Impact of Glucagon on Physical Capacity and Metabolism

Prior treatment

• Substance abuse (illegal drugs)

Other illness

• History of acute coronary syndrome or percutaneous coronary intervention/bypass surgery or cerebrovascular event (e.g. stroke) within the last 6 months
• Known allergies or intolerances in connection with study medication
• Severe or high-grade heart valve stenosis and/or insufficiency
• Known significant MASLD with advanced fibrosis (grade III - IV) and/or liver cirrhosis and/or alcohol-induced liver disease
• Known active malignant disease and/or known active underlying inflammatory or infectious disease
• Type I diabetes mellitus or insulin-dependent type II diabetes mellitus

Lab values

• Left ventricular ejection fraction < 45%
• Known severely impaired renal function (eGFR <30ml/min according to CKD-EPI formula)
• Physical/physical limitations that impair mobility or performance o E.g. underlying neuromuscular diseases, anaemia (anaemia < 12 g/dl), acute and/or chronic orthopaedic diseases that restrict physical mobility/performance, congenital heart defects

Other

• Existing contraindications for carrying out a cardiopulmonary performance test
• Pregnancy
• Inability to give informed consent/ inability to make independent decisions
• Employment relationship with the sponsor or the conducting clinic
• Simultaneous participation in another clinical trial or intervention study or participation in a clinical trial or intervention study within the last 3 months
• Obesity per magna (BMI >40 kg/m2)

• Age between 18 - 80 years and able to understand the requirements of the study and willing to provide signed informed consent for voluntary participation in the study
• Patients with clinically confirmed heart failure with preserved ejection fraction (HFpEF) by: a) Symptoms and signs of heart failure b) Left ventricular ejection fraction ≥ 45% c) Objective signs of structural and/or functional cardiac dysfunction consistent with the presence of left ventricular diastolic dysfunction/elevated left ventricular filling pressures, including elevated serum natriuretic peptides
• Metabolic associated steatotic liver disease (MASLD) without higher-level fibrosis (F3) confirmed by o Transient elastography  Elasticity (E) ≥ 8 - And  At least stetosis I-II (CAP ≥248 - ≤ 280 dB/m) o Presence of at least 1 cardiometabolic criterion  BMI > 25 kg/m2  Fasting BG > 100 mg/dl or 2h postprandial >140mg/dl or already diagnosed type 2 diabetes mellitus  RR >130/85mmHg or under antihypertensive therapy  Fasting triglycerides > 150 mg/dl or under therapy  HDL < 40 mg/dl (m) and < 50 mg/dl (w)