Empagliflozin's cardiovascular signal held across age, sex and income in over-65s

Design

Propensity-matched cohort study of Medicare claims (EMPRISE)

Population

Adults ≥65 with type 2 diabetes starting empagliflozin v DPP-4 inhibitor or GLP-1 receptor agonist

Primary outcome

MACE, heart failure hospitalisation and all-cause mortality

Effect

v DPP-4i: MACE HR 0.77, HHF HR 0.72, death HR 0.66; v GLP-1RA: HHF HR 0.88

The EMPRISE analysis used US Medicare claims from 2014 to 2020 to compare adults aged 65 and over with type 2 diabetes starting empagliflozin against propensity-matched starters of DPP-4 inhibitors or GLP-1 receptor agonists, published 21 September.

Against DPP-4 inhibitors, empagliflozin was associated with fewer major cardiovascular events (HR 0.77), fewer heart failure admissions (HR 0.72) and lower all-cause mortality (HR 0.66). Against GLP-1 receptor agonists, heart failure admissions were lower (HR 0.88). Relative effects did not differ by age band, sex, race or ethnicity, or socioeconomic factors. Absolute benefit was larger in people with established cardiovascular disease, and trended larger in those aged 75 and over.

The trials that established SGLT2 inhibitor benefit under-enrolled the oldest and the poorest. This real-world study cannot replace them, and residual confounding is likely — the mortality estimate in particular is larger than trials have shown. But it does not support withholding an SGLT2 inhibitor on age alone, and the absolute gain appears greatest in those with the most to lose.

• Age over 75 is not, on this evidence, a reason to withhold an SGLT2 inhibitor in type 2 diabetes.
• Prioritise an SGLT2 inhibitor where there is established cardiovascular disease, where absolute benefit was largest.
• Where heart failure risk dominates, an SGLT2 inhibitor may add more than a GLP-1 receptor agonist alone.
• Pair any start in a frail patient with sick-day rules and a diuretic review.

Why it matters

It challenges the reflex to hold back cardioprotective diabetes drugs in the oldest patients, who stand to gain most in absolute terms.

Don't overread it

This is observational claims data — the 34% lower mortality is an association and larger than randomised trials have shown.

The statistics, in plain English

Hazard ratios give relative change; the incidence rate differences give absolute change — about 18 fewer heart failure admissions per 1,000 person-years against DPP-4 inhibitors. The authors used 99.9% confidence intervals, a stricter standard than usual. Because this is observational, sicker or frailer people may have been steered to one drug, which matching reduces but cannot remove.

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