of galactose or fructose intolerance, lactase deficiency or glucose-galactose malabsorption
• Suspicion of alcohol abuse (defined as an average daily intake of more than one litre of beer per day or equivalent amount of alcohol in other beverages) or drug abuse
• Known or suspected allergy to the investigational drug(s) or other components of the study drug(s)
• Acute inflammatory bowel disease (ulcerative colitis, Crohn's disease), gastrointestinal obstruction or subocclusive syndrome, perforations or risk of perforation in gastrointestinal tract, abdominal pain of undetermined cause
• Known history of human immunodeficiency virus (HIV), hepatitis B and/or C
• Pregnancy, lactation
• Clinically relevant findings as established by medical history, physical examination, clinical laboratory and/or vital signs
• Participation in another interventional study with an investigational drug or an investigational medical device within 30 days prior to start of study or during the study