EMPA-REG OUTCOME — Empagliflozin in High-Risk T2D

Design

EMPA-REG OUTCOME randomised 7,020 patients with T2D and established cardiovascular disease to empagliflozin (10 mg or 25 mg) versus placebo added to standard care, median follow-up ~3 years.

Findings

• Primary composite (CV death, non-fatal MI, non-fatal stroke): 14% relative reduction (HR 0.86, p=0.04 for superiority).
• Cardiovascular death: 38% relative reduction.
• All-cause mortality: 32% relative reduction.
• Hospitalisation for heart failure: 35% relative reduction.
• Renal outcomes: 39% relative reduction in incident or worsening nephropathy.

Why it matters

The magnitude of cardiovascular-death reduction was unprecedented for a diabetes drug and emerged within months, far too quickly to be explained by glucose lowering. Subsequent trials (CANVAS canagliflozin, DECLARE-TIMI 58 dapagliflozin, EMPEROR-Preserved/Reduced, DAPA-HF, DAPA-CKD) confirmed and extended these findings:

• SGLT2 inhibitors benefit heart-failure patients with and without diabetes.
• They slow CKD progression in diabetic and non-diabetic CKD.
• They reduce cardiovascular death across multiple high-risk populations.

Likely mechanisms

Beyond glucose lowering: natriuresis and reduced preload, ketogenesis and cardiac fuel-economy benefit, anti-inflammatory effects, reduced glomerular hyperfiltration, uric-acid reduction.

Related entries

SGLT2 inhibitors, Heart failure, Chronic kidney disease.