The SELECT trial demonstrated that semaglutide 2.4 mg reduces 3-point MACE by 20% in overweight or obese adults with pre-existing cardiovascular disease and no diabetes, becoming the first obesity pharmacotherapy trial to demonstrate a hard cardiovascular endpoint benefit and establishing GLP-1 receptor agonism as a cardiovascular intervention in non-diabetic obesity.
Browsing: Cardiovascular Outcomes
The REWIND trial demonstrated that dulaglutide reduces 3-point MACE in a broad type 2 diabetes population of which 69% had no established cardiovascular disease, with a significant 24% reduction in nonfatal stroke and consistent renal benefit, extending GLP-1 receptor agonist cardiovascular protection into a primary prevention context.
The SUSTAIN-6 trial demonstrated that once-weekly semaglutide reduced 3-point MACE by 26% in high-cardiovascular-risk type 2 diabetes, driven primarily by a significant 39% reduction in nonfatal stroke, while identifying a retinopathy complication signal attributable to rapid glucose lowering in patients with pre-existing retinopathy.
The LEADER trial demonstrated that liraglutide significantly reduced 3-point MACE and cardiovascular mortality in patients with type 2 diabetes and high cardiovascular risk, becoming the first GLP-1 receptor agonist CVOT to demonstrate superiority and characterising an atherosclerotic rather than heart failure protection profile distinct from SGLT2 inhibitors.
The CREDENCE trial demonstrated that canagliflozin reduced the composite of end-stage kidney disease, doubling of serum creatinine, or renal or cardiovascular death by 30% in patients with type 2 diabetes and albuminuric chronic kidney disease, becoming the first dedicated renal outcomes trial to demonstrate that an SGLT2 inhibitor could substantially slow the progression of diabetic nephropathy.
The DECLARE-TIMI 58 trial demonstrated that dapagliflozin did not reduce 3-point MACE compared with placebo but significantly reduced the composite of cardiovascular death or hospitalisation for heart failure, driven entirely by a 27% reduction in heart failure hospitalisation, in the largest and most broadly representative SGLT2 inhibitor cardiovascular outcomes trial conducted to date.
The CANVAS Programme demonstrated that canagliflozin reduced major adverse cardiovascular events by 14% in patients with type 2 diabetes at high cardiovascular risk, but identified an approximately twofold increase in lower-extremity amputation risk, primarily at the toe or metatarsal level, requiring careful patient selection and monitoring.
The EMPA-REG OUTCOME trial demonstrated that empagliflozin reduced cardiovascular death by 38% and heart failure hospitalisation by 35% in patients with type 2 diabetes and established cardiovascular disease — the first glucose-lowering agent to show a mortality benefit in a cardiovascular outcomes trial.