None listed
Conditions
Brief summary
Type 2 diabetes mellitus (T2DM) is a chronic disease, the prevalence of which is rapidly growing world-wide. As a result of historical concerns of the safety of available glucose-lowering therapies, cardiovascular outcome trials (CVOTs) were mandated by the Food and Drug Administration (FDA) in 2008 to ensure that new anti-diabetic therapies coming onto the market were safe from a cardiovascular perspective. Out of the recently studied drug classes, GLP-1 receptor agonists (GLP-1 RAs) and sodium-glucose co-transporter 2 (SGLT2) inhibitors have both shown to provide cardiovascular benefits, not just safety/non-inferiority compared to the more traditional glucose-lowering agents they have been compared to. Both are currently recommended in guidelines for use in patients with a cardiac history, however, it is not clear whether one would confer a greater benefit than the other in patients who have recently had an acute coronary syndrome (ACS), nor whether they can slow plaque progression, as a possible mechanism of their cardiovascular benefit. Given patients in Australia can only access one therapy at a time on the PBS, any information regarding their direct comparison in this patient population would be useful. This will be a prospective, randomised, open, blinded end-point (PROBE)-designed trial that will evaluate the effect of semaglutide and empagliflozin on coronary plaque, as assessed by computer tomography coronary angiography (CTCA) at baseline and following 12 months of treatment with either semaglutide or empagliflozin in participants with diabetes and known coronary artery disease who have presented with an acute coronary syndrome. We hypothesise that participants prescribed semaglutide will have a slower progression in coronary plaque development as compared with participants on empagliflozin.
Interventions
This will be a prospective, randomised, open, blinded end-point (PROBE)-designed trial.
Semaglutide (a glucagon-like peptide-1 receptor agonist (GLP-1 RA) will be self-administered subcutaneously by the patient (starting at 0.25mg/week, uptitrated on a monthly basis based on patient tolerance and at the direction of a physician, up to 1.0 mg/week as tolerated) in an open label manner.
Participants will undergo a baseline CT coronary angiogram (CTCA), continue on the treatment for 12 months,
This will be a prospective, randomised, open, blinded end-point (PROBE)-designed trial. Semaglutide (a glucagon-like peptide-1 receptor agonist (GLP-1 RA) will be self-administered subcutaneously by the patient (starting at 0.25mg/week, uptitrated on a monthly basis based on patient tolerance and at the direction of a physician, up to 1.0 mg/week as tolerated) in an open label manner. Participants will undergo a baseline CT coronary angiogram (CTCA), continue on the treatment for 12 months, and then undergo a repeat CTCA. Adherence will be assessed by patient report at 1, 2, 3, 6, 9, and 12 months.
Sponsors
South Australian Health and Medical Research Institute
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
- Hospitalisation with an acute coronary syndrome (as defined by the 2020 European Society of Cardiology (ESC) Guidelines for the Management of Acute Coronary Syndromes), where participant has undergone invasive coronary angiography and is left with residual atherosclerotic stenoses in one or more coronary arteries of at least 20% severity that will be left for medical management with no intention to revascularise by stenting or bypass grafting in the next 12 months - Previous or new (in hospital) diagnosis of type 2 diabetes - No contraindication to glucagon-like peptide-1 receptor agonists (GLP-1 RA) or sodium glucose co-transporter-2 (SGLT2) inhibitor usage (see key exclusion criteria) - Eligible to use either GLP-1 RA or SGLT2 inhibitor as per PBS criteria (in summary, patients must have type 2 diabetes, and be on treatment with metformin and/or sulfonylurea as tolerated, and have a HbA1c >7%) - Willing to use injectable medication - Willingness to be on birth control for women of childbearing age or established post-menopausal - Participants are required to have undergone screening, enrolment, baseline imaging and randomisation and drug initiation within 30 days of their index admission for their acute coronary syndrome
Exclusion criteria
- Contraindication to GLP-1 RA use, including history of pancreatitis (acute or chronic), and established retinopathy - Contraindication to SGLT2 inhibitor use, including recurrent genitourinary infections, and history of ketoacidosis - Known history of a clinically significant gastric emptying abnormality, such as severe gastroparesis or gastric outlet obstruction, or being planned for bariatric surgery within the next 12 months - Left ventricular ejection fraction <=35% or New York Heart Association (NYHA) class IV heart failure - A personal or family history of medullary thyroid carcinoma, or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN2) - Known type 1 diabetes - Prior/known intolerance of GLP-1 receptor agonists or SGLT2 inhibitors - Concurrent DPP4 use or use within the 2 weeks prior to randomisation occurring - Dialysis or estimated glomerular filtration rate (eGFR) <30 ml/min/1.73m2 - Previous or planned coronary artery bypass grafting - Pregnant women or women planning pregnancy in the following 12 months - Life expectancy <1year - Contraindications to CT coronary angiography - Concurrent enrolment in another placebo-controlled trial or within 30 days of finishing another trial - Enrolment and participation in another trial involving ionising radiation in the last 12 months
Outcome results
None listed