None listed
Conditions
Brief summary
Premature cardiovascular disease is the leading cause of death in people living with type 1 diabetes. Semaglutide, a long-acting glucagon-like peptide-1 receptor agonist, has been shown to reduce cardiovascular events and improve weight and glycaemia in type 2 diabetes. Semaglutide may offer cardioprotective and metabolic benefits in type 1 diabetes. Our study hypothesis is that semaglutide will reduce carotid femoral pulse wave velocity, a measure of arterial stiffness. Arterial stiffness has been shown to be an appropriate surrogate marker of cardiovascular risk in this population. Subjects will receive semaglutide 1.0mg weekly or matched placebo for 26 weeks. Potential mechanisms for metabolic changes will also be explored including insulin sensitivity determined by hyperinsulinaemic-euglycaemic clamp; and incretin and pancreatic hormone levels determined by mixed meal tolerance test. We will also study incretin and pancreatic hormones determined by mixed meal tolerance test in a group without diabetes to compare to the group with type 1 diabetes.
Interventions
Subcutaneous injection semaglutide, self-administered according to the following dose titration schedule: 0.25mg weekly for 4 weeks, 0.5mg weekly for 4 weeks, then 1mg weekly (or maximum tolerated dose).
Total duration post initiation of treatment 26 weeks (18 weeks at 1mg or maximum tolerated dose).
Sponsors
Garvan Institute of Medical Research
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
25 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Main study: 1. type 1 diabetes of greater than or equal to 2 years duration 2. body mass index greater than or equal to 25 kg/m2 3. HbA1c greater than or equal to 7.0% 4. at least one cardiovascular risk factor: - history of microalbuminuria [urinary albumin:creatinine ratio greater than 2.5 mg/mmol for males, greater than 3.5 mg/mmol for females] - hypertension [Blood pressure (BP) greater than 140/90mmHg] or anti-hypertensive treatment - hyperlipidemia [Total Cholesterol(TC):High Density Lipoprotein (HDL) ratio greater than 6] or lipid lowering therapy - current smoking Sub-study (Pancreatic hormones and carotid femoral pulse wave velocity only in people without diabetes to provide comparative data for baseline measures in type 1 diabetes group): 1. body mass index greater than or equal to 25 kg/m2
Exclusion criteria
Main and sub-study: 1. treatment with a GLP1 receptor agonist, metformin or SGLT2 inhibitor in the last 3 months 2. current or planned treatment with medications that affect glucose metabolism (i.e. glucocorticoids, antipsychotics, immunosuppressants) 3. previous or planned bariatric surgery during study period 4. diabetic ketoacidosis or severe hypoglycaemia in the last 12 months 5. eGFR less than 45 ml/min/1.73m2 6. evidence of significant liver disease (known cirrhosis, LFTs greater than 3x upper limit of normal) 7. known gastroparesis 8. history of pancreatitis or cholecystitis 9. pregnant, breastfeeding or female of childbearing potential not using adequate contraception 10. coronary event or stroke in the last 3 months 11. active or untreated proliferative diabetic retinopathy 12. personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2 13. previous adverse reaction to semaglutide necessitating discontinuation Sub-study: 1. diabetes mellitus
Outcome results
None listed