Cardiovascular outcome evidence in diabetes and metabolism, including MACE, heart failure, renal outcomes, lipid therapy, hypertension, and cardiometabolic risk reduction.
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.
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.
A secondary analysis finds beetroot supplements improve fatty acid and oxidant markers in coronary artery disease, but only short-term surrogates. PICO summary and commentary.
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 large D-Health trial finds monthly vitamin D does not prevent hypertension, high cholesterol, or type 2 diabetes in replete older adults. PICO summary and expert commentary.
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.
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