SGLT2 inhibitors after 75: no excess harm against DPP-4 inhibitors

Design

Population-based active-comparator new-user cohort, propensity weighted

Population

6,286 adults aged 75 or older with type 2 diabetes in British Columbia

Primary outcome

Infection, ketoacidosis, kidney injury, falls, fractures, hospitalisation

Effect

Kidney injury HR 0.76 (0.60–0.95); hospitalisation HR 0.87 (0.77–0.98)

A population-based cohort from British Columbia compared new users aged 75 or older starting an SGLT2 inhibitor (4,997, median age 79) or a DPP-4 inhibitor (1,289, median age 82) between 2021 and 2023, weighting for measured differences.

Starting an SGLT2 inhibitor was associated with less acute kidney injury (HR 0.76, 95% CI 0.60–0.95) and fewer hospitalisations from any cause (HR 0.87, 0.77–0.98). Infection rates did not differ. There was no clear difference in ketoacidosis, falls or fractures, but the intervals were wide enough to include either benefit or harm.

Older adults are the people most often denied an SGLT2 inhibitor for fear of dehydration, falls and genital infection, and the trials enrolled few of them. This does not replace trial evidence, but it removes much of the case for withholding these drugs on age alone. Choose by frailty, intake and the cardiorenal indication, not the birth year.

• Do not withhold an SGLT2 inhibitor on age alone when there is a cardiorenal indication.
• Assess frailty, oral intake and continence before starting, and review at four to six weeks.
• Reduce diuretic doses where volume depletion is a concern when starting.
• Counsel on genital hygiene and sick-day rules at the first prescription.
• Keep ketoacidosis and fracture risk in mind, as this study could not exclude a small increase.

Why it matters

This challenges the habit of reaching for a DPP-4 inhibitor simply because the patient is old.

Don't overread it

Rare harms such as ketoacidosis were too imprecise to rule out; this is an association, not a trial.

The statistics, in plain English

HR 0.76 for kidney injury means about a quarter lower rate, with the interval excluding no effect. For ketoacidosis and fractures the intervals crossed 1.0, so the study cannot tell us whether risk is higher, lower or the same.

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