EMPEROR-Reduced confirmed that empagliflozin reduces cardiovascular death or hospitalisation for heart failure by 25% in patients with HFrEF irrespective of diabetes status, while also demonstrating a 50% reduction in a renal composite outcome and a markedly slower rate of eGFR decline, adding critical confirmatory evidence for SGLT2 inhibitors as standard-of-care in HFrEF.
Browsing: Landmark Trials in Endocrinology & Metabolism
A curated review of 52 landmark clinical trials in diabetes, obesity, metabolism, endocrinology, and cardiovascular disease — with expert commentary, key data tables, and clinical bottom lines.
The DAPA-HF trial demonstrated that dapagliflozin reduced the composite of worsening heart failure or cardiovascular death by 26% in patients with heart failure and reduced ejection fraction, with consistent benefit observed in both those with and without type 2 diabetes, establishing SGLT2 inhibition as a core therapy for HFrEF independent of glycaemic status.
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.