Effect of Liraglutide on Diastolic Dysfunction on Cardiac MRI in Type 2 Diabetes Patients

This is an interventional treatment trial for Diabetes Mellitus Type 2 Read More

Inclusion Criteria:

• Male or female patient fully capable of informed consent
• Informed consent
• Age 18-80 years (both years inclusive)
• T2DM diagnosed at least 3 months prior to visit 0
• NYHA class I-III at visit 0
• E/e* ≥ 9 or e* (lateral) ≤10 cm/sec, or both
• LVEF > 50%
• LVEDV/BSA < 97 ml/m2
• Stable on heart medication for 6 weeks prior to randomisation
• Stable on antidiabetic treatment for 30 days prior to randomisation
• T2DM must be either treated with one or more oral anti-diabetic drugs or treated with human NPH-insulin or long-acting insulin analogue, alone or in combination with oral drugs

Exclusion Criteria:

• Lack of consent.
• NYHA class IV
• Type 1 diabetes mellitus
• Incretin-based therapy (GLP-1 receptor agonists; exenatide, liraglutide or other and DPP-IV inhibitors) within 30 days prior to randomisation (visit 1)
• Glitazon therapy within 30 days prior to randomisation (visit 1)
• Hypertension with inadequate blood pressure control: Systolic blood pressure > 140 mmHg and/or diastolic blood pressure >85 mmHg*
• Supine systolic blood pressure <85 mmHg measured at visit 0
• Significant valvular heart disease
• Hypertrophic cardiomyopathy, ARVC/D, non-compaction or amyloidosis
• Myocardial infarction, unstable angina, angina on exertion (≥CCS class 2) or coronary revascularization within 3 months prior to randomisation (visit 1)
• Hospitalisation due to incompensated heart disease within 30 days to randomisation (visit 1)
• HbA1c >10% at visit 0
• eGFR< 60 ml/min/1,73 m2 at visit 0
• Liver disease with aspartate aminotransferase/alanine aminotransferase >3 times upper limit of normal measured at visit 0**
• Hypokalaemia (P-potassium <3.5 mmol/L) or hyperkalaemia (P-potassium >5.5 mmol/L) measured at visit 0**
• Anaemia (haemoglobin <6.5 mmol/L) measured at visit 0**
• Conditions that may be associated with changes in markers of fibroses or collagen turnover (eg. on-going or active rheumatological disease requiring anti-inflammatory agents, immunosuppression, pulmonary fibrosis, active cancer)
• Prolonged use (> 2 weeks) of glucocorticoids or NSAIDs within 2 weeks prior to visit 0
• Women of childbearing potential who are not on acceptable contraception. See below.
• Pregnant or breastfeeding women
• Cancer (except basal cell skin cancer or squamous cell skin cancer) unless complete remission for ≥ 5 years
• Alcohol/drug abuse
• Chronic or previous acute pancreatitis
• History of thyroid adenoma or carcinoma
• Inflammatory bowel disease
• Clinical signs of diabetic gastroparesis
• ICD/pacemaker or other contraindications to MRI scan
• Severe claustrophobia
• Atrial fibrillation
• Contraindications to glycopyrrolate: closed-angle glaucoma, prostate hyperplasia, tachycardia, bladder atony, cardia insufficiency, non-congenital pylorus stenosis and gastroparesis
• Known or suspected hypersensitivity to trial product or related products
• Current participation in any other clinical intervention trial
• Receipt of an investigational drug with 30 days prior to visit 0

• Other concominant disease or treatment that according to investigator's assessment makes the patient unsuitable for participation in the study

  • Measured twice at visit 0. In case of elevation, an ambulatory (24-hour) blood pressure will be performed, and the result of this will be conclusive

    • Measured at visit 0 with the possibility of one repeat analysis within a week, and the last measured value will be conclusive.