Semaglutide's kidney benefit held across 30,787 people with and without diabetes

Design

Prespecified pooled participant-level analysis of three randomised, placebo-controlled trials

Population

30,787 people with CKD or atherosclerotic cardiovascular disease, with and without diabetes

Primary outcome

Kidney composite: 50% eGFR fall, kidney failure, kidney-related or cardiovascular death

Effect

973 vs 1,134 events; HR 0.84 (95% CI 0.77 to 0.91)

This prespecified analysis pooled participant-level data from three placebo-controlled trials: SELECT, FLOW and SOUL. Participants had chronic kidney disease or atherosclerotic cardiovascular disease, and received semaglutide by subcutaneous injection at 1.0 or 2.4 mg weekly, or orally at 14 mg daily, on top of standard care. Mean follow-up ranged from about 40 to 48 months.

The primary composite was a persistent fall in eGFR of 50% or more, kidney failure, kidney-related death or cardiovascular death. It occurred 973 times with semaglutide and 1,134 times with placebo (HR 0.84, 95% CI 0.77 to 0.91). The narrower kidney composite, without cardiovascular death, also fell (347 vs 416 events; HR 0.80, 0.69 to 0.92). Safety outcomes were similar between groups, and serious adverse events were numerically fewer with semaglutide.

The pooled trials differed in population, dose and route, and the analysis was funded by the manufacturer. It adds weight to the case for a GLP-1 receptor agonist in people with cardio-kidney-metabolic disease, including those without diabetes, and suggests the benefit may not rest on glucose or weight alone. Existing guideline recommendations have not changed because of this paper.

• Consider semaglutide in people with type 2 diabetes and CKD or atherosclerotic disease, in line with current guidance.
• Record baseline eGFR and albuminuria so later kidney outcomes can be tracked.
• Continue an SGLT2 inhibitor or renin-angiotensin blockade where indicated; this analysis does not replace them.
• Discuss cost and access, since long-term GLP-1 therapy is expensive in India.
• The composite includes cardiovascular death, so read the narrower composite for purely kidney endpoints.

Why it matters

It extends semaglutide's kidney benefit beyond people with diabetes and CKD to a much wider cardiometabolic population.

Don't overread it

Pooling three trials with different populations, doses and routes does not make one uniform trial, and the sponsor funded the analysis.

The statistics, in plain English

A hazard ratio of 0.84 means a 16% lower rate of first events at any time during follow-up. The interval of 0.77 to 0.91 excludes 1, so the result is unlikely to be chance, but it applies to the pooled mix of trial populations, not equally to every patient.

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