Impact of Hypoglycaemia in Patients With Diabetes Mellitus Type 2 on Platelet Activation

Inclusion Criteria

• Male or female aged 18-64 years (both inclusive) at the time of signing informed consent
• Subjects diagnosed with type 2 diabetes (diagnosed regarding world health organization [WHO] criteria) and on stable treatment for a period of 90 days prior to screening with metformin as monotherapy or diet only. Stable is defined as unchanged dose
• Body mass index (BMI) between 20.0 and 35.0 kg/m2 (both inclusive)
• HbA1c between 43 and 64 mmol/mol (6.0% - 8.0%) (both inclusive)
• No use of platelet inhibiting therapy (e.g. aspirin, clopidogrel, ticagrelor, prasugrel)

Exclusion Criteria

• All other forms of diabetes (type 1 diabetes, gestational diabetes) than type 2 diabetes mellitus
• Treatment with any glucose lowering agent(s) other than metformin in a period of 60 days before screening. An exception is short-term treatment (≤ 7 days in total) with insulin due to intercurrent illness
• Impaired hypoglycaemic awareness determined at the discretion of the investigator
• Medical history of arrhythmia as atrial fibrillation, atrial flutter, atrioventricular dissociation disorders or ventricular arrhythmias
• Previously known cardiovascular disease and / or past cardiovascular events, or past episodes of a congestive heart failure syndrome (NYHA II - NYHA IV)
• Severe hypoglycaemic event requiring third party help in the last 6 months
• Known allergy to human insulin or dextrose solution
• Clinically significant abnormal haematology, biochemistry, lipids, hormones, coagulation or urinalysis
• Uncontrolled hypertension defined as resting blood pressure at screening (after resting for 5 min, measured in sitting position) outside the range of 90-160 mmHg for systolic or 50-100 mmHg for diastolic
• Chronic liver failure with severe liver dysfunction as assessed by the investigator
• Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) levels > 3x upper Limit of normal (ULN)
• estimated Glomerular Filtration Rate (eGFR) <45 ml/min/1,73 m2
• Any musculoskeletal disorders holding back from stay in bed in a lying position during the time of the clamp experiments
• Treatment with beta-blockers, antiarrhythmic agents or neuroleptic drugs
• Active smoker or intake of illicit substances
• Regular intake of nonsteroidal anti-inflammatory drugs (NSAIDs)
• Any mental disorders or psychiatric conditions which may interfere with understanding or conduction of study related procedures
• Females of child bearing potential without adequate contraceptive methods (i.e. sterilisation, intrauterine device, vasectomised partner; or medical history of hysterectomy)