Empagliflozin's cardiovascular benefit did not fade with age or social background

Design

Propensity-matched cohort study using Medicare claims (EMPRISE)

Population

Adults aged 65 and over with type 2 diabetes starting empagliflozin, a DPP-4 inhibitor or a GLP-1 receptor agonist, 2014 to 2020

Primary outcome

Major adverse cardiovascular events, heart failure admission, all-cause mortality

Effect

vs DPP-4 inhibitors: MACE HR 0.77 (99.9% CI 0.69 to 0.85), HHF HR 0.72 (0.67 to 0.79); vs GLP-1 RA: HHF HR 0.88 (0.81 to 0.95)

The EMPRISE study used US Medicare claims from 2014 to 2020 to compare adults aged 65 and over with type 2 diabetes who started empagliflozin against propensity-matched people starting a DPP-4 inhibitor or a GLP-1 receptor agonist.

Against DPP-4 inhibitors, empagliflozin was associated with fewer major adverse cardiovascular events (HR 0.77, 99.9% CI 0.69 to 0.85), fewer heart failure admissions (HR 0.72, 0.67 to 0.79) and lower all-cause mortality (HR 0.66, 0.57 to 0.76). Against GLP-1 receptor agonists, the difference was in heart failure admissions only (HR 0.88, 0.81 to 0.95). Relative effects did not differ by age, sex, race, ethnicity or socioeconomic factors. Absolute benefit was larger in people with established cardiovascular disease, and numerically larger in those aged 75 and over.

The finding addresses a common hesitation: whether an older, frailer patient will gain as much from an SGLT2 inhibitor as trial participants did. In this real-world population, the answer was yes. Where a DPP-4 inhibitor is chosen mainly because it feels gentler in an older patient, it is worth reconsidering, with attention to volume status, genital hygiene and sick-day rules.

• Do not withhold an SGLT2 inhibitor from an older adult with type 2 diabetes on age alone.
• Review older patients on a DPP-4 inhibitor alone, especially those with cardiovascular disease or heart failure.
• Before starting, check eGFR, volume status, diuretic dose and ability to follow sick-day advice.
• In patients already on a GLP-1 receptor agonist, consider adding an SGLT2 inhibitor where heart failure risk is high.

Why it matters

Age is often the unspoken reason older patients stay on a DPP-4 inhibitor instead.

Don't overread it

Claims data cannot fully remove prescribing bias, so the size of the mortality association should not be taken at face value.

The statistics, in plain English

The authors used 99.9% confidence intervals, much stricter than the usual 95%, to reduce false positives across many subgroup comparisons; the main results stayed clearly below 1 even so. An incidence rate difference of −18.3 for heart failure admissions means about 18 fewer admissions per 1,000 person-years versus DPP-4 inhibitors. Because treatment was not randomised, some of this gap may reflect who gets prescribed which drug.

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